Top 25 pharma and biopharma report.
04 Merck & Co.
08 Johnson & Johnson
12 Eli Lilly & Co.
14 Bristol-Myers Squibb
15 Boehringer Ingelheim
17 Novo Nordisk
20 Merck KGaA
25 Daiichi Sankyo
TOP 25 PHARMA AND BIOPHARMA COMPANIES (Based on 2015 Sales, in $U.S. Millions) 1. Novartis $49,414 2. Pfizer $48,851 3. Sanofi $40,486 4. Merck & Co. $39,498 5, Roche $37,667 6. GlaxoSmithKline $35,463 7. Gilead $32,639 8. Johnson & Johnson $31,430 9. AstraZeneca $24,708 10. AbbVie $22,859 11, Amgen $21,662 12. Eli Lilly & Co. $19,958 13. Teva $19,652 14. Bristol-Myers Squibb $16,560 15. Boehringer Ingelheim $16,167 16. Takeda $16,068 17. Novo Nordisk $15,801 18. Allergan $15,071 19. Bayer $15,017 20. Merck KGaA $14,034 21. Otsuka $11,993 22. Biogen $10,764 23. Mylan $9,363 24. Celgene $9,256 25. Daiichi Sankyo $8,770 01 NOVARTIS Headquarters: Basel, Switzerland twitter.com/novartis www.novartis.com HEADCOUNT: 119,000 YEAR ESTABLISHED: 1996 REVENUES: $49,414 (-5%) PHARMA REVENUES: $30,445 (-4%) NET INCOME: $17,794 (+73%) R&D: $8,935 (-2%) DRUGS APPROVED DRUG INDICATION Afinitor advanced gastrointestinal (GI) and lung neuroendocrine tumors Revolade chronic immune (idiopathic) thrombocyto penic purpura Cosentyx ankylosing spondylitis and psoriatic arthritis Entresto heart failure Farydak multiple myeloma Tafinlar and Mekinist melanoma Odomzo advanced basal cell carcinoma Promacta/Revolade pediatric immune thrombocytopenia DRUGS PENDING DRUG INDICATION osentyx ankylosing spondylitis, psoriatic arthritis, nonradiographic axial spondyloarthritis Arzerra chronic lymphocytic leukemia (extended treatment), chronic lymphocytic leukemia (relapse), non-Hodgkin's lymphoma Afinitor/Votubia nonfunctioning Gl and lung neuroendocrine tumors, tuberous sclerosis complex seizures Jadenu Exjade iron overload film coated tablet PHASE IIB AND BEYOND DRUG INDICATION BKM120 breast cancer BYL719 breast cancer LCI699 Cushing's disease PKC412 acute myeloid leukemia Tasigna chronic myeloid leukemia Zykadia ALK9+ advanced nonsmall cell lung cancer Votrient renal cell carcinoma (adjuvant) ACZ885 cardiovascular events RLX030 acute heart failure Entresto chronic heart failure with preserved ejection fraction, postacute myocardial infarction QMF149 asthma JM112 immune disorders llaris hereditary periodic fevers BAF312 secondary progressive multiple sclerosis Gilenya chronic inflammatory demyelinating polyradiculoneuropathy AMG 334 migraine BYM338 sporadic inclusion body myositis EXE844b anti-infective OAP030 neovascular agerelated macular degeneration RTH258 wet agerelated macular degeneration EARLY RESEARCH PROJECTS DRUG INDICATION ABL001 chronic myeloid leukemia ASB183 solid and hematologic tumors LJM716 solid tumors PIM447 hematologic tumors DRUGS COMING OFF PATENT DRUG INDICATION YEAR Gilenya autoimmune disease 2017 Exjade iron chelation 2017 Starlix blood glucose lowering agent 2017 Lotrel cardiovascular disorders 2017 Exforge hypertension 2017 Diovan hypertension 2017 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Gleevec/Glivec oncology $4,658 -2% Gilenya autoimmune disease $2,776 12% Lucentis age-related macular degeneration $2,060 -16% Tasigna chronic myeloid leukemia $1,632 7% Sandostatin acromegaly $1,630 -1% Afinitor oncology $1,607 2% Diovan hypertension $1,284 -45% Galvus diabetes $1,140 -7% Exforge hypertension $1,047 -25% Exjade iron chelation $917 -1%
Novartis moved into 2015 having acquired GlaxoSmithKline's (GSK) oncology products, solidifying its position as a global leader in cancer treatments. The two companies also merged their over-the-counter (OTC) businesses into a joint venture that is one of the world's largest consumer healthcare companies, 36.5% owned by Novartis. At the same time, Novartis sold its vaccines business, excluding the influenza business, to GSK. The influenza vaccines business was sold to CSL Limited while the animal health business was sold to Eli Lilly.
Altogether Novartis reported sales of $49.4 billion in 2015. The pharmaceuticals division was responsible for $30.4 billion of total revenue followed by the eye care business with $9.8 billion. The generics business brought up the rear with $9.2 billion of revenue.
As this issue went to press, Novartis unveiled plans to restructure its pharmaceuticals division by creating two business units--Novartis Pharmaceuticals and Novartis Oncology. From July 1, 2016 Novartis will continue to have three focused, customer-facing divisions: Innovative Medicines (formerly the Novartis Pharmaceuticals division), which will include the new Novartis Pharmaceuticals and Novartis Oncology business units; Sandoz, the generics and biosimilar division, which includes the retail generics, anti-infectives and biopharmaceuticals franchises; and Alcon, the eye care devices division, which includes the surgical and vision care franchises.
Paul Hudson has been appointed chief executive officer, Novartis Pharmaceuticals, and Bruno Strigini will become chief executive officer, Novartis Oncology. Both will report directly to Joseph Jimenez, chief executive officer, Novartis. With these changes, David Epstein, division head and chief executive officer, Novartis Pharmaceuticals, has decided to leave the company. The new structure reflects the importance of oncology to the company following the integration of the oncology assets acquired from GSK mentioned above.
GROWTH PRODUCTS LEAD THE CHARGE
In today's pharmaceutical environment, growth products are a vital component to renew product portfolios, while at the same time helping to offset the impact of patent expirations. Across Novartis' divisions, its portfolio of growth products continued to support performance in 2015. Sales of growth products increased 17% to $16.6 billion, or 34% of net sales. In the pharma division, sales of growth products increased 33% and accounted for 44% of net sales, up from 36% in 2014.
Pharmaceutical growth products in 2015 included Gilenya ($2.8 billion, +21%), an oral therapy for multiple sclerosis; Tasigna ($1.6 billion, +16%), a treatment for chronic myeloid leukemia; and Afinitor ($1.6 billion, +10%), a treatment for several types of cancer.
In the generics division, sales of biopharmaceuticals, including biosimilar follow-on versions of complex biologic drugs, surged 39% to $772 million globally.
Geographically, efforts to expand in emerging growth markets such as those in Asia, Africa and Latin America continued to deliver results for Novartis, although growth moderated as overall economic activity slowed in China, Brazil, India and elsewhere. Net sales in emerging markets rose 7% to $12.4 billion, led by Turkey, up 14%, and Brazil, up 12%.
To increase efficiency, an ongoing effort begun in 2010 to optimize its global manufacturing network continued to take shape. In 2015, Novartis announced plans to exit Sandoz manufacturing sites in Frankfurt and Gerlingen, Germany, as well as in Turbhe, India. It also closed a pharmaceuticals division facility in Resende, Brazil, divested an Alcon site in Kaysersberg France, as well as a pharmaceutical site in Taboao da Serra, Brazil, and announced the downsizing of a pharmaceuticals division site in Ringaskiddy, Ireland. To date, 25 sites in Novartis' continuing operations have been, or are being restructured or divested.
INNOVATION ACROSS THE BOARD
Novartis made significant progress in research and development in 2015, with 20 major approvals in key markets and 14 major submissions.
On the cardiovascular front, Novartis had notable success during the year with the approval in the U.S. and EU of Entresto (formerly LCZ696) to treat chronic heart failure with reduced ejection fraction, a condition where the heart muscle does not contract effectively and less oxygen-rich blood is pumped around the body. Entresto is the first new drug in decades to treat this form of heart failure. It is also the only heart failure drug to show a significant mortality benefit in a head-to-head trial against the existing best treatment, enalapril.
In oncology, new cancer drugs gained regulatory approval in 2015. Zykadia, for patients with non-small cell lung cancer, was approved in the EU, a year after its U.S approval. The treatment is from a new class of medicines known as anaplastic lymphoma kinase (ALK) inhibitors.
In September, Novartis received EU approval for Tafinlar + Mekinist, the first combination therapy approved for patients with unresectable or metastatic melanoma with a BRAF V600 mutation--the most aggressive form of skin cancer and one associated with low survival rates. This approval followed two Phase III trials in which the Tafinlar + Mekinist combination showed significant overall survival benefit. The FDA approved the Tafinlar + Mekinist combination in late 2015.
The FDA and the European Commission also approved Novartis' first-in-class multiple myeloma drug Farydak (panobinostat), shown in trials to boost progression-free survival by about 7.8 months.
The company also reached major development milestones during the year with promising pipeline products, including CTL019 in non-Hodgkin's lymphoma, a difficult-to-treat disease. CTL019, a personalized cell therapy for cancer, is being developed with the University of Pennsylvania.
In immunology and dermatology, in early 2015, Novartis received approval in the U.S. and EU for Cosentyx to treat moderate to severe plaque psoriasis. Cosentyx is the first approved human monoclonal antibody that selectively binds to circulating interleukin-17A, which plays an important role in driving the body's immune response in several disorders. In total, 50 countries have approved Cosentyx for the treatment of moderate-tosevere plaque psoriasis. In November, Cosentyx was approved in Europe for the treatment of psoriatic arthritis and ankylosing spondylitis. Novaartis received FDA approval in January 2016.
For biosimilars, Sandoz received FDA approval in March for Zarxio (filgrastim), the first biosimilar approved in the U.S. under the new biosimilar pathway created in the Biologies Price Competition and Innovation Act of 2009. The drug, which stimulates white blood cell production in some cancer patients undergoing chemotherapy, is called Zarzio in Europe and is a biosimilar to Neupogen from Amgen. The FDA and the European Medicines Agency accepted an application for etanercept, a biosimilar to Amgen's Enbrel for several autoimmune diseases, including rheumatoid arthritis and psoriatic arthritis. The FDA also accepted an application for pegfilgrastim, a biosimilar to Amgen's Neulasta, used against infections in patients receiving chemotherapy.
EXPANDING THE PIPELINE
In June 2015 Novartis expanded its neuroscience portfolio with novel angiotensin II type 2 receptor antagonist for the treatment of chronic pain when it acquired Spinifex Pharmaceuticals, a U.S. and Australian privately held development stage company, focused on developing a peripheral approach to treat neuropathic pain.
Novartis bought Melbourne-based Spinifex for $312 million. The acquisition is centered on Spinifex's lead candidate EMA401, a novel angiotensin II type 2 (AT2) receptor antagonist, being developed as a potential first-in-class oral treatment for chronic pain, particularly neuropathic pain, without central nervous system (CNS) side effects.
Positive results from Spinifex's Phase II clinical trial of EMA401 in PHN, a painful condition that develops in some people following herpes zoster (shingles), have been published. Novartis will continue the development of EMA401 and is planning to initiate Phase lib clinical trials in patients with PHN or PDN. Novartis also intends to build on these two key indications and pursue a broad peripheral neuropathic pain (PNP) label for EMA401.
In October 2015 Novartis broadened its immuno-oncology pipeline with the acquisition of Admune Therapeutics and licensing agreements with XOMA and Palobiofarma.
With four candidates currently in clinical trials and five more agents expected to enter the clinic by the end of 2016, Novartis has rapidly built a robust portfolio of programs focused on stimulating the body's immune system to combat cancers that includes novel checkpoint inhibitors, chimeric antigen receptor T-cell (CART) technology, myeloid cell targeting agents, and STING agonists. Currently Novartis' myeloid cell targeting program (MCS-110) and checkpoint inhibitors targeting PD-1 (PDR001), LAG-3 (LAG525), are in Phase I clinical trials. The CART program (CTL019) is in Phase II clinical trials. The anti-TIM-3 program (MGB453) is expected to enter the clinic by the end of 2015 and a STING agonist (MIW815), through collaboration with Aduro Biotech, and GITR agonist are progressing toward first-in-human clinical trials in 2016.
The acquisition of Admune adds an IL-15 agonist program currently in Phase I clinical trials for metastatic cancer. The licensing agreement with Palobiofarma gives Novartis development and commercialization rights to PBF-509, an adenosine receptor antagonist currently in Phase I clinical trials for non-small cell lung cancer. The agreement with XOMA gives Novartis development and commercialization rights to XOMA's TGF-beta antibody programs. All three programs will be explored as monotherapies and in combination with therapies in Novartis' immuno-oncology and targeted therapy portfolios.
In preclinical studies, IL-15 therapies have been shown to activate CD8+, CD4+ memory T cells and Natural Killer (NK) cells that play a critical role in stimulating the immune system. Adenosine and TGFfi both drive immune suppression in the tumor microenvironment, which allows cancer cells to escape immune surveillance, making inhibition of these two pathways an attractive next-generation immuno-oncology approach.
NOVARTIS, AMGEN ENTER NEUROSCIENCE ALLIANCE
Aims to advance Alzheimer's and migraine programs
During the year Novartis and Amgen entered a collaboration in the areas of Alzheimer's disease and migraine using Novartis' differentiated and genetically validated Alzheimer's program directed at genetically predisposed individuals at risk. The collaboration also allows Amgen to focus on the commercialization of its migraine programs in the U.S., Canada and Japan, while leveraging Novartis' commercial capabilities in neuroscience throughout Europe and other markets.
The agreement combines each company's BACE (beta-site APP-cleaving enzyme-1) programs targeting Alzheimer's disease into a global co-commercialization and co-development arrangement. Novartis' Phase 1/2a BACE inhibitor (CNP520) will be the lead molecule and each company's preclinical BACE inhibitor programs will be potential follow-ons.
Amgen is responsible for upfront and milestone payments, and will be responsible for disproportions! R&D costs for an agreed-upon period followed by a 50/50 cost and profit share arrangement. Amgen was the first company to clone the BACE gene and subsequent genetic validation of the BACE target has been confirmed by Amgen subsidiary deCODE Genetics.
Novartis receives global co-development rights and commercial rights outside of the U.S., Canada and Japan to investigative molecules in Amgen's migraine portfolio. This includes AMG 334 in Phase III and AMG 301 in Phase I, as well as an option to commercialize an additional early-stage Amgen molecule. Novartis will fund disproportions! amounts of global R&D expenses for the migraine programs and pay Amgen royalties on sales.
02 PFIZER, INC. Headquarters: New York, NY twitter.com@pfizer_news www.pfizer.com HEADCOUNT: 73,800 YEAR ESTABLISHED: 1849 REVENUES: $48,851 (-2%) BIOPHARMA REVENUES: $45,708 billion (-5%) NET INCOME: $6,960 (-24%) R&D: $7,690 (-8%) DRUGS APPROVED DRUG INDICATION QuilliChew ER ADHD Sayana Press injectable contraceptive Rapamune lymphangioleiomyomatosis DRUGS PENDING DRUG INDICATION Ibrance HR+, HER2- metastatic breast cancer Xalkori ROS1-positive metastatic non-small cell lung cancer Xeljanz severe chronic plaque psoriasis PHASE IIB AND BEYOND DRUG INDICATION avelumab non-small cell lung cancer, gastric cancer, ovarian cancer, renal cell carcinoma, uro-thelial cancer Ertugliflozin type 2 diabetes Ibrance early breast cancer MOD-4023 adult growth hormone deficiency bococizumab/RN316 hyperlipidemia Rivipansel vaso-occlusive crisis associated with sickle cell disease Tanezumab OA signs and symptoms, chronic low back pain, cancer pain Vyndaqel cardiomyopathy PF-06834635 metastatic merkel cell carcinoma Coagulation Factor IX hemophilia Dekavil rheumatoid arthritis glasdegib acute myeloid leukemia lorlatinib non-small cell lung cancer EARLY RESEARCH PROJECTS DRUG INDICATION PF-06282999 acute coronary syndrome PF-06293620 type 2 diabetes PF-06480605 Crohn's disease PF-06650833 lupus PF-04958242 schizophrenia PF-05251749 Alzheimer's disease PF-06669571 cognitive disorder PF-04136309 pancreatic cancer PF-06647020 cancer PF-06801591 cancer immunotherapy PF-04447943 sickle cell anemia PF-06741086 hemophilia PF-05402536 smoking cessation PF-06753512 prostate cancer PF-05206388 age-related macular degeneration DRUGS COMING OFF PATENT DRUG INDICATION YEAR Spiriva COPD 2016 Vfend antifungal 2016 Zyvox bacterial infections 2016 Relpax migraine 2016 Tygacil bacterial infections 2016 Effexor XR anxiety 2017 Lyrica epilepsy, neuropathy 2018 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Prevnar family pneumoccal vaccine $6,245 40% Lyrica epilepsy, neuropathy $4,839 -6% Enbrel rheumatoid arthritis $3,333 -13% Lipitor cholesterol $1,860 -10% Viagra erectile dysfunction $1,708 1% Sutent cancer $1,120 -5% Premarln menopause $1,018 -5% Norvasc hypertention $991 -11% Zyvox bacterial infections $883 -35% Celebrex pain $830 -69%
Pfizer was at the center of the biggest story to rock the pharma world in 2015 when it was announced in November that it and Allergan would merge in a $160 billion deal, catapulting the combined company past Novartis atop the pharma leader boards.
But, the inversion deal didn't happen. It was called off at the last minute after a change in U.S. tax law.
If it had gone through Allergan would have acquired Pfizer and the two businesses would be combined under Allergan pic, to later be renamed Pfizer pic. Although on paper Allergan would be buying Pfizer, Pfizer would have retained control of the company with Pfizer stockholders holding 56% of the combined company and Allergan shareholders owning 44%.
In addition, the combined company was expected to maintain Allergan's headquarters in Ireland creating a huge tax incentive for Pfizer. The U.S. corporate tax rate is 35%, while Ireland's is just 12.5%. Pfizer's global operational headquarters would be in New York and its principal executive offices in Ireland.
However, the U.S. Treasury Department introduced rules aimed at reducing the incentives for companies to carry out inversions and taking advantage of another nation's lower tax rate.
According to Pfizer, the change in rules was impactful enough to reduce the advantages expected from the merger. Pfizer paid Allergan $150 million to cover expenses related to calling off the deal.
If it still has its eyes set on becoming the largest pharma giant in the world, they're going to have to wait for the time being. That being said, 2015 wasn't just about the failed Allergan deal.
Pfizer gained a portfolio of biosimilars and sterile injectable products when it bought Hospira for $17 billion. Hospira has built a reputation as a leading provider of injectable drugs and infusion technologies, as well as biosimilars. The global market value for both generic sterile injectables and biosimilars is expected to grow, estimated to be $70 billion and $20 billion in 2020, respectively.
The acquisition expands Pfizer's portfolio of sterile injectable pharmaceuticals with Hospira's generic sterile injectables product line, including acute care and oncology injectables, with a number of differentiated presentations. Pfizer's branded sterile injectables include anti-infectives, anti-inflammatories and cytotoxics. Pfizer also plans to employ its commercial capabilities, global scale, and scientific and development capabilities to significantly expand Hospira's portfolio of marketed biosimilars, including Retacrit to treat anemia associated with chemotherapy, and Nivestim, a biosimilar version of filgrastim (GCSF), to treat neutropenia.
In another deal, Pfizer acquired a minority equity interest in AM-Pharma and secured an exclusive option to acquire the company. AM-Pharma is a privately held Dutch biopharma company focused on the development of recombinant human alkaline phosphatase (recAP) for inflammatory diseases.
Pfizer made an upfront payment of $87.5 million for the minority interest and exclusive option, with additional potential payments of up to $512.5 million upon the potential launch of any product from this agreement.
Pfizer may exercise the option upon completion of a Phase II trial of recAP in the treatment of Acute Kidney Injury (AKI) related to sepsis, for which there are no drugs currently approved. Results from the Phase II trial are expected in 2H16.
During the year Pfizer also acquired a controlling interest in Redvax GmbH, a spin-off from Redbiotec AG, a privately held Swiss biopharma company, gaining access to a preclinical human cytomegalovirus (CMV) vaccine candidate, as well as intellectual property and a technology platform related to a second, undisclosed vaccine program. CMV is a herpes virus, infecting 50-90% of the adult population, with a majority remaining asymptomatic. A large segment of young adults, especially women of childbearing age, are at high risk of CMV infection during pregnancy and of passing the infection on to the unborn child. One out of every five children born with CMV infection may experience hearing loss and severe neurologic disorders.
In another transaction, Pfizer entered into an agreement with GSK to acquire its quadrivalent meningitis ACWY vaccines, Nimenrix and Mencevax, for a total consideration of approximately $130 million. Nimenrix is a single dose meningococcal ACWY-TT (tetanus toxoid) conjugated vaccine designed to protect against Neisseria meningitidis, an uncommon but highly contagious disease that can lead to disability and death. It was launched three years ago and is indicated for all age groups one year and older. Nimenrix is currently approved in 61 countries, with registrations under review in another 18 countries across Africa, Asia, Eastern Europe and the Middle East. Mencevax is a single-dose meningococcal ACWY unconjugated polysaccharide vaccine used to control outbreaks of meningococcal infection and for travelers to countries where the disease is endemic. It's indicated for use across all age groups from two years of age, and is currently registered and approved in 79 countries across Africa, Asia, Australia, Europe, Latin America, Middle East and New Zealand.
SEGMENT AND PRODUCT PERFORMANCE
Total revenues for Pfizer were $48.9 billion in 2015, driven by the performance of several key products in developed markets, including the continued strong uptake of Prevnar 13, Ibrance, Eliquis, Lyrica and Xeljanz. Direct product sales of more than $1 billion were reported for seven products in 2015.
Pfizer operates through two distinct businesses: an Innovative Products business and an Established Products business. The Innovative Products business is composed of two operating segments--the Global Innovative Pharmaceutical segment (GIP) and the Global Vaccines, Oncology and Consumer Healthcare (VOC).The Established Products business consists of the Global Established Pharmaceutical segment (GEP).
GIP recorded sales of $13.9 billion in 2015. Key therapeutic areas include inflammation/immunologycardiovascular/metabolic, neuroscience/pain and rare diseases and include leading brands, such as Xeljanz, Eliquis, Lyrica (U.S. and Japan), Enbrel (outside the U.S. and Canada) andViagra (U.S. and Canada).
VOC netted $12.8 billion in sales and focuses on the development and commercialization of vaccines and products for oncology and consumer healthcare manufacturing and marketing several well known, over-the-counter (OTC) products..
GEP is the largest of Pfizer's business areas with $21.5 billion in revenue and includes legacy brands that have lost or will soon lose market exclusivity in both developed and emerging markets, branded generics, generic sterile injectable products, biosimilars and infusion systems. Hospira and its commercial operations are now included within GEP.
Geographically, in the U.S., revenues increased $2.6 billion, or 14%, in 2015, compared to 2014, reflecting, among other things the performance of several key products, including Prevnar 13 primarily in adults, up approximately $1.9 billion; Ibrance, which was launched in the U.S. in February 2015, up approximately $720 million; as well as Lyrica (GIP), Eliquis, Xeljanz, Viagra (GIP) and Nexium 24HR, collectively up approximately $1.0 billion in 2015.
Performance was offset by losses of exclusivity and associated multi-source generic competition for Celebrex in the U.S. in December 2014, down approximately $1.6 billion in 2015; the loss of exclusivity for Zyvox and Rapamune, as well as the termination of the Spiriva co-promotion collaboration, collectively, down approximately $620 million in 2015; and the performance of Lipitor and BeneFIX, collectively, down approximately $160 million in 2015.
In Pfizer's international markets, revenues decreased $3.4 billion, or 11%. Total share of international revenues also dropped in the year from 62% the prior year to 56% in 2015.
Emerging markets represented continued strong operational growth primarily from the Innovative Products business, including Prevenar and Enbrel, among other products, and Lipitor, up approximately $600 million in 2015; higher revenues in developed markets for Eliquis and Lyrica (GIP), as well as from vaccines acquired in December 2014 from Baxter in Europe, collectively, up approximately $590 million in 2015.
Business was offset by lower revenues in developed markets for Lyrica (GEP), Celebrex, Inspra and Viagra (GEP) as a result of the loss of exclusivity, as well as the performance of Lipitor and Norvasc in developed markets, and Zosyn/Tazocin in emerging markets, collectively down approximately $1.0 billion in 2015.
During the year Pfizer and Adaptive Biotechnologies entered into a translational research collaboration to leverage next-gen sequencing of the adaptive immune system to advance Pfizer's immuno-oncology pipeline. The companies will combine drug development and platform technology biomarker expertise to identify patients who may benefit from immunotherapy.
Adaptive's immunosequencing platform measures the patient's immune-cell repertoire, providing a translational tool to accelerate Pfizer's immuno-oncology biomarker and drug development programs. Adaptive will work with Pfizer to apply its platform technology, bioinformatics capability, and scientific expertise.
Merck KGaA and Pfizer entered into a collaboration Syndax Pharmaceuticals to evaluate avelumab, an investigational fully human anti-PD-L1 IgGl monoclonal antibody, in combination with Syndax's entinostat, an investigational oral small molecule that targets immune regulatory cells (myeloid-derived suppressor cells and regulatory T-cells), in patients with heavily pre-treat ed, recurrent ovarian cancer. Avelumab is currently being investigated across a broad range of tumor types under the alliance between Merck KGaA and Pfizer. This is an exclusive agreement with Syndax to study the combination of these two compounds in ovarian cancer. Syndax will be responsible for conducting the Phase Ib/II trial.
Pfizer and BIND Therapeutics extended the terms of their global collaboration through to create Accurins that optimize two of Pfizer's targeted oncology drugs. The collaboration was established in April 2013 under which Bind employs its nanomedicine platform to develop targeted and programmable therapeutics known as Accurins.
Pfizer has the exclusive option to pursue development and commercialization of the Accurins selected, at which point Pfizer will have responsibility for development and commercialization of the selected Accurins. Both companies will work together on preclinical research. BIND has the potential to receive as much as $88.5 million based on specified development and regulatory milestones, as well as $110 million for specified commercial events and royalties for each Accurin commercialized.
PFIZER CONSOLIDATES RESEARCH LABS
Will create a single Pfizer Cambridge campus for discovery and development efforts
Pfizer has unveiled plans to expand its lease agreement with a subsidiary of Massachusetts Institute of Technology, creating a unified Pfizer campus in Kendall Square. With this expansion, Pfizer has leased the full 500,000 square feet at 610 Main Street in Kendall Square. This space will continue to house the R&D activities that relocated to 610 Main Street in 2014, and will enable the consolidation of Pfizer's three other leased spaces in Cambridge into the one campus.
This most recent lease addition secures an added 130,000 square feet of space for potential expansion in the future and will be available for sub-tenancy in 2017. Once the three remote sites are consolidated, 610 Main Street will house approximately 1,000 Pfizer employees.
Pfizer's R&D efforts in Cambridge will continue to focus on rare diseases, cardiovascular and metabolic disease, inflammation and immunology, neuroscience, and advanced biotherapeutic technologies. The expanded 370,000-plus square foot KSQ research center will help foster a strong laboratory culture, with experimentation and collaboration in the heart of Cambridge's Kendall Square innovation hub, featuring state-of-the-art labs and an open design to help foster breakthrough productivity and innovation that will potentially advance Pfizer's pipeline.
The Pfizer Cambridge campus provides more laboratory capabilities in proximity to one another; opportunities for collaborations between Pfizer and smaller start-ups and/or biotechs; the ability to coalesce functions from across Pfizer R&D currently spread across Cambridge; and close proximity to new companies.
03 SANOFI Headquarters: Paris, France twitter.com/sanofi www.sanofi.com HEADCOUNT: 115,631 YEAR ESTABLISHED: 2004 REVENUES: $40,486 (-1%) NET INCOME: $8,053 (+8%) R&D: $5,863 (-5%) DRUGS APPROVED DRUG INDICATION Dengvaxia tetravalent dengue vaccine Praluent hypercholesterolemia Toujeo type 1 and type 2 diabetes DRUGS PENDING DRUG INDICATION sarilumab moderate-to-severe rheumatoid arthritis PR5i DTP-HepB-Polio-Hib lixisenatide type 2 diabetes LixiLan type 2 diabetes VaxiGrip QIV IM quadrivalent inactivated influenza vaccine PHASE IIB AND BEYOND DRUG INDICATION SAR342434 type 1 and type 2 diabetes sotagliflozin type 1 diabetes sarilumab rheumatoid arthritis dupilumab atopic dermatitis, asthma patisiran familial amyloidotic polyneuropathy revusiran familial amyloidotic cardiomyopathy Jevtana metastatic prostate cancer (IL) Clostridium difficile toxoid vaccine VaxiGrip QIV IM influenza vaccine (6-35 months) Pediatric pentavalent DTP-Polio-Hib vaccine Men Quad TT 2nd generation meningococcal ACYW conjugate vaccine EARLY RESEARCH PROJECTS DRUG INDICATION GZ402668 relapsing multiple sclerosis GZ389988 osteoarthritis SAR425899 type 2 diabetes SAR566658 solid tumors SAR439684 cancer GZ402666 Pompe disease SAR339375 Alport syndrome fitusiran hemophilia SAR228810 Alzheimer's disease SAR439152 hypertrophic cardiomyopathy Streptococcus meningitis & pneumonia pneumonia vaccine Herpes Simplex HSV-2 vaccine Virus Type 2 UshStat Usher syndrome 1B DRUGS COMING OFF PATENT DRUG INDICATION YEAR Eloxatin cancer 2016 Nasacort AQ allergy 2016 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Lantus diabetes $6,981 -9% Plavix heart attack, stroke $2,107 -7% Lovenox thrombosis $1,878 -9% Polio/Pertussis/ vaccines $1,473 5% Hib Vaccines Influenza vaccines $1,444 1% Vaccines Renvela/ hypocalcemia $1,022 23% Renagel Aprovel/Avapro hypertention $832 -6% Cerezyme Gaucher disease $827 -5% Myozyme/ Pompe disease $710 8% Lumizyme Meningitis/ vaccines $671 21% Pneumonia Vaccines
After a bit of a turbulent close to 2014 that saw the ouster of former chief executive officer Chris Viehbacher, who was fired amid whistleblower lawsuit claims that the company was involved in a kickback scheme, Sanofi brought in Olivier Brandicourt as the new chief executive to right the ship. With nearly 30 years experience in the pharma industry and the former chair of Bayer Healthcare's management board, Mr. Brandicourt led the French pharma giant to $40.5 billion in revenue in 2015.
Pharmaceutical segment sales rose by 7.5% and includes Genzyme operations as well as a broad range of prescription medicines, generic medicines, and consumer health products.
Sales for the diabetes division were down nearly 7% mainly due to lower sales of Lantus in the U.S., where sales dropped 17%. Outside the U.S., the division posted 9% growth driven by emerging markets, which were up 16%. Western Europe posted more modest sales growth of 3% due to the entry of a biosimilar of insulin glargine into the market in the second half of the year. As a result, sales for the glargine franchise, which includes Lantus and Toujeo, a new-generation basal insulin launched in 2015, fell by 8.5%.
In the oncology business sales were down 1.9%. The company says solid performances from Jevtana and Mozobil were offset by the impact of generic versions of Taxotere in Japan. Sales of Jevtana were up 9.5% driven by a strong performance in the U.S. and Japan, where the product was launched in September 2014. Mozobil sales were up 16% mainly on sales growth in the U.S. Taxotere saw net sales fall sharply by 22% because the product is facing competition from generics in emerging markets and in Japan.
The Genzyme business posted sales growth of nearly 30% driven by a solid performance from the multiple sclerosis franchise. Aubagio sales surged by 78% while the ongoing launch of Lemtrada continued to yield very positive results.
Sales for the consumer health care business rose by 3% on strong sales from Allegra OTC in the U.S. following the launch of a new formulation. The generics business posted sales growth of 7.6% in 2015 driven by increased sales of the authorized generic of Lovenox.
In 2015, net sales for the Vaccines segment, which includes the Sanofi Pasteur MSD joint venture with Merck, were up 19%.
Within the vaccines segment sales of Polio/Pertussis/Hib vaccines rose by 8% boosted by the performances of Pentaxim and Hexaxim. Sales in emerging markets grew strongly by 33% due to sales of Pentaxim and polio vaccines in China.
Sales of influenza vaccines rose by 2% with strong growth in the U.S., while in emerging markets sales declined by 15%. Sales of meningitis/pneumonia vaccines climbed 17%. Adult booster vaccines net sales increased by 10%.
In 2015 Sanofi announced a number of strategic alliances designed to drive product innovation and business growth. On the cancer front, Regeneron Pharmaceuticals and Sanofi entered into a immuno-oncology global collaboration to discover, develop and commercialize new antibody cancer treatments. The companies will jointly develop a programmed cell death protein 1 (PD-1) inhibitor currently in Phase I and plan to initiate trials in 2016 with new preclinical therapeutic candidates. Regeneron received a $640 million upfront, and the companies will invest $1 billion for discovery through proof of concept/Phase IIa of monotherapy and novel combinations of immuno-oncology antibody candidates to be funded 25% by Regeneron ($250 million) and 75% by Sanofi ($750 million). The companies have also committed to equally fund an additional $650 million for development of REGN2810, a PD-1 inhibitor. Also, Sanofi will pay Regeneron a one-time milestone of $375 million should sales of a PD-1 product and any other collaboration antibody exceed $2 billion in any consecutive 12-month period.
In another cancer deal, Sanofi and BioNTech A.G. entered into a multi-year exclusive collaboration and license agreement to discover and develop as many as five cancer immunotherapies, each consisting of a mixture of synthetic messenger RNAs (mRNAs).
BioNTech received $60 million in upfront and near-term milestone payments, and is eligible to receive more than $300 million in development, regulatory and commercial milestones per product, as well as royalties on sales. Also, BioNTech has the option to co-develop and co-commercialize two of the five mRNA therapeutics products with Sanofi in the EU and U.S.
Leveraging Sanofi's global oncology footprint and scientific expertise, BioNTech will combine the use of its mRNA technology platform to develop immune-stimulating pharmaceuticals. As part of this effort, BioNTech will utilize its mRNA formulation technology, which enables targeted mRNA delivery in vivo, to generate novel cancer immunotherapies. BioNTech will also supply part of the mRNA material needed for development activities from its GMP manufacturing unit.
Also in the field of cancer research, Evotec AG and Apeiron Biologies AG, a biotech company with a focus on immunological approaches to treat cancer, formed a strategic collaboration with Sanofi to develop novel small molecule-based cancer immunotherapies.
This collaboration includes major research and development efforts to advance a first-in-class small molecule approach to treat solid and haematopoietic cancers by enhancing the anti-tumor activity of human lymphocytes. Based on Evotec's technological expertise and Apeiron Biologies' immunological know-how, the collaboration will also focus on the identification of novel small molecule hits and their targets for next-generation therapies in immuno-oncology, which are expected to complement the current offerings of checkpoint inhibitors.
The collaboration is set up as an initiative to support long-term pipeline building for Evotec, Apeiron Biologies and Sanofi. All three companies will make contributions to this collaboration in terms of scientific expertise, technological platforms and resources.
The agreement triggers two years of research payments for Evotec and Apeiron Biologies with the opportunity to receive preclinical, clinical, regulatory and commercial milestones which could total over 200 million [euro] as well as royalties upon commercialization.
Evotec and Sanofi also formed a collaboration in the field of diabetes. The goal of this collaboration is to develop a beta cell replacement therapy based on functional human beta cells derived from human stem cells. In addition, Sanofi and Evotec will also use human beta cells for high-throughput drug screening to identify beta cell active small molecules or biologies. The agreement triggers an upfront payment of 3 million [euro], potential preclinical, clinical, regulatory and commercial milestones, which could total over 300 million [million] as well as significant royalties and research payments.
Also in diabetes, Sanofi and Lexicon Pharmaceuticals entered into a collaboration and license agreement for the development and commercialization of sotagliflozin, an investigational new oral dual inhibitor of sodium-glucose cotransporters 1 and 2 (SGLT-1 and SGLT-2), which could be a potential treatment option for people with diabetes. The developmental medicine sotagliflozin (LX4211) is currently being studied in two Phase III trials in type 1 diabetes, which are expected to report top-line results during the second half of 2016. Phase III trials in type 2 diabetes are expected to begin in 2016.
Sotagliflozin could have the potential to become an important option among oral anti-diabetic medicines and provide a strong rationale for the further investigation of this compound as a treatment for people with diabetes. Lexicon received an upfront payment of $300 million and is eligible to receive development, regulatory and sales milestone payments of up to $1.4 billion. Lexicon is also entitled to tiered, escalating double digit percentage royalties on net sales of sotagliflozin.
During the year Adimab entered a multi-target discovery and optimization collaboration with Sanofi to use its platform to generate bispecific molecules against multiple targets. Sanofi has the right to develop and commercialize any resulting therapeutic antibodies and bispecifics. Adimab receives an undisclosed upfront payment, research fees and technical milestones. Also, for each target, Sanofi will have the option to exclusively license antibodies and bispecifics generate during the collaboration, at which point, Adimab would receive license fees, clinical milestones and royalties on product sales.
Sanofi and Boehringer Ingelheim entered an alliance to extend Sanofi's manufacturing capacity network for therapeutic monoclonal antibodies. Boehringer's cell culture operations will provide contract manufacturing capacities to support the production of Sanofi's biologies pipeline. Under the agreement, Sanofi will have access to Boehringer's capabilities to transfer and manufacture therapeutic monoclonal antibodies for global market supply. Initial product transfers will begin in early 2015.
Sanofi also entered into a collaboration with Catalent Pharma Solutions to implement Catalent's SMARTag technology in the development of next generation antibody-drug conjugates (ADCs). Catalent will develop site-specifically modified antibody conjugates using Sanofi's antibodies, enabling Sanofi to evaluate site selective payload conjugation in order to enhance ADC pharmacokinetics, efficacy and safety. The collaboration involves teams at Sanofi and Catalent's facility in Emeryville, CA.
SANOFI REVEALS NEW GLOBAL BUSINESS UNIT STRUCTURE
Three new global business units for general medicines and emerging markets, specialty care, and diabetes and cardiovascular
In July of last year Sanofi released plans to create five global business units: General Medicines and Emerging Markets; Specialty Care; Diabetes and Cardiovascular; Sanofi Pasteur; and Merial.
"The new organization simplifies and focuses Sanofi to optimize growth," said Olivier Brandicourt, chief executive officer, Sanofi. This is a necessary step for ensuring that Sanofi's new medicines and vaccines continue to build on our heritage of providing innovative healthcare therapies."
The General Medicines and Emerging Markets global business unit is led by Peter Guenter and consists of Sanofi's established products, generics, consumer healthcare, and all pharmaceutical businesses in emerging markets.
The Specialty Care global business unit, called Sanofi Genzyme, is led by David Meeker and consists of Sanofi's medicines in rare diseases, multiple sclerosis, oncology and immunology, including the two, investigational biologies, sarilumab and dupilumab.
The Diabetes and Cardiovascular global business unit is led by Pascale Witz and consists of Sanofi's diabetes care medicines as well as cardiovascular, including Praluent (alirocumab), which is currently under review by the U.S. FDA and the European Medicines Agency (EMA).
Sanofi Pasteur and Merial are both global business units and will continue to manage their current portfolios of vaccines and animal health products. Olivier Charmeil will continue to lead Sanofi Pasteur and Carsten Hellmann will continue to lead Merial.
The composition of the executive committee remains unchanged and the leadership roles announced above became effective January 1, 2016.
04 MERCK Headquarters: Whitehouse Station, NJ twitter.com/Merck www.merck.com HEADCOUNT: 68,000 YEAR ESTABLISHED: 1889 REVENUES: $39,498 (-6%) PHARMA REVENUES: $34,782 (-3%) NET INCOME: $4,442 (-63%) R&D: $6,704 (-7%) DRUGS APPROVED DRUG INDICATION Emend for injection chemotherapy induced nausea and vomiting, pediatric Zepatier chronic hepatitis C virus Keytruda advanced melanoma, non-small cell lung cancer Bridion reversal of neuromuscular blockade DRUGS PENDING DRUG INDICATION Zinplava Clostridium difficile Infection Keytruda head and neck cancer V419 pediatric hexavalent combination vaccine PHASE IIB AND BEYOND DRUG INDICATION verubecestat Alzheimer's disease anacetrapib atherosclerosis relebactam bacterial infection Keytruda bladder cancer, multiple myeloma, breast cancer, colorectal cancer letermovir CMV prophylaxis in transplant patients MK-8342B contraception ertuglifiozin+metformin diabetes V920 Ebola vaccine Sivextro HABP/VABP bacterial pneumonia V212 herpes zoster doravirine HIV odanacatib osteoporosis EARLY RESEARCH PROJECTS DRUG INDICATION rVSV-EBOV Ebola vaccine V160 cytomegalovirus V114 pneumococcal infections MSC1936369B solid tumors, cancer MK-3475 clear cell renal carcinoma OTX015/MK-8628 cancer DRUGS COMING OFF PATENT DRUG INDICATION YEAR Zetia cholesterol 2016 Cancidas antifungal 2016 Ivanz infections 2016 Cubicin antibiotic 2016 Asmanex Twisthaler asthma 2017 Dulera asthma 2017 Nasonex allergic rhinitis 2017 Emend chemotherapy induced 2018 nausea and vomiting TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Januvia/Janumet diabetes, obesity $6,014 0% Zetia/Vytorin cholesterol $3,777 -9% Gardasil HPV vaccine $1,908 10% Remicade rheumatoid arthritis $1,794 -24% Isentress HIV/AIDS $1,511 -10% Proquad, MMR, vaccines $1,505 8% and Varivax Cubicin antibiotic $1,127 n/a Singular asthma $931 -15% Nasonex allergic rhinitis $858 -22% Keytruda cancer $566 n/a
Due to the ongoing impacts of the loss of market exclusivity for several products, worldwide sales for Merck dropped 6% to $39.5 billion in 2015. However, the company reported that these unfavorable impacts were partially offset by volume growth in oncology, diabetes, women's health and vaccine products.
Sales in the U.S. were $17.5 billion, an increase of 3%, driven primarily by the acquisition of Cubist Pharmaceuticals, as well as higher sales of the company's lung cancer treatment Keytruda, Gardasil/Gardasil 9, Januvia/Janumet, Zetia, a cholesterol modifying medicine, and higher third-party manufacturing sales.
International sales declined 13% to $22 billion in 2015 due mostly to unfavorable foreign exchange across all regions. Lower sales in the pharmaceutical segment reflected declines in Europe and Japan, partially offset by growth in the emerging markets. Sales in Europe declined 19% to $7.7 billion because of bad foreign exchange and lower sales of Remicade, as well as lower sales of products for the treatment of HCV and from product divestitures and ongoing generic erosion. Sales in Japan declined 23% to $2.6 billion. Again aside from foreign exchange, the sales decline was largely driven by product divestitures and the ongoing impacts of the loss of market exclusivity for several products, including Cozaar and Hyzaar, treatments for hypertension, as well as lower sales of Peglntron and Januvia.
Emerging market revenue also dropped but not as sharply as Europe and Japan. Sales were $7.3 billion, a decline of 6%.Total international sales for Merck represented 56% of total sales in 2015.
ON THE M&A FRONT
At the tail end of 2014 Merck struck a major deal when it acquired Cubist Pharmaceuticals for $9.5 billion. Cubist develops therapies to treat infections caused by a broad range of increasingly drug-resistant bacteria. Its antibiotic Cubicin is the only approved once-a-day therapy for both S. aureus bacteremia and complicated skin and skin structure infections (cSSSI). In addition, Cubist has a late-stage pipeline of anti-infective medicines, including Zerbaxa, which at the time of the deal was pending FDA approval. Merck said the deal added more than $1 billion of revenue to its 2015 base.
In another transaction, Merck acquired cCAM Biotherapeutics, a privately held biopharmaceutical company focused on the discovery and development of novel cancer immunotherapies. Merck made an upfront payment of $95 million, with an additional $510 million to be paid when certain clinical development, regulatory and commercial milestones are met.
The acquisition provides Merck with several early immunotherapy candidates including cCAM Biotherapeutics' lead pipeline candidate, CM-24--a novel monoclonal antibody (mAb) targeting the immune checkpoint protein CEACAM1 that is currently being evaluated in a Phase I study for the treatment of advanced or recurrent malignancies, including melanoma, non-small-cell lung, bladder, gastric, colorectal, and ovarian cancers. Based on the transaction, cCAM Biotherapeutics, headquartered in Israel, will become a wholly owned subsidiary of Merck and continue to advance the development of CM-24 in its ongoing Phase I clinical trial. cCam was originally established under the Israeli Office of Chief Scientist's incubators program.
At the very beginning of 2016 Merck acquired IOmet Pharma, a drug discovery company focused on the development of medicines for the treatment of cancer, with a particular emphasis on the fields of cancer immunotherapy and cancer metabolism.
During the year Merck entered into a multi-year collaboration with NGM Biopharmaceuticals to research, discover, develop and commercialize novel biologic therapies across a wide range of therapeutic areas. The collaboration includes multiple drug candidates currently in preclinical development at NGM, including NP201 being evaluated for the treatment of diabetes, obesity and nonalcoholic steatohepatitis (NASH). NGM will lead R&D for existing preclinical candidates and pursue other discovery stage programs. Merck will have the option to license any resulting NGM programs following human proof of concept trials for global product development and commercialization.
NGM received $94 million upfront and Merck purchased a 15% equity stake in NGM for $106 million. Merck said it will commit as much as $250 million to fund NGM's efforts under the initial five-year term of the collaboration, with the potential for additional funding.
Prior to Merck initiating a Phase III study for a licensed program, NGM may elect to receive milestone and royalty payments or to participate in a global cost and revenue share arrangement of as much as 50%. NGM also has the option to participate in the co-promotion of any co-funded program in the U.S. NGM's lead program, NGM282, currently in clinical development for primary biliary cirrhosis (PBC) and NASH, are not subject to the option under the Merck collaboration.
ADVANCING THE PIPELINE
During 2015, Merck continued to execute its research and development focused-strategy, advancing its pipeline and commercial portfolio.
Merck is focusing its research efforts on the therapeutic areas that it believes can make the most impact on addressing critical areas of unmet medical need, such as cancer, hepatitis C, cardiometabolic disease, resistant microbial infection and Alzheimer's disease.
During 2015, the company continued to make strides in its late-stage pipeline. MK-6072, bezlotoxumab, is an investigational antitoxin for the prevention of Clostridium difficile (C. difficile) infection recurrence that is currently under review with the FDA and the European Medicines Agency (EMA). MK-1293, an insulin glargine candidate for the treatment of patients with type 1 and type 2 diabetes being developed in a collaboration, is also under review in the EU, as is Zepatier. Keytruda is under review in the EU for the treatment of NSCLC.
In addition to Phase III programs for Keytruda in the therapeutic areas of bladder, breast, colorectal, gastric, head and neck, multiple myeloma, and esophageal cancers, the Company also has more than 10 candidates in Phase III clinical development in its core therapeutic areas, as well as other areas with significant potential, including MK-3102, omarigliptin, an investigational once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor in development for the treatment of adults with type 2 diabetes; MK-0822, odanacatib, an oral, once-weekly investigational treatment for patients with osteoporosis; MK-8835, ertugliflozin, an investigational oral sodium glucose cotransporter-2 (SGLT2) inhibitor being evaluated alone and in combination with Januvia (sitagliptin) and metformin for the treatment of type 2 diabetes; and MK-8237, an investigational allergy immunotherapy tablet for house dust mite allergy. Merck expects to submit applications for regulatory approval in the United States for each of these candidates, as well as MK-1293 described above, in 2016.
As a result of continued portfolio prioritization, the company is out-licensing or discontinuing selected late-stage clinical development assets. During 2015, the company out-licensed MK1602 and MK-8031, investigational small molecule oral calcitonin gene-related peptide (CGRP) receptor antagonists, which are being developed for the treatment and prevention of migraine.
KEYTRUDA LEADS THE WAY
In terms of product approvals, Merck received several in 2015 that include expanded indications for Keytruda, which was initially approved by the FDA in September 2014 for the treatment of advanced melanoma in patients with disease progression after other therapies. Merck announced during the year that the lung cancer treatment is launching in more than 40 markets, including in the EU.
In 2015, Merck achieved multiple additional regulatory milestones for Keytruda including accelerated approval from the FDA for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 as determined by an FDA-approved test, and who have disease progression on or after platinum-containing chemotherapy. In addition, the FDA approved an expanded indication for Keytruda to include the first-line treatment of patients with unresectable or metastatic melanoma.
Additionally, in 2015, the European Commission approved Keytruda for the treatment of advanced (unresectable or metastatic) melanoma in adults. The Keytruda clinical trials program currently includes more than 30 tumor types in more than 200 clinical trials, including over 100 trials that combine Keytruda with other cancer treatments.
The company is also launching Zepatier and Bridion in the United States, as well as U.S. FDA approval for Bridion (sugammadex) Injection, a medication for the reversal of two types of neuromuscular blocking agents used during surgery.
GROWTH IN HOSPITAL ACUTE CARE MARKET
Merck's strategically focused initiative looks to meet unmet needs in the hospital setting
When Merck announced that it was buying Cubist Pharmaceuticals for $9.5 billion, it signaled that the acute care market within the larger hospital setting was becoming a top priority for the pharma giant. Hospitals are a central hub for healthcare delivery around the world and currently represent 25 percent of overall healthcare spend. At the time of the deal Merck said it was an optimal time to significantly grow its hospital acute care presence because of the positive regulatory and reimbursement trends in the hospital setting and the increasingly important role that hospitals are expected to provide in healthcare overall.
For more than 20 years, Cubist has been a global leader in antibiotics and has built a strong portfolio of both marketed and late-stage pipeline medicines to treat serious and potentially life-threatening infections caused by a broad range of increasingly drug-resistant bacteria. Cubist's antibiotic Cubicin is the only approved once-a-day therapy for both S. aureus bacteremia and complicated skin and skin structure infections (cSSSI). It has been used to treat more than two million patients and continues to be an important therapy in the acute care environment. Cubist's in-line and late-stage pipeline of anti-infective medicines, including Zerbaxa, which is pending approval from the U.S. FDA, will enhance Merck's hospital acute care business in a variety of therapeutic areas, including Gram-positive and Gram-negative multi-drug resistant infections.
Merck said Cubist complements its strategy and the global initiative it launched last year, particularly in the area of its commercial focus on key therapeutic areas that have the potential to deliver the greatest return on investment. With the company's investment in anti-infectives as well as its customer-focused operating model, Merck identified the hospital acute care segment as one of the company's key priority areas to address significant unmet medical needs.
05 ROCHE Headquarters: Basel, Switzerland twitter.com/Roche www.roche.com HEADCOUNT: 91,747 YEAR ESTABLISHED: 1896 TOTAL REVENUES: $48,578 (+1%) PHARMA REVENUES: $37,667 (+2%) NET INCOME: $9,137 (-5%) R&D: $9,667 (-7%) DRUGS APPROVED DRUG INDICATION Avastin (bevacizumab) advanced, metastatic or recurrent non with Tarceva squamous non-small cell lung cancer Gazyva follicular lymphoma (obinutuzumab) Cotellic with Zelboraf advanced melanoma DRUGS PENDING DRUG INDICATION rituximab chronic lymphocytic leukemia subcutaneous formulation bevacizumab 1st line glioblastoma multiforme atezolizumab metastatic non-small cell lung cancer, 2nd-3rd-line, 2nd-line metastatic urothelial bladder cancer PHASE IIB AND BEYOND DRUG INDICATION RG1273 pertuzumab 2nd line HER2-positive breast cancer, gastric cancer RG3502 trastuzumab- early HER2-positive breast cancer adj DM1 RG435 bevacizumab relapsed ovarian cancer, platinum-sensitive RG7159 obinutuzumab diffuse large B-cell lymphoma RG7204 vemurafenib adjuvant melanoma, BRAF mutation positive RG7388 idasanutlin acute myeloid leukemia RG7446 atezolizumab 2nd line non-small cell lung cancer, non-squamous non-small cell lung cancer RG7446+Avastin renal cell cancer atezolizumab RG1569 tocilizumab giant cell arteritis, systemic sclerosis RG3637 lebrikizumab severe asthma RG7413 etrolizumab Crohn's disease RG1450 gantenerumab Alzheimer's disease RG1594 ocrelizumab relapsing multiple sclerosis RG6013 emicizumab hemophilia A EARLY RESEARCH PROJECTS DRUG INDICATION RG7935 Parkinson's disease RG7916 spinal muscular atrophy RG7906 psychiatric disorders RG7893 pain RG7203 schizophrenia RG7992 metabolic diseases RG7944 hepatitis B RG7861 infectious diseases RG6080 bacterial infections RG6024 influenza B RG4929 glaucoma or ocular hypertension RG7880 inflammatory diseases RG7845 autoimmune diseases RG6149 asthma RG6125 rheumatoid arthritis RG6069 fibrosis RG7986 B cell non-Hodgkin's lymphoma RG7888 solid tumors RG7882 ovarian cancer, pancreatic cancer RG7828 hematologic tumors RG7775 acute myeloid leukemia RG6047 metastatic estrogen receptor-positive, HER2-negative breast cancer DRUGS COMING OFF PATENT DRUG INDICATION YEAR Kytril post operative 2016 nausea and vomiting Tamiflu influenza 2017 TOP SELLING DRUGS 2015 DRUG INDICATION SALES MabThera/ rheumatoid arthritis $7,108 2% Rituxan Avastin breast cancer $6,744 4% Herceptin cancer $6,597 4% Lucentis macular degeneraton $1,534 -11% Perjeta breast cancer $1,458 57% Actemra/ rheumatoid arthritis $1,445 17% RoActemra Xolair asthma $1,288 31% Tarceva lung cancer $1,192 -9% Activase/TNKase acute myocardial infarction $943 25% CellCept organ rejection $792 -3%
In Roche's pharmaceuticals division sales rose 5% to $37.6 billion driven by the oncology portfolio (+8%), led by the HER2 medicines and Avastin. Sales of the immunology franchise grew by 24%, driven by the strong uptake of Esbriet, a new medicine for idiopathic pulmonary fibrosis, as well as higher sales of Actemra/RoActemra and Xolair. Sales of Pegasys declined due to competition from a new generation of treatments, while Valcyte/Cymevene and Xeloda faced generic competition as expected.
All regions contributed to the sales growth, with particularly strong performance in the U.S. (+6%) and in Europe (+4%), which was driven by strong demand for the HER2 medicines along with the strong uptake of Esbriet. Growth in the International region (+5%) was driven by key markets including Brazil (+10%) and China (+4%). In Japan, sales grew by 6%, driven by Avastin, the HER2 franchise and the new lung cancer medicine Alecensa.
Roche made positive pipeline progress in 2015. For its investigational medicine ocrelizumab, Roche announced strong data in both relapsing and primary progressive forms of multiple sclerosis. In addition, the company presented promising results for its lead investigational cancer immunotherapy medicine atezolizumab in bladder and lung cancer. Roche also received EU and U.S. approval for Cotellic plus Zelboraf to treat metastatic melanoma, and U.S. approval for the cancer medicine Alecensa for a specific form of lung cancer.
Towards the end of 2015 Roche announced plans to restructure its small molecule manufacturing network, prompting it to close four sites, affecting 1,200 positions. The affected sites are in Clarecastle, Ireland; Leganes, Spain; Segrate, Italy; and Florence, U.S. The company said the closures were necessary to address current underutilization as a result of its evolving portfolio and to support the manufacture of a new generation of specialized small molecule medicines--produced in lower volumes than traditional medicines. For this effort Roche is investing 300 million Swiss francs in a dedicated facility in Kaiseraugst, Switzerland to provide future technology requirements. The transition began in 2016 and is planned to end by 2021. Restructuring costs are estimated to be CHF 1.6 billion until 2021, of which as much as CHF 600 million will be in cash.
BOLSTERING ITS PORTFOLIO
Early in 2015 Roche expanded its portfolio in neuromuscular disease when it acquired Trophos, a privately held biotechnology company based in Marseille, France. Trophos's proprietary screening platform generated olesoxime (TR019622), which is being developed for SMA, a rare and debilitating genetic neuromuscular disease that is most commonly diagnosed in children. Results from a pivotal Phase II clinical trial with olesoxime in SMA showed a beneficial effect on the maintenance of neuromuscular function in individuals with Type II and non-ambulatory Type III SMA, as well as a reduction in medical complications associated with the disease. U.S. and EU regulatory authorities have granted orphan drug designation to olesoxime. The acquisition highlights Roche's commitment to developing medicines for spinal muscular atrophy, a serious disease with no effective treatment.
Roche acquired Kapa Biosystems to strengthen its next-generation sequencing product offerings. Kapa is a provider of genomic tools in the life sciences sector that employs proprietary technologies to optimize enzymes for next-generation sequencing (NGS), as well as polymerase chain reaction (PCR) and realtime PCR applications. The company's proprietary protein engineering technology is highly customizable and allows for the generation and screening of large numbers of enzyme variants. Tailored enzymes with improved performance for specific applications can be rapidly selected, expediting product development timelines. Kapa's portfolio of NGS reagents includes enzymes such as novel DNA polymerases, with the potential to improve the performance of the entire sequencing workflow.
KEY APPROVALS AND BREAKTHROUGHS
In 2015, the FDA and the European Commission approved Cotellic in combination with Zelboraf for the treatment of people with BRAF mutation-positive metastatic melanoma. Updated pivotal data showed that the combination helped people to live significantly longer, with a median of two years, compared to Zelboraf alone.
The FDA also approved Alecensa for people with advanced ALK-positive NSCLC whose disease had progressed following treatment with crizotinib. This is the second approval for this medicine, which was created by Chugai, a member of the Roche Group, and approved in Japan in 2014.
Roche was granted FDA breakthrough therapy designation to ACE910 (RG6013, R05534262) for the prophylactic treatment of people who are 12 years or older with haemophilia A with factor VIII inhibitors. In a Phase I study, ACE910 showed promising results as a prophylactic treatment administered as a weekly subcutaneous injection in people with severe haemophilia A with and without inhibitors to factor VIII.
Roche also received breakthrough status for Actemra/Actemra in systemic sclerosis. According to the company, Actemra/Actemra monotherapy and combination treatment regimens almost double sustained remission rates in people with early rheumatoid arthritis. In addition, five-year sustained efficacy of Actemra/Actemra was demonstrated in children with systemic juvenile idiopathic arthritis. Roche has initiated a global Phase III clinical trial initiated in systemic sclerosis, a potentially fatal disease with limited treatment options.
FDA also granted breakthrough therapy designation for Roche's investigational cancer immunotherapy MPDL3280A (anti-PDL1) in non-small cell lung cancer. The designation was granted for the treatment of people with PD-L1-positive (Programmed Death-Ligand 1) non-small cell lung cancer (NSCLC) whose disease has progressed during or after platinum-based chemotherapy (and appropriate targeted therapy for those with an EGFR mutation-positive or ALK-positive tumor). This is the second FDA Breakthrough Therapy Designation for MPDL3280A following bladder cancer in 2014.
CLINICAL TRIAL ALLIANCES
During the year, Roche and Celldex Therapeutics entered into a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of varlilumab, Celldex's CD27 targeting investigational antibody, and MPDL3280A (anti-PDL1), Roche's investigational cancer immunotherapy in a Phase 1/2 study in renal cell carcinoma.
Varlilumab and MPDL3280A are part of a new class of investigational medicines known as cancer immunotherapies that are designed to harness the body's own immune system to fight cancer through separate yet complementary mechanisms of action that may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells. Preclinical data suggest the combination of these two mechanisms are synergistic and may enhance anti-tumor immune response compared to either agent alone.
In an immunotherapy alliance, Roche teamed up with Amgen to evaluate investigational candidates in cancer patients. The Phase lb study the two firms are collaborating on is to evaluate the safety and efficacy of talimogene laherparepvec, Amgen's investigational oncolytic immunotherapy, in combination with Roche's investigational anti-PDL1 therapy, atezolizumab (also known as MPDL3280A), in patients with triple-negative breast cancer and colorectal cancer with liver metastases.
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells. Atezolizumab is an investigational monoclonal antibody designed to interfere with the PD-L1 protein.
The combination trial aims to activate an anti-tumor immune response with talimogene laherparepvec and to block inhibitory T cell checkpoints with atezolizumab, to potentially increase the anti-tumor activity relative to each agent alone.
Roche and Upsher-Smith Laboratories, through its wholly-owned UK subsidiary Proximagen, formed an agreement for the further development of a novel, oral small molecule inhibitor of Vascular Adhesion Protein 1 (VAP-1), a cell-adhesion molecule that may be effective in the treatment of inflammatory diseases. The VAP-1 inhibitor is currently in Phase II clinical development. Roche is granted a worldwide exclusive license to develop and commercialize the compound. In a novel collaboration model, Roche and Proximagen will conduct additional Phase II studies to further define the therapeutic potential of the VAP-1 inhibitor. Based on these data Roche will assume responsibility for late stage development and worldwide commercialization. Proximagen will receive an upfront payment, along with downstream development, regulatory and sales milestones. In addition, Proximagen will also receive tiered royalties on net sales of a potential future product containing the molecule.
On the research front, Roche entered a collaboration with Catalent, through its subsidiary Redwood Biosdence, to develop next-generation molecules coupling different therapeutic modalities using Catalent's proprietary SmartTag technology. Roche gains non-exclusive access to the SmarTag platform and will have an option to take commercial licenses to develop molecules directed to a defined number of targets. Use of SmarTag Catalent's programmable protein-modification technology, combined with the highly stable hydrazino-Pictet-Spengler (HIPS) conjugation platform, will permit evaluation of alternative sites of drug conjugation so that Roche may develop molecules optimized for efficacy, safety and stability. Roche paid Catalent an upfront fee of $1 million and is to provide additional research funding during the initial phase of the collaboration. Catalent has the potential to receive up to $618 million in development and commercial milestones, plus royalties on net sales of products, if Roche pursues commercial licenses and all options are exercised.
In another alliance, Roche, Meiji Seika Pharma and Fedora formed a license agreement for the development and commercialization of OP0595, a beta-lactamase inhibitor in Phase I clinical development. Under the agreement, Roche obtains worldwide rights from both companies for development and commercialization with the exception of Japan, where Meiji will retain sole commercialization rights. Beta-lactamase inhibitors restore or potentiate the activity of beta-lactam antibiotics. The combination of OP0595 with a beta-lactam antibiotic targets severe infections caused by Enterobacteriaceae, including multi-drug-resistant strains. Roche entered the deal because it said there is an urgent need for new antibiotics able to combat the increasing resistance to antibiotics that is being seen worldwide.
ROCHE TEAMS UP WITH FOUNDATION MEDICINE
Collaboration focuses on molecular information in oncology
In January 2015 Roche and Foundation Medicine, Inc. (FMI) entered a broad strategic collaboration to further advance FMI's market-leading position in molecular information and genomic analysis while providing Roche the opportunity to optimize the identification and development of novel treatment options for cancer patients.
According to the companies, the emerging field of molecular information and genomic analysis will play an increasingly important role for future medicines and diagnostic solutions, in particular for cancer patients. FMI supports physicians by providing comprehensive molecular information to characterize a tumor that is being matched with approved targeted therapy options and novel treatments under development. Understanding the comprehensive genomic profile of a cancer patient's disease will enable better personalized healthcare solutions to optimize treatment outcomes for patients.
Under the terms of the R&D collaboration agreement, Roche is committing to R&D funding of potentially more than $150 million for a minimum of five years and will contribute its expertise and breadth in oncology. FMI will continue to operate independently and will contribute its experience in the development of comprehensive genomic profiling tests for oncology. The initial focus of the R&D collaboration will be on developing genomic profile tests for cancer immunotherapies and for continuous blood-based monitoring.
Roche will be able to utilize FMI's proprietary molecular information platform to standardize clinical trial testing. This aspect of the relationship is designed to enable comparability of clinical trial results for R&D purposes, and ultimately in the clinic.
06 GLAXOSMITHKLINE Headquarters: Brentford, Middlesex, UK twitter.com/GSK www.gsk.com HEADCOUNT: 101,255 YEAR ESTABLISHED: 2000 REVENUES: $35,463 (-7%) NET INCOME: $12,410 (+166%) R&D: $5,277 (-7%) DRUGS APPROVED DRUG INDICATION Nucala severe asthma Volibris pulmonary arterial hypertension Breo Ellipta once-daily treatment of asthma DRUGS PENDING DRUG INDICATION 2696273 adenosine deaminase severe combined immune deficiency chlorhexidine prevention of omphalitis FluLaval Quadrivalent influenza A subtype and type B viruses PHASE IIB AND BEYOND DRUG INDICATION 3684934 HIV tafenoquine plasmodium vivax malaria mepolizumab COPD sirukumab rheumatoid arthritis, giant cell arteritis systemic lupus vasculitis erythematosus 2998728 transthyretin-mediated amyloidosis mepolizumab eosinophilic granulomatosis with polyangiitis Shingrix herpes zoster prophylaxis MMR measles, mumps, rubella prophylaxis retosiban spontaneous pre-term labour EARLY RESEARCH PROJECTS DRUG INDICATION mepolizumab severe atopic dermatitis oxytocin postpartum hemorrhage 2881078 muscle wasting 2798745 heart failure daprodustat wound healing RSV vaccine respiratory syncytial virus prophylaxis HIV vaccine HIV infection prophylaxis 2696277 beta-thalassemia 3179106 inflammatory disorders of the bowel 3117391 rheumatoid arthritis 3050002 psoriatic arthritis 2831781 autoimmune disease 2618960 Sjogren's syndrome 2330811 systemic sclerosis 525762 solid tumors and haematological malignancies 2256098 mesothelioma 2636771 castration resistant prostate cancer 2857916 multiple myeloma 2879552 acute myeloid leukemia and small cell lung cancer 3008348 idiopathic pulmonary fibrosis 2878175 hepatitis C 3389404 hepatitis B DRUGS COMING OFF PATENT DRUG INDICATION YEAR Zofran nausea and vomiting 2016 Valtrex herpes viruses 2016 Serevent asthma 2016 Tykerb breast cancer 2017 Kivexa HIV 2019 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Seretide/Advair asthma, COPD $5,632 -19% Infanrix, Pediarix pediatric vaccine $1,121 -18% Epzicom/Kivexa HIV $1,068 -16% Avodart enlarged prostate $1,006 -24% Flixotide/Flovent respiratory $953 -18% Ventolin asthma $949 -13% Lamictal anti-epileptic $812 -7% Augmentin antibacterial $808 -14%
In 2015 GlaxoSmithKline (GSK) reported sales of $35.5 billion. The key event was the completion of its three-part deal with Novartis that was announced the year before. As a result of this transaction, GSK acquired Novartis's global vaccines business, excluding influenza vaccines, for $5.25 billion. As part of the deal, GSK has also created a new leading consumer healthcare joint venture with Novartis in which GSK has majority control of 63.5%. Finally, GSK divested its oncology business to Novartis for $16 billion.
Following the Novartis deal, GSK further expanded its vaccines presence in the U.S. by establishing a new global center for vaccines research and development (R&D) in Rockville, MD. The site will become one of three global vaccines R&D centers for GSK, complementing the company's existing global R&D centers in Rixensart, Belgium and in Siena, Italy, a site GSK recently acquired as part of the Novartis deal.
The new U.S. vaccines R&D center will expand GSK's efforts to discover and develop novel vaccines and it will consolidate vaccines R&D activities currently conducted at other GSK sites including in Philadelphia, PA and Cambridge, MA, into one centralized location. Key late stage development programs, as well as vaccine discovery and new platform technology development will be led from Rockville.
Also on the research front, GSK unveiled plans to become a key partner, with an investment of $25 million, in a pioneering new global fund for dementia research. The Dementia Discovery Fund, established by the UK government with initial commitments totaling $100 million, brings together leading pharmaceutical companies, the UK government and Alzheimer's Research UK to address the rising threat posed by dementia by supporting research into future treatments. The fund aims to identify and nurture promising new avenues of research from around the world in the field of dementia and supports GSK's commitment to explore novel, collaborative approaches in challenging areas of research.
In a unique public-private collaboration formed to create an HIV Cure center and a new company to bring together academic and pharmaceutical research scientists, The University of North Carolina at Chapel Hill and GSK, unveiled plans to create a dedicated HIV Cure center and a jointly owned new company that will focus on discovering a cure for HIV/AIDS. The HIV Cure center will be located on the UNC-Chapel Hill campus and will focus exclusively on finding a cure for HIV/AIDS. The new company, Qura Therapeutics, will handle the business side of the partnership, including intellectual property, commercialization, manufacturing and governance. Together, the HIV Cure center and Qura Therapeutics will serve as a catalyst for additional partners and public funding.
Through the new company, GSK will invest $4 million per year for five years to fund the initial HIV Cure center research plan, and a small research team from GSK will move to Chapel Hill to be co-located with UNC researchers. The University will provide world-class laboratory space on its medical campus for the HIV Cure center and the new company.
Further strengthening its HIV pipeline and outlook, GSK, through its global HIV business, ViiV Healthcare, reached two separate agreements with Bristol-Myers Squibb (BMS), to acquire its late-stage HIV R&D assets and to acquire its portfolio of preclinical and discovery stage HIV research assets.
Late stage assets, including fostemsavir (BMS-663068), an attachment inhibitor, currently in Phase III development for heavily treatment experienced patients that has received a breakthrough designation from the FDA and is expected to be filed for regulatory approval in 2018. The second late stage asset is a maturation inhibitor (BMS-955176), currently in Phase lib development for both treatment-naive and treatment experienced patients. A back-up maturation inhibitor candidate (BMS-986173) is also included in the purchase.
Assets in preclinical and discovery phases of development include a novel biologic (BMS-986197) with a triple mechanism of action, a further maturation inhibitor, an allosteric integrase inhibitor and a capsid inhibitor.
Also on the research front, during the year GSK teamed up with Merck to initiate a Phase I clinical trial designed to evaluate GSK's investigational immunotherapy GSK3174998 as monotherapy and in combination with Merck's anti-PD-1 therapy, Keytruda (pembrolizumab) in patients with locally advanced, recurrent or metastatic solid tumor(s) that have progressed after standard treatment.
In terms of acquisitions, in February GSK acquired GlycoVaxyn AG, a specialist vaccine biopharmaceutical company based in Switzerland. Since forming a scientific collaboration in 2012, GSK has held a minority stake in GlycoVaxyn. It acquired the remaining shares for $190 million to take full ownership of the company.
GlycoVaxyn has developed an innovative biological conjugation platform technology, which has the potential to play an important role in the development of new prophylactic and therapeutic vaccines for a range of bacterial diseases. This proprietary technology also has the potential to enable GSK to develop a simplified conjugate vaccine manufacturing process.
As part of the deal, GSK also acquired a small number of early stage vaccines in development against bacterial infections such as pneumonia, pseudomonas, staphylococcus aureus and Shigellosis, supplementing the company's existing vaccines pipeline.
Also of note in 2015, GSK started building its largest Indian tablet manufacturing pharmaceutical factory. When fully operational in 2017, the $140 million factory will make more than 8 billion tablets and 1 billion capsules a year in the areas of gastroenterology and anti-inflammatory medicines for the Indian market. The facility will be built on a 50-acre site in Vemgal, Karnataka. The facility will also include a warehouse, site infrastructure, employee welfare center and utilities to support the manufacturing and packing of the medicines.
During the year GSK also established a new global headquarters for Asia in Singapore. The eight-story, nearly 15,000 square meter facility will have capacity for up to 1,000 employees across GSK's pharmaceuticals, vaccines and consumer healthcare businesses. Key leadership is already transitioning into the region with almost 150 global or regional roles moving to Singapore in the last year. Construction is expected to be complete by the end of 2016 and all employees will be situated at the new site during the second half of 2017.
07 GILEAD SCIENCES Headquarters: Foster City, CA twitter.com/gileadsciences www.gilead.com HEADCOUNT: 8,000 YEAR ESTABLISHED: 1987 REVENUES: $32,639 (+31%) NET INCOME: $18,108 (+50%) R&D: $3,014 (+6%) DRUGS APPROVED DRUG INDICATION Descovy HIV Odefsey HIV-1 infection Harvoni in chronic hepatitis C with advanced liver combination with disease, once-daily STR ribavirin Genvoya STR HIV-1 infection Letairis pulmonary arterial hypertension DRUGS PENDING DRUG INDICATION STR rilpivirine/ HIV/AIDS emtricitabine/tenofovir alafenamide STR of sofosbuvir/ chronic HCV infection velpatasvir Tenofovir alafenamide chronic HBV infection CTAF) PHASE IIB AND BEYOND DRUG INDICATION Bictegravir/F/TAF HIV/AIDS Sofosbuvir, velpatasvir chronic HCV infection and voxiiaprevir Idelalisib relapsed refractory CLL Momelotinib myelofibrosis GS-5745 gastric cancer Eleclazine long CT-3 syndrome GS-5745 ulcerative colitis EARLY RESEARCH PROJECTS DRUG INDICATION GS-9620 HIV/AIDS GS-9674 NASH GS-5745 colid tumors GS-4059 B-cell malignancies GS-5829 solid tumors GS-5745 COPD, rheumatoid arthritis GS-9876 rheumatoid arthritis GS-5734 Ebola virus infection DRUGS COMING OFF PATENT DRUG INDICATION YEAR Emtriva HIV 2016 Atripla HIV 2016 Truvada HIV 2017 Complera HIV 2017-2018 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Harvoni chronic hepatitis C $13,864 552% Sovaldi chronic hepatitis C $5,276 -49% Truvada HIV $3,459 4% Atripla HIV $3,134 -10% Complera/ HIV $1,427 16% Eviplera Stribild HIV $1,825 52% Viread chronic hepatitis B $1,108 5%
Having been referred to as "the Apple of healthcare" another jump for Gilead in the 2015 rankings has the burgeoning biotech up two spots to number 7. While the company's growth is impressive, driven by staggering Harvoni and Sovaldi sales of $13.9 billion and $5.3 billion, respectively, maintaining this surge within a more crowded Hep C market may prove difficult. Despite pricing pressures and competition for its top Hep C sellers, it still holds a solid 90% market share. Gilead also maintains its dominant position with its growing flagship HIV franchise.
The first quarter of 2016 saw revenues up 3% to $7.8 billion, while net income was down 16% to $3.6 billion due to acquisition-related, up-front collaboration, stock-based compensation expenses, as well as reflecting lower revenues in the Hep C arena. Antiviral product sales, which include HIV and liver disease areas, were $7.2 billion, up 3%. Truvada sales were up 16% to $898 million, Atripla sales declined 8% to $675 million due to patent expirations, and Stribild sales were up 34% to $477 million. While Harvoni sales slipped 16% in the first quarter, Sovaldi sales were up 31%.
The Hep C market saw a significant drop in prices as a result of the launch of Merck's Zepatier in January, which considerably undercut both AbbVie's Viekira Pak and Gilead's Harvoni on price--not to mention this strategy could give payers the leverage needed to negotiate even further discounts. Viekira Pak launched in December 2014, just two months after Harvoni was approved, and exclusive deals with insurers to cover the drug in return for discounts quickly ensued. Gilead was forced to do the same, impacting 1Q16 sales.
Compared to its closest competitors, AbbVie, Merck, and Celgene, Gilead's financials and assets appear in good working order, and its pipeline comprises several late-stage product candidates for high value indications, namely cancer, heart disease, and HIV. While these candidates are not likely to have the financial impact of Harvoni and Sovaldi, they're diversified and have the potential to replace some of the lost revenue in the Hep C arena, which, due to the curative nature of these therapies, is not likely to be able to support multiple blockbusters long term.
Additions to Gilead's HIV therapies include the FDA approval of Odefsey (emtricitabine /rilpivirine /tenofovir alafenamide or R/F/TAF) for the treatment of HIV-1 infection. Odefsey is Gilead's second TAF-based regimen to win FDA approval and represents the smallest pill of any single-tablet regimen currently available for the treatment of HIV. The drug will likely gain EU approval as well, with the European CHMP adopting a Positive Opinion for Odefsey this past April. Emtricitabine and tenofovir alafenamide are from Gilead, while rilpivirine is from Janssen Sciences Ireland.
The European Medicines Agency (EMA) also adopted a positive opinion for two doses of Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg, F/TAF), an investigational fixed-dose combination for the treatment of HIV-1 in combination with other antiretroviral agents.
Antiviral asset bictegravir (GS-9883), an investigational integrase strand transfer inhibitor achieved proof-of-concept based on data from four preclinical and Phase I studies evaluating the antiviral potency, resistance profile, pharmacokinetics and safety. Bictegravir, including in combination with tenofovir alafenamide and emtricitabine as a single tablet regimen, is an investigational treatment for HIV currently in Phase III trials as part of the single tablet regimen.
In HCV, Harvoni picked up two supplemental indications for use in chronic hepatitis C patients with advanced liver disease. Also, the FDA granted priority review to the company's NDA for an investigational once-daily fixed-dose combination of sofosbuvir and velpatasvir (SOF/VEL) for the treatment of chronic genotype 1-6 HCV infection. The FDA has set a target action date under the Prescription Drug User Fee Act of June 28, 2016.
Finally, while Gilead terminated its Phase II study of the investigational monoclonal antibody simtuzumab in patients with idiopathic pulmonary fibrosis (IPF) due to lack of efficacy, Phase II studies of simtuzumab are ongoing in patients with non-alcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC).
In addition to these pipeline assets, several noteworthy acquisitions and collaborations broadened Gilead's portfolio. Most recently, the company acquired Nimbus Apollo and its AcetylCoA Carboxylase (ACC) inhibitor program for $400 million upfront, and an additional $800 million in development milestones. The Nimbus Apollo program includes the lead candidate NDI-010976, an ACC inhibitor, and other preclinical ACC inhibitors for the treatment of NASH, and for the potential treatment of hepatocellular carcinoma (HCC) and other diseases. NDI-010976 was Fast Tracked by the FDA in February 2016 and Phase I data for the compound is expected to be available soon.
Gilead also acquired EpiTherapeutics, a privately-held Danish company, for $65 million, gaining a portfolio of histone demethylases for the treatment of certain cancers.
Finally, Galapagos and Gilead Sciences completed the closing of their global license and collaboration agreement on filgotinib, triggering an upfront license fee payment of $300 million to Galapagos. Gilead has also made a $425 million equity investment in Galapagos and now owns 14.75% of its outstanding shares.
The companies entered a collaboration for the joint development and commercialization of filgotinib in inflammatory diseases in December 2015. Galapagos co-funds 20% of global development activities and Gilead is responsible for manufacturing and worldwide marketing and sales activities.
A Phase III program with filgotinib in rheumatoid arthritis will be initiated mid-2016. Filgotinib has also been shown to be safe and effective in moderate to severe Crohn's disease, based on Phase II study results.
In executive news, as of March 2016, John C. Martin, Ph.D., chairman and chief executive officer of Gilead stepped down, assuming the role of executive chairman of the company. John F. Milligan, Ph.D., was promoted to CEO and will serve on the board of directors. Dr. Martin joined the company in 1990 and served as CEO since 1996. Dr. Milligan also joined Gilead in 1990 and most recently served as president and chief operating officer. Under Martin, Gilead grew from a small biotech worth $1 billion, to a top 10 biopharma company bringing in nearly $33 billion in 2015. If Dr. Milligan can keep pace in today's challenging environment, Gilead's outlook is strong.
08 JOHNSON & JOHNSON Headquarters: New Brunswick, NJ twitter.com/JNJComm www.jnj.com HEADCOUNT: 127,000 YEAR ESTABLISHED: 1887 REVENUES: $70,074 (-6%) PHARMA REVENUES: $31,430 (-3%) NET INCOME: $16,323 (+18%) R&D: $9,046 (+7%) DRUGS APPROVED DRUG INDICATION Darzalex double refractory multiple myeloma Edurant STR single tablet regimen for HIV Invega Trinza schizophrenia--3 month injectable Imbruvica Waldenstrom's macroglobulinemia Prezcobix HIV-1 Yondelis unresectable or metastatic liposarcoma or leiomyosarcoma DRUGS PENDING DRUG INDICATION Invokana fixed dose combination with Metformin XR, IR Stelara Crohn's disease Imbruvica relapsed-refractory chronic lymphocytic leukemia with Bendamustine and Rituximab PHASE IIB AND BEYOND DRUG INDICATION Xarelto (rivaroxaban) major adverse cardiac events, prevention of symptomatic VTE Invokana (canagliflozin) diabetic nephropathy guselkurnab moderate to severe plaque psoriasis Simponi Aria ankylosing spondylitis (golimumab) esketamine treatment-restistant depression Imbruvica mantle cell lymphoma, indolant non-Hodgkins lymphoma apalutamide prostate cancer (ARN-509) JNJ927/ARN-509/ prostate cancer Zytiga Yondelis (trabectedin) relapsed ovarian cancer EARLY RESEARCH PROJECTS DRUG INDICATION CPI-1205 B-cell lymphoma CPI-0610 leukemia, myelocytic, acute; myelodys-plastic syndrome Galantamine obesity Doxazosin PTSD; alcohol use disorder VLX600 refractory cancer FLX925 acute myeloid leukemia ALRN-6924 solid tumor; lymphoma LY3002813 Alzheimer disease CRLX301 advanced solid tumor malignancy CMB305 sarcoma; melanoma; non- small cell lung cancer; ovarian cancer MGCD516 advanced cancer AGT-182 mucopolysaccharidosis DRUGS COMING OFF PATENT DRUG INDICATION YEAR Zytiga metastatic, castrate 2016 resistant prostate cancer Topamax migraine 2016 Concerta ADHD 2017 Prezista HIV/AIDS 2017 Risperdal Consta schizophrenia 2017 Invega Sustenna schizophrenia 2017 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Remicade rheumatoid arthritis $6,561 -5% Stelara psoriasis $2,474 19% Olysio/Sovriad hepatitis C $2,302 n/a Zytiga prostate cancer $2,231 0% Xarelto deep vein thrombosis, pulmonary embolism $1,868 23% Invega Sustenna schizophrenia $1,830 15% Prezista HIV/AIDS $1,810 -1% Velcade velcade, mantle cell lymphoma $1,333 -18% Simponi rheumatoid arthritis $1,328 12% Invokana type 2 diabetes $1,308 n/a
Johnson & Johnson (J&J) has a portfolio focused on five core therapeutic areas--immunology, infectious diseases and vaccines, neuroscience, cardiovascular and metabolism, and oncology. Combined segment sales in 2015 were $31.4 billion, a decrease of 2.7% from 2014. J&J said the pharma segment was negatively impacted by the introduction of competitive products to the company's Hepatitis C products, Olysio/Sovriad (simeprevir) and Incivo (telaprevir).
Immunology products achieved sales of $10.4 billion in 2015, representing an increase of 2.1% compared to the prior year driven by the increased sales of Sterlara (ustekinumab) and Simponi/Simponi Aria (golimumab). Growth was partially offset by lower Remicade (infliximab) sales due to the weakening of the euro and biosimilar competition in Europe.
Infectious disease products sales were $3.7 billion, a decline of 34.7% from 2014. Competitive products to the company's Hepatitis C products, Olysio/Sovriad and Incivo had a significant negative impact on U.S. sales and will continue to have a negative impact on future sales, according to the company.
Neuroscience products sales were $6.3 billion, a decrease of 3.5% from 2014. J&J reports the U.S. sales growth of Concerta/methylphenidate was primarily due to a therapeutic equivalence reclassification of generic competitors by the FDA in November 2014. In addition, strong sales were reported upon the launch of Invega Trinza. However, neuroscience products sales were negatively impacted by the U.S. divestiture of Nucynta (tapentadol) and lower sales of Risperdal Consta (risperidone).
Oncology products achieved sales growth of $4.7 billion in 2015, representing an increase of 5.3% as compared to the prior year. Contributors to the growth were strong sales of Imbruvica (ibrutinib) due to the approval of new indications, additional country launches and strong patient uptake. Additionally, sales of Zytiga (abiraterone acetate) grew in the U.S. and in Asia and Latin America, but were lower in Europe due to competition.
Cardiovascular, metabolism and other products achieved sales of $6.4 billion in 2015, representing an increase of 15% as compared to the prior year due to strong sales of Xarelto (rivaroxaban) and Invokana/Invokamet (canagliflozin).
While overall sales were down, the innovation engine at J&J steams ahead. During the year, the pharma giant unveiled plans to file for regulatory approval of more than 10 new products between 2015 and 2019, each with the potential to exceed $1 billion in revenue, as well as more than 40 line extensions of existing and new medicines. Janssen Pharmaceuticals, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, has launched 14 new products since 2009, seven of which already exceed or are on track to achieve sales in excess of $1 billion.
Late-stage products expected to drive growth in the next several years, following regulatory approvals, include daratumumab for multiple myeloma; sirukumab for rheumatoid arthritis; guselkumab for psoriasis; JNJ-927 (ARN-509) for pre-metastatic prostate cancer; imetelstat for myelofibrosis; JNJ-493 (FGFRi kinase inhibitor) for urothelial cancer; esketamine for treatment-resistant depression; AL-8176 for respiratory syncytial virus (RSV); fulranumab for osteoarthritic pain; JNJ-872 (VX-787) for influenza A; JNJ-922 (Orexin-2 antagonist) for primary insomnia; and AL-335 for hepatitis C.
In addition, daratumumab and esketamine have both received Breakthrough Therapy Designations from the U.S. FDA. Janssen also announced plans to submit a Biologic Licensing Application to the FDA and a Marketing Authorization Application to the EMA this year for daratumumab in double refractory multiple myeloma.
ACQUISITIONS AND PARTNERSHIPS
In March 2015, Janssen acquired XO1 Limited, a privately held asset-centric virtual biopharmaceutical company founded to develop the anti-thrombin antibody ichorcumab. Ichorcumab is a recombinant human antibody developed to mimic the activity of a human antibody, which appears to produce an anti-coagulated state without predisposition to bleeding.
Ichorcumab complements the Janssen cardiovascular portfolio. With its strong position in the fields of anticoagulation and biologies, J&J is well positioned to explore the potential of this next generation anticoagulant. The opportunity was identified and facilitated through Johnson & Johnson Innovation, London.
Ichorcumab was initially developed by Cambridge University Hospitals and Cambridge University with support from Cambridge Enterprise, the University's commercialization arm. The technology was licensed by Cambridge Enterprise to XO1 Limited in order to take its development towards the clinic. XO1 Limited was established by Index Ventures as an asset centric company, a model advanced by Index, via a fund launched in 2012 in which Johnson & Johnson Innovation--JJDC, Inc. is an investor.
In another acquisition deal later in the year, J&J strengthened its pipeline to combat Hepatitis B virus when it acquired Novira Therapeutics, a privately held, clinical-stage biopharmaceutical company. The acquisition included Novira's portfolio of novel antivirals, including its lead candidate, NVR 3-778, a small molecule, direct acting antiviral, for oral administration in patients with HBV that inhibits the HBV core or capsid protein. HBV core is a novel and promising drug target since it is involved in multiple activities required for viral replication and persistence.
During the year J&J also completed the divestiture of its Cordis business to Cardinal Health for an approximate value of $2 billion. The Cordis business is a global leader in the development and manufacture of interventional vascular technology and generated net revenues of approximately $780 million in 2014. At the time of the deal J&J reinforced its commitment to cardiovascular disease, focusing on its leading cardiovascular medicine, Xarelto.
During the year Janssen entered into a collaboration and license agreement with Bavarian Nordic to leverage their MVA-BN technology, jointly with Janssen's own AdVac technology, in the development and commercialization of a heterologous prime-boost vaccine for the treatment of Human Papillomavirus (HPV) chronic infections, which can lead to cancer. Janssen will conduct all clinical development and, subject to regulatory approval, will be responsible for registration, distribution and commercialization of the potential combination vaccine worldwide.
Janssen also obtained worldwide rights, excluding China and Korea, to develop and commercialize oxyntomodulin-based therapies including HM12525A, a biologic that is completed Phase I and entered Phase II, from Hanmi Pharmaceutical. HM12525A is an oxyntomodulin-based therapy (GLP-l/glucagon receptor dual agonist) that has shown evidence of improving multiple metabolic parameters that lead to improved blood glucose, body weight, and insulin sensitivity. J&J said this asset has the potential, as a once weekly therapy, to be a best-in-class oxyntomodulin-based therapy.
09 ASTRAZENECA Headquarters: London, UK twitter.com/astrazeneca www.astrazeneca.com HEADCOUNT: 61,500 YEAR ESTABLISHED: 1999 REVENUES: $24,708 (-5%) NET INCOME: $2,826 (+129%) R&D: $5,997 (+7%) DRUGS APPROVED DRUG INDICATION Bevespi Aerosphere COPD Tagrisso mutation-positive metastatic non-small cell lung cancer Zurampic gout Brilinta patients with a history of heart attack Iressa 1st line EGFR non-small cell lung cancer DRUGS PENDING DRUG INDICATION saxa/dapa (saxagliptin type-2 diabetes and dapagliflozin) Caz AVI serious infections Brilique patients with a history of heart attack DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION Brilinta arterial thrombosis Epanova severe hypertriglyceridaemia Farxiga type 2 diabetes Tagrisso 2nd line advanced EGFRm, NSCLC acalabrutinib B-cell blood cancers cediranib ICON 6 PSR ovarian cancer selumetinib thyroid cancer PT010 COPD Zurampic gout brodalumab psoriasis AZD3293 early Alzheimer's disease MEDI-550 pandemic flu Zinforo pneumonia, skin infections EARLY RESEARCH PROJECTS DRUG INDICATION AZD4076 non-alcoholic fatty liver disease AZD5718 coronary artery disease MEDI8111 trauma/bleeding MEDI0382 diabetes/obesity AZD0156 solid tumors AZD9150 haematological malignancies AZD9496 breast cancer AZD9291 + advanced EGFRm NSCLC Durvalumab AZD1419 asthma AZD5634 cystic fibrosis AZD7896 COPD AZD9567 rheumatoid arthritis MEDI15872 systemic lupus erythematosus MEDI9314 atopic dermatitis MEDI4920 primary Sjogren's syndrome ATM AVI serious bacterial infections AZD8108 suicidal ideation MEDI7352 osteoarthritis pain DRUGS COMING OFF PATENT DRUG INDICATION YEAR Crestor cholesterol 2016 Byetta type 2 diabetes 2016-2020 Rhinocort allergy 2017 Symbicort asthma 2017 Seroquel XR anti-psychotic 2017 Iressa lung cancer 2017 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Crestor cholesterol $5,017 -9% Symbicort asthma $3,394 -11% Nexium acid reflux $2,496 -32% Seroquel XR anti-psychotic $1,025 -16% Pulmicort asthma $1,014 7% Zoladex cancer $816 -12% Onglyza type 2 diabetes $786 -4% Seloken/Toprol-XL hypertention $710 -6% Faslodex breast cancer $704 -2% Synagis RSV $662 -26%
Continuing to support is growing biologies portfolio, AstraZeneca, which reported sales of $24.7 billion in 2015, made several significant transactions during the year to bolster its biologies growth strategy. The company laid out plans to invest approximately $285 million in a new high-tech facility for manufacturing of biological medicines in Sodertalje, Sweden. The new plant will be focused on filling and packaging of protein therapeutics. It is anticipated that the new facility will supply medicines for clinical trial programs of AstraZeneca and MedImmune, the company's global biologies research and development arm, from the end of 2018, and will deliver finished products for commercial use once fully operational by 2019.
Sodertalje is currently home to AstraZeneca's largest global tablets and capsules manufacturing facility and is also a launch platform site for the company, with specialist capabilities onsite that allow large-scale production of new medicines, working closely with the research and development organization.
Biotech medicines make up 50% of the company's pipeline with more than 120 ongoing programs, including more than 30 in clinical development. The new manufacturing facility in Sweden will support the progression of drug candidates across the main therapy areas and be aligned with investments being made in the current biologies manufacturing centers, such as the expansion in Frederick, MD, announced in November 2014.
Expanding its biologies footprint further, AstraZeneca purchased a high-tech biologies bulk manufacturing facility from Amgen, growing its biologies manufacturing capability in the U.S. The Lake Center facility, located in Boulder, CO, is expected to be operational and licensed for commercial production by late 2017. Down the road, the company said this site will eventually double the biologies manufacturing capacity in the U.S. to accommodate its maturing pipeline.
Further supporting its push into biologies, AstraZeneca, through MedImmune, entered into a license agreement and collaboration with Inovio Pharmaceuticals, a biotechnology company developing DNA-based immunotherapies for cancer and infectious diseases. MedImmune acquired exclusive rights to Inovio's INO-3112 immunotherapy, which targets cancers caused by human papillomavirus (HPV) types 16 and 18. INO3112, which is in Phase I/II clinical trials for cervical and head and neck cancers, works by generating killer T-cell responses that are able to destroy HPV 16- and 18-driven tumours. These HPV types are responsible for more than 70 percent of cervical pre-cancers and cancers.
MedImmune made an upfront payment of $27.5 million to Inovio as well as potential future payments upon reaching development and commercial milestones totaling up to $700 million. MedImmune will fund all development costs. Inovio is entitled to receive up to double-digit tiered royalties on INO-3112 product sales. MedImmune intends to study INO3112 in combination with selected immunotherapy molecules within its pipeline in HPV-driven cancers. Emerging evidence suggests that the benefits from immuno-oncology molecules, such as those in MedImmune's portfolio, can be enhanced when they are used in combination with cancer vaccines that generate tumour-specific T-cells.
During the year MedImmune also formed a strategic alliance with WuXi AppTec to bring research and technical capability for biologies to China. AstraZeneca will have the option to acquire WuXi's biologies manufacturing facility in Wuxi city in the next few years. Prior to that, WuXi Biologies remains the exclusive partner for R&D manufacturing for MedImmune's innovative biologies in China. The alliance builds on the existing joint venture between the companies formed in 2012 to develop and commercialize MEDI5117, a biologic for autoimmune and inflammatory diseases. The IND application was subsequently accepted by CFDA for review in March 2015. WuXi will continue manufacturing for the program at its cGMP facilities. WuXi is building its largest biomanufacturing facility using 14 2000L and two 1000L disposable bioreactors to support late-phase clinical and commercial manufacturing. The first phase of the facility will be operational in January 2017.
AstraZeneca also formed a three-year collaboration with Orca Pharmaceuticals, a UK-based biopharmaceutical company, to develop inhibitors of retinoic acid-related orphan nuclear receptor gamma (ROR[gamma]). Inhibitors of this receptor are believed to have potential against a wide range of autoimmune diseases for which there is currently no safe, orally available and effective treatment.
ROR[gamma] plays a key role in the immune system. Specifically, it helps to convert a population of immune cells called CD4+ T cells into T-helper 17 (TH17) cells, which, in turn, produce chemicals (cytokines) that drive the immune response. However, excessive activity of TH17 cells and other ROR[gamma]+ immune cells have been implicated in a wide range of autoimmune conditions such as inflammatory bowel disease, psoriasis, arthritis and multiple sclerosis.
AstraZeneca gains access to ROR[gamma] inhibitors developed by Orca Pharmaceuticals and will integrate these into its in-house program. Working together, scientists from AstraZeneca and Orca Pharmaceuticals will identify lead compounds from this program for progression and characterize the autoimmune condition to which the lead compounds are best suited. Orca Pharmaceuticals received an upfront payment with potential future milestone payments from AstraZeneca dependent on the success of their ROR[gamma] inhibitors in the program with a potential total value of $122.5 million. AstraZeneca has the option to acquire the Orca compounds at the end of the collaboration.
AstraZeneca formed some other collaborations of note in 2015. Together with Pelago Bioscience AB, it entered into a 2-year strategic research collaboration and license agreement. The companies will collaborate on specified joint projects and AstraZeneca will also be granted a license to use and apply the Cellular Thermal Shift Assay (CETSA) for determination and quantification of drug-target interactions in other AstraZeneca discovery projects.
Peregrine Pharmaceuticals expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, late-stage trial. The companies will now evaluate the combination of Peregrine's phosphatidylserine (PS)-targeted immune-activator, bavituximab, and AstraZeneca's anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), in a global Phase II study in previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). Peregrine will conduct the randomized Phase II trial.
Valeant Pharmaceuticals' affiliate entered into a collaboration agreement with AstraZeneca under which Valeant was granted an exclusive license to develop and commercialize brodalumab, an IL-17 receptor monoclonal antibody in development for moderate-to-severe plaque psoriasis and psoriatic arthritis.
Lastly, Charles River Laboratories and AstraZeneca extended their initial three-year partnership for an additional five-year period through 2020. Charles River retains its position as AstraZenca's preferred strategic partner for outsourced regulated safety assessment and development DMPK (drug metabolism and pharmacokinetics).
10 ABBVIE Headquarters: North Chicago, IL twitter.com/abbvie www.abbvie.com HEADCOUNT: 28,000 YEAR ESTABLISHED: 2013 REVENUES: $22,859 (+15%) NET INCOME: $5,144 (+190%) R&D: $4,285 (+30%) DRUGS APPROVED DRUG INDICATION Imbruvica chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia Zinbryta multiple sclerosis once monthly Viekira Pak chronic hepatitis C virus Venclexta chronic lymphocytic leukemia Viekirax genotype 1 chronic hepatitis C Humira moderate to severe hidradenitis suppurativa Technivie genotype 4 chronic hepatitis C DRUGS PENDING DRUG INDICATION Humira non-infectious uveitis, pediatric Crohn's disease PHASE IIB AND BEYOND DRUG INDICATION ABT-199 chronic lymphocytic leukemia Imbruvica pancreatic cancer, DLBCL Duvelisib chronic lymphocytic leukemia Elotuzumab multiple myeloma Veliparib NSCLC, breast cancer, ovarian cancer ABT-494 rheumatoid arthritis ABT-493 / ABT-530 hepatitis C Elagolix endometriosis Atrasentan diabetic nephropathy EARLY RESEARCH PROJECTS DRUG INDICATION ABBV-838 multiple myeloma ABT-399 solid tumors BTK Inhibitor autoimmue disorders ABBV-084 systemic lupus erythematosus ABBV-672 Alzheimer's disease ABBV-8E12 progressive supranuclear palsy, Alzheimer's disease ABBV-974 cystic fibrosis DRUGS COMING OFF PATENT DRUG INDICATION YEAR Humira rheumatoid arthritis 2016-2018 Kaletra HIV/AIDS 2016-2018 Biaxin XL bacterial infections 2017 Simcor cholesterol 2017 Niaspan cholesterol 2017 Avicor cholesterol 2017 Vicoprofen pain 2017 TOP SELLING DRUGS DRUG INDICATION 2015 SALES (+/-%) Humira rheumatoid arthritis $14,012 12% Viekira hepatitis C $1,639 n/a Synagis RSV $740 -11% AndroGel testosterone $694 -26% Lupron hormone treatment $826 6% Kaletra HIV/AIDS $700 -20% Imbruvica chronic lymphocytic $754 n/a leukemia Synthroid hyperthyroidism $755 6% Creon digestion $632 23% Sevoflurane anesthesia $474 -14%
AbbVie's revenues increased more than 22%, to $22.8 billion in 2015. The biopharma company has continued to drive significant growth from its leading product Humira, with 2015 sales of $14 billion, an increase of 19% compared to 2014. The company also expanded its flagship therapies to include the HCV franchise and oncology product Imbruvica, a first-in-class BTK inhibitor, which positions AbbVie as an oncology leader. Additionally, during the year AbbVie received FDA approval of Duopa for patients with Fhrkinson's disease in the U.S. AbbVie has a growing number of programs in mid- and late stage development, and it continues to make significant pipeline advancements. During the year, it submitted regulatory submissions for Venetoclax for relapsed/refractory chronic lymphocytic leukemia (CLL); Imbruvica for first-line CLL; Zynbryta for multiple sclerosis; and Humira for uveitis. The company also successfully transitioned several mid-stage pipeline assets into late-stage development, including its JAK1 inhibitor, ABT-494, in rheumatoid arthritis; a pan-genotypic, next-generation HCV combination therapy; elagolix for uterine fibroids; and ABT-414, an antibody drug conjugate for glioblastoma multiforme.
The big news during the year occurred in March when AbbVie announced it was buying Pharmacyclics, a biopharmaceutical company that develops and commercializes novel therapies for cancer treatment. The $21 billion deal closed in May 2015 and expands AbbVie's clinical and commercial presence in oncology giving it ownership of Pharmacyclics' flagship asset Imbruvica, a highly effective treatment for hematologic malignancies.
Imbruvica is a Bruton's tyrosine kinase (BTK) inhibitor approved for four indications to treat three different types of blood cancers including chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom's macroglobulinemia. Imbruvica received FDA approval in 2013 and is the only therapy to have received three Breakthrough Therapy designations by the FDA. It is currently approved in more than 40 countries
Potential further Imbruvica indications include solid tumors, as well as the potential to leverage AbbVie's immunology expertise for the development of Pharmacyclics'immunology program, and advance AbbVie's efforts in hematologic malignancies.
Expanding its manufacturing capabilities, AbbVie announced during the year the expansion of one of its existing sites in Puerto Rico with an estimated investment of $30 million. This expansion will add to Puerto Rico's capabilities as a manufacturing destination for biotechnology and is expected to create as many as 100 new jobs during the next two years. The expansion will take place at AbbVie's site located in the northern municipality of Barceloneta. This site is already home to two of the company's state-ofthe-art facilities.
At the tail end of 2014, AbbVie expanded capacity to support its immunology and oncology pipelines when it acquired a small molecule API manufacturing site in Singapore's Tuas Biomedical Park. AbbVie's first manufacturing facility in Asia, the 120,000 square meter site increases capacity for compounds in its immunology and oncology pipelines. It includes a contained API facility, additional buildings, and ancillary equipment.
AbbVie will also construct a bulk biologies manufacturing facility on the property, which is expected to be operational in 2019. The combined facilities will add more than 250 new employees, including positions across manufacturing, technical operations, administration, quality, IT and supply chain. The company is also renovating its small molecule facility.
On the research front, AbbVie and Calico entered an R&D collaboration to discover, develop and market new therapies for age-related diseases, including for neurodegeneration and cancer. Calico is funded by Google and led by former Genentech executives Arthur Levinson and Hal Barron. Calico will establish a new R&D facility in the San Francisco Bay Area with a focus on drug discovery and early drug development and AbbVie will provide scientific and clinical development support, as well as its commercial expertise. Together, the firms will initially contribute as much as $250 million to fund the collaboration with the potential for an additional $500 million each.
Calico will be responsible for research and early development for the first five years and to advance collaboration projects through Phase Ha for a 10-year period. AbbVie will support Calico in its early R&D efforts and, following Phase Ha studies, will have the option to manage late-stage development and commercial activities.
At the start of 2015 AbbVie opened an Innovation Center on the campus of the University of Illinois Research Fhrk in Urbana-Champaign. The Innovation Center plans to employ more than 18 undergraduate and graduate students on a part-time basis. Eight students have begun working on several AbbVie R&D Information Technology projects, which is the initial focus of work at the center.
Students will work on real-world projects ranging from utilizing visualization software in clinical trial research, to harnessing the power of reporting tools for the identification of additional areas of research, to using informatics, text mining and other analytics software in medical research. An AbbVie site manager will oversee the students and serve as liaison between the AbbVie Innovation Center and the University.
In other news, AbbVie entered a global collaboration and license agreement with Halozyme Therapeutics to develop and commercialize products combining AbbVie compounds with Halozyme's Enhanze platform. Halozyme received $23 million upfront and milestone payments totaling approximately $130 million for as many as nine collaboration targets, as well as royalties if products under the collaboration are commercialized. The Halozyme Enhanze platform is based on a recombinant human hyaluronidase enzyme (rHuPH20) that temporarily degrades hyaluronan, a chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs. For AbbVie, this technology may allow for more rapid delivery of injectable medications through subcutaneous delivery.
Another collaboration saw AbbVie enter into an exclusive worldwide license agreement with C2N Diagnostics to develop and commercialize a portfolio of anti-tau antibodies for the treatment of Alzheimer's Disease and other neurological disorders. Tau stabilizes proteins that are responsible for the structure and transport in neuronal cells. Abnormal accumulation of altered tau protein is a leading indicator in a variety of neurodegenerative conditions including Alzheimer's Disease, Progressive Supranuclear Palsy and Corticobasal Degeneration. In these conditions, the development of tau pathology strongly correlates with clinical disease progression.
At the very beginning of 2016, AbbVie and MD Anderson Cancer Center entered a three-year immunotherapy collaboration to efficiently select and conduct preclinical and clinical studies evaluating new ideas in the area of immuno-oncology. AbbVie's research efforts in immunotherapy leverage the company's strengths in biology, protein engineering and chemistry. MD Anderson's immunotherapy platform includes technology for preclinical modeling, clinical trials and immune monitoring before, during and after treatment to better understand drug mechanisms and identify biomarkers to guide treatment. AbbVie and MD Anderson will each assign two scientists to a joint scientific committee to decide on projects to pursue. The collaboration will initiate with projects driven by AbbVie Biotherapeutics, AbbVie's center of innovation in the biotech hub of the San Francisco Bay Area. Future projects will draw from AbbVie's portfolio of oncology programs.
11 AMGEN Headquarters: Thousand Oaks, CA twitter.com/Amgen www.amgen.com HEADCOUNT: 17,900 YEAR ESTABLISHED: 1980 REVENUES: $21,662 (+8%) NET INCOME: $6,939 (+35%) R&D: $3,917 (-5%) DRUGS APPROVED/LAUNCHED DRUG INDICATION Repatha high cholesterol Kyprolis relapsed multiple myeloma Imlygic unresectable melanoma DRUGS PENDING DRUG INDICATION Enbrel chronic severe plaque psoriasis Blincyto pediatric and adolescent relapsed or refractory B-cell precursor acute lympho-blastic leukemia etelcalcetide secondary hyperparathyroidism DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION AMG 334 prophylaxis of migraine Aranesp myelodysplastic syndromes Kyprolis multiple myeloma who have received at least one prior therapy Parsabiv secondary hyperparathyroidism Prolia glucocorticoid-induced osteoporosis Romosozumab osteoporosis Vectibix wild-type KRAS exon 2 mCRC Xgeva prevention of bone metastases in patients with adjuvant breast cancer EARLY RESEARCH PROJECTS DRUG INDICATION AMG 211 cancer AMG 224 multiple myeloma AMG 228 solid tumors AMG 232 cancer AMG 301 migraine AMG 319 hematologic malignancies AMG 330 acute myeloid leukemia AMG 557 systemic lupus erythematosus AMG 592 inflammatory diseases AMG 820 cancer OPROZOMIB hematologic malignancies DRUGS COMING OFF PATENT DRUG INDICATION YEAR Neulasta rheumatoid arthritis 2017 Sensipar primary 2016 hyperparathyroidism TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Enbrel rheumatoid arthritis $5,364 14% Neulasta neutropenia $4,715 3% Aranesp anemia $1,951 1% Epogen anemia $1,856 -9% Sensipar/Mimpara renal disease $1,415 22% Xgeva bone cancer $1,405 15% Prolia bone cancer $1,312 27% Neupogen neutropenia $1,049 -9% Vectibix colorectal cancer $549 9% Nplate immune thromboytopenia $525 12% Kyprolis multiple myeloma $512 55%
Holding steady at 11 once again this year, Amgen, the grandfather of biopharma, is certainly consistent and key drug approvals for Kyrpolis in multiple myeloma and cholesterol drug Repatha, as well as Imlygic in metastatic melanoma, may help offset some patent losses for key products in the next few years.
Amgen is off to a good start this year. Revenues were up 10% in the first quarter to $5.5 billion, with 7% product sales growth driven by Enbrel (+24%), Prolia (+29%), Aranesp (+11%), Neulasta (+4%), Kyprolis (+43%) and XGEVA (+11%). Earnings were up 17% to $1.9 billion. Overall, Amgen had nine drugs that saw double-digit percentage growth in 1Q16. However, sales of Neupogen were down 13% impacted by the launch of Sandoz's biosimilar Zarxio in the U.S.
The company is challenged with patent expirations for several significant drugs. Biosimilar rivals for Neupogen and Epogen are beginning to hurt sales, and Neulasta will soon face the same fate. Enbrel could also face biosimilar competition soon. Sandoz's biosimilar version of Enbrel is expected to come up before the FDA's Arthritis Advisory Committee next month. The 10-month review process could mean approval by mid 2016, although a launch will depend on the outcome of patent litigation between the two companies. The original patent on Enbrel was set to expire October 2012, but Amgen says it's protected from biosimilar competition until 2029.
Amgen is pursuing the biosimilar market as well with nine biosimilar candidates representing potential annual revenues of more than $3 billion. The company plans to launch its first biosimilar in 2017, and subject to approval, four others through 2019.
The FDA's Arthritis Advisory Committee will review data supporting the company's biologies license application for ABP 501, a biosimilar version of AbbVie's best-selling drug, Humira, and a final decision regarding approval is expected by September 25th. It's also under review in the EU. Humira, used to treat rheumatoid arthritis and a number of other inflammatory diseases, had sales of $14 billion in 2015 and is among the top-selling drug products in the U.S.
Nevertheless, innovative pipeline advances are key to sustaining Amgen's long-term strength. Kyprolis, approved for relapsed multiple myeloma, also got a positive CHMP opinion for expanding the label to include treatment in combination with dexamethasone for patients with multiple myeloma who have received at least one prior therapy. Kyprolis' label was expanded in the U.S. earlier this year for this indication and is well-positioned to gain market share.
Recent analyses from Phase III studies of Kyprolis, a product of Amgen's subsidiary Onyx Pharmaceuticals, showed patients with relapsed multiple myeloma live longer without disease progression. Additional analysis based on a head-to-head trial showed Kyprolis with Lenalidomide and Dexamethasone offers substantial value over previous standard of care, and that Kyprolis and Dexamethasone doubled progression-free survival versus Takeda'sVelcade (Bortezomib) and Dexamethasone.
Also, Repatha was approved last August for the treatment of persistently high LDL cholesterol. Studies showed that patients experienced approximately 65% reduction in LDL-C from baseline to end of study.
As far as cholesterol drugs go, Repatha and Sanofi/Regeneron's Praluent are considered breakthrough therapies for hardto-treat patients and are the first highly effective cholesterollowering medications in a generation. Repatha's cost is $14,100 per year but as the companies are battling it out to gain payer reimbursements, discounts and deals are unfolding. For example, in the U.S. Express Scripts agreed to offer both Praluent and Repatha on its formulary in exchange for discounts, while Praluent will be UnitedHealth Group's "preferred" drug for treating high LDL cholesterol and Amgen won a formulary exclusive with CVS.
Lastly, Imlygic, approved for melanoma, has become the first oncolytic viral therapy approved by the FDA based on therapeutic benefit. Imlygic is derived from a herpes simplex virus that has been genetically engineered to infect cancer cells and cause cell death. While the drug has not been shown to improve overall survival, its unique approach provides another option for treating this complex disease that often requires the use of several therapeutic modalities.
Amgen anticipates the average cost of this novel, first-in-class oncolytic viral therapy to be approximately $65,000 and expects variability of IMLYGIC dosing from patient to patient.
Amgen also has collaborations to study the use of Imlygic in combination with two PD-1 inhibitors, Merck's Keytruda (pembrolizumab) and Roche's atezolizumab (MPDL3280A). With Merck, the combination is being tested in Phase I open-label trials in melanoma and head and neck cancer, and in a Phase III randomized trial in melanoma. The Roche collaboration is studying Imlygic with atezolizumab in a Phase I study in triple-negative breast cancer and metastatic colorectal cancer. Data indicate that combining the two modalities has a synergistic effect, and the combination has a better side effect profile than the combination of two checkpoint inhibitors.
Imlygic joined Amgen's portfolio with the January 2011 acquisition of Biovex Group, a privately held, venture-funded, biopharma company headquartered in Woburn, MA, in a deal worth as much as $1 billion, of which $475 million was paid up front, with additional payments of $575 million based on certain regulatory and sales milestones.
Considering the highly lucrative biosimilars market, competition is certainly intensifying. If Amgen can hold off Enbrel competition, it stands to recoup some losses with its late stage biosimilar assets, as well as advance the twelve Phase III clinical studies currently underway.
12 LILLY Headquarters: Indianapolis, IN twitter.com/EliLillyCo www.lilly.com HEADCOUNT: 41,000 YEAR ESTABLISHED: 1876 REVENUES: $19,959 (+2%) NET INCOME: $2,408 (+1%) R&D: $4,796 (+1%) DRUGS APPROVED DRUG INDICATION Ixekizumab moderate-to-severe plaque psoriasis Jentadueto XR type 2 diabetes Humulin R U-500 severely insulin- resistant diabetes Basaglar type 1 and type 2 diabetes Portrazza metastatic squamous non-small cell lung cancer Synjardy type 2 diabetes Humalog 200 type 1 and type 2 diabetes DRUGS PENDING DRUG INDICATION Baricitinib rheumatoid arthritis Olaratumab advanced sarcoma Empagliflozin cardiovascular outcomes PHASE IIB AND BEYOND DRUG INDICATION Nasal glucagon severe hypoglycemia in diabetes BACE-AZD3293 Alzheimer's disease Galcanezumab cluster headache, chronic and episodic migraine Solanezumab Alzheimer's disease Tanezumab osteoarthritic pain, cancer pain Abemaciclib breast cancer Empagliflozin type 1 diabetes Ramucirumab 2nd line bladder cancer, hepatocellular carcinoma, EGFR positive NSCLC EARLY RESEARCH PROJECTS DRUG INDICATION BAFF/IL-17 immune diseases VEGFR-1 Mab diabetic nephropathy D1 potentiator dementia Met/EGFR bispecific cancer BTK inhibitor immunology N3pG-AB MAb Alzheimer's disease Pan-Rat cancer Pomaglumetad methionil schizophrenia Blosozumab osteoporosis DGAT-2 inhibitor dyslipidemia CSF-1R MAb cancer DRUGS COMING OFF PATENT DRUG INDICATION YEAR Alimta nonsquamous non-small 2016-2017 cell lung cancer Cialis erectile dysfunction 2017 Zyprexa depression 2017 Stmbyax depression 2017 Seroquel XR antipsychotic 2017 TOP SELLING DRUGS DRUG INDICATION 2015 SALES (+/-%) Alimta cancer $2,493 -11 % Humalog diabetes $2,842 2% Cialis erectile dysfunction $2,311 1% Cymbalta anxiety, depression $1,028 -36% Humulin diabetes $1,307 -7% Forteo osteoporosis $1,348 2% Zyprexa schizophrenia $940 -9% Strattera ADHD $784 6% Effient anticoagulant $523 0% Erbitux head and neck cancer $485 30%
In 2015 Lilly returned to revenue growth, led by Cyramza and Trulicity following their launches, with significant contributions from its enlarged animal health business, which got a boost after it completed the acquisition of Novartis Animal Health for $5.28 billion at the start of the year under review. Revenue increased 2 percent to $19.96 billion, with six products topping $1 billion in annual sales.
Lilly also reported positive advances in its pipeline of molecules in clinical development. Highlights include: in diabetes, positive cardiovascular outcomes data for Jardiance; in immunology, four positive Phase III studies on baricitinib and strong Phase III data on ixekizumab; and in oncology, Breakthrough Therapy Designation for olaratumab and abemaciclib, several important business development deals in immuno-oncology, and the approval of Portrazza for the treatment of metastatic squamous non-small cell lung cancer late in the year.
The year was active for Lilly on the collaboration front, which saw it expand already existing agreements and form new alliances as well. With Innovent Biologies, Lilly has in place a plan to develop and commercialize a portfolio of cancer treatments. In 2015 the two companies expanded the drug development collaboration, already one of the largest in China between a multinational and domestic biopharmaceutical company. The companies said they will collaborate to support the development and potential commercialization of up to three anti-PD-1 based bispecific antibodies for cancer treatments over the next decade, both inside and outside of China. Lilly will exercise its rights to develop, manufacture and commercialize these potential cancer treatments outside of China, while Innovent will now have the rights to develop, manufacture and commercialize these potential cancer treatments for China.
Also in China, WuXi PharmaTech (Cayman) and Lilly entered into a strategic collaboration to develop, manufacture and commercialize a novel small molecule.The once-daily oral agent, discovered by Lilly, has the potential to address cardiovascular risk in patients with dyslipidemia. An estimated 276 million patients in China are affected by these conditions. The drug aims to reduce cardiovascular events in patients with elevated LDL cholesterol and triglycerides at high risk of cardiovascular events. WuXi will be responsible for regulatory, development and manufacturing activities in China and Lilly will be responsible for commercial activities. Both companies will invest in this potential new medicine in China. An Investigational New Drug (IND) application will be filed in China by WuXi, and product development and registration will take place within China.
A collaboration agreement was formed with Hanmi to develop and commercialize Hanmi's compound being investigated for the treatment of autoimmune and other diseases. Lilly received rights to the molecule for all indications on a worldwide basis excluding China, Hong Kong, Taiwan, and Korea, and will be responsible for leading development, regulatory, manufacturing, and commercial efforts in our territories.
Another research collaboration with BioNTech aims to discover novel cancer immunotherapies. The companies will collaborate to identify and validate tumor targets and their corresponding T cell receptors (TCRs) in one or more types of cancer. These tumor targets and TCRs may then be engineered and developed into potent and selective cancer therapies.
Lilly entered a global collaboration and license agreement with Halozyme to develop and commercialize products combining its proprietary compounds with Halozyme's Enhanze platform to aid in the dispersion and absorption of other injected therapeutic drugs. For Lilly, this technology may allow for more rapid delivery of injectable medications through subcutaneous delivery.
Toward the end of the year, Lilly and Merck extended an existing collaboration to evaluate the safety and efficacy of the combination of Lilly's Alimta (pemetrexed for injection) and Merck's Keytruda (pembrolizumab) in a Phase III study in first-line non-squamous non-small cell lung cancer (NSCLC). The expansion of this oncology trial collaboration follows encouraging data from a Phase I study, which evaluated pemetrexed, carboplatin and pembrolizumab in first-line nonsquamous NSCLC.
Lilly and AstraZeneca also extended their existing immuno-oncology collaboration exploring novel combination therapies for the treatment of solid tumors. The companies will now evaluate the safety and efficacy of a range of additional combinations across their portfolios. Lilly will lead the studies and both companies will contribute resources. Earlier in the year, the companies entered a Phase I clinical trial collaboration to evaluate the safety and preliminary efficacy of combining durvalumab and ramucirumab as a treatment for patients with advanced solid tumors.
In November Lilly unveiled plans to expand its global R&D headquarters in Indianapolis, IN, adding 130,000 square feet to its existing complex. The $70 million investment will feature a multi-disciplinary lab that facilitates collaboration across multiple research functions. The new building is part of Lilly's continued growth of its Indianapolis footprint, which included a $400 million expansion initiated in 2013 to increase its insulin manufacturing capacity.
When complete in 2017, the new building will enable chemists and engineers to work together a collaboration-centric workspace with modelling, analytical and formulation scientists. The company's strategy incorporates flexible labs that can adapt as research and technology needs evolve, as well as open, interactive meeting spaces that are meant to promote multi-disciplinary problem-solving.
The lab will focus its efforts on small molecules, which currently comprise about half of Lilly's investigational drug portfolio.
In May, Lilly unveiled plans to establish a new drug delivery and device innovation center in Cambridge, MA, which was opened by year's end. The Lilly Cambridge Innovation Center is designed to allow life science organizations to explore how emerging technologies and connectivity can advance drug delivery and device innovation. The center increases the company's delivery and device R&D space by nearly 50% and increasing staff by 25%.
According to the company, the center will serve as a portal for external partnerships and collaboration activities with the company's existing research facilities in San Diego, New York City and Indianapolis. During the year Lilly also said it expanded the San Diego biotech center as well as its presence at the Alexandria Center for Life Science in New York, NY.
More than half of the company's pipeline now comprises biologies that require some type of injection. The company expects its revenues from device-enabled products to double by 2020.
13 TEVA Headquarters: Petach Tivka, Israel twitter.com/tevapharm www.tevapharm.com HEADCOUNT: 42,888 YEAR ESTABLISHED: 1901 REVENUES: $19,652 (-3%) SPECIALTY PHARMA REVENUES: $8,338 (-3%) NET INCOME: $1,597 (-48%) R&D: $1,525 (+2%) DRUGS APPROVED DRUG INDICATION ProAir RespiClick pediatric asthma Cinqair severe asthma DRUGS PENDING DRUG INDICATION Vantrela ER abuse pain deterrent TEV-90109 opioid addiction Copaxone 40mg multiple sclerosis SD-809 Huntington disease Reslizumab IV asthma Fluticasone asthma, COPD Salmeterol Spiromax PHASE IIB AND BEYOND DRUG INDICATION TEV-48125 chronic and episodic migraine TV-46763 pain Laquinimod multiple sclerosis SD-809 Tardive dyskinesia Fluticasone asthma Propionate MDPI Reslizumab SC asthma CEP-41750 chronic heart failure EARLY RESEARCH PROJECTS DRUG INDICATION TV-46139 pain SD-809 Tourette syndrome SD-1077 Parkinson's disease SD-560 Idiopathic pulmonary fibrosis Fluticasone Salmeterol asthma, COPD TEV-46017 COPD TEV-90110 HIV TEV-90111 HIV DRUGS COMING OFF PATENT DRUG INDICATION YEAR Azilect Parkinson's disease 2017 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Copaxone multiple sclerosis $4,023 -5% Treanda cancer $741 -3% ProAir asthma $549 15% Azilect Parkinson's disease $384 -10% Nuvigil insomnia $373 -4% Qvar asthma $392 37%
Generic drug giant Teva reported sales of $19.7 billion in 2015. The company's generics business generated 49% of total revenue and includes tablets, capsules, injectables, inhalants, liquids, ointments and creams. Teva is the leading generic drug company in the U.S. and Europe, with 51% of generic revenues in the United States, 28% in Europe and 21% in ROW markets.
Teva's specialty medicines segment includes several franchises, most significantly in the therapeutic areas of central nervous system (CNS) medicines, such as Copaxone, Azilect, Nuvigil and Zecuity and respiratory medicines such as ProAir HFA and QVAR. The specialty medicines segment was responsible for 42% of total revenue and includes other therapeutic areas, such as oncology and women's health.
The big news during the year came on the heals of a failed bid to buy Mylan. After the deal fell through Teva got back on the acquisition horse and acquired Allergan Generics for $40.5 billion, bringing together two leading generics businesses and catapulting Teva to the top of the generic leader board.
When combined, with Teva's strong generics portfolio, Allergan Generics' generics pipeline, which holds a leading position in first-to-file opportunities in the U.S., further enhances Teva's stated goals of delivering the highest quality generic medicines at the most competitive prices and cultivating the best development pipeline in the industry. The resulting world-class product portfolio will be complemented by an expanded and more efficient global footprint, including leadership positions and strengthened operations, sales and R&D platforms in markets around the world.
The transaction has also bolstered Teva's R&D capabilities in the generics industry, directed at fostering innovation, with approximately 320 combined pending ANDAs in the U.S., including exclusive offerings of approximately 110 U.S. FTF pending ANDAs.
During the year Teva also acquired Representacionese Investigaciones Medicas, S.A. de C.V. (Rimsa), a pharmaceutical manufacturing and distribution company in Mexico, along with a portfolio of products, assets, and companies in Latin America and Europe, for $2.3 billion. Rimsa had $227 million in revenues in 2014 with an annual growth of 11%. The company has an extensive portfolio of specialty products, including fixed-dose combination products. The deal makes Teva a leading pharma company in Mexico, the second largest market in Latin America.
Auspex Pharmaceuticals was also bought by Teva in a deal worth approximately $3.2 billion and expands Teva's CNS franchise. Auspex's lead investigational product, SD-809 (deutetrabenazine), leverages its deuterium technology platform, and is being developed for the potential treatment of chorea associated with Huntington's disease, tardive dyskinesia, and Tourette syndrome. The company expects commercial launch for this indication in 2016.
The year also saw Teva divest several assets. ANI Pharmaceuticals acquired 22 previously marketed generic drug products from Teva for $25 million in cash and a percentage of future gross profits from product sales. The acquisition includes 19 solid-oral dosage products, and three oral suspension products. ANI will initially focus to tech transfer four products that qualify as CBE30 filings into ANI's two manufacturing facilities; these four products have a combined trailing twelve month market value of $210 million, according to IMS Health. The total market value for the 22 products is $650 million on a trailing twelve-month basis, per IMS Health.
In other news, Ignyta, an oncology focused biopharma company, acquired worldwide rights and assets to four of Teva's targeted oncology development programs for approximately $41.6 million.
Several alliances were formed during the year as well. Notably, Teva and Takeda established a new business venture to meet a range of needs for generics in Japan. Japan is among the fastest growing generics markets in the world, driven by social requirements for stable supply of affordable high quality medicines and the Japanese government's policy of reduction of healthcare expenditures. Takeda's strong distribution presence in Japan will combine with Teva's supply chain, operational network, global commercial infrastructure, and R&D.
The business venture will offer patients and the healthcare system the portfolio of Teva's generic medicines and Takeda's products. Teva will have a 51% stake in the new company and Takeda will have 49%. The business venture will operate as an independent company with its own board of directors, chief executive officer, and executive leadership team.
In February 2015, Teva entered into an exclusive license agreement with Eagle Pharmaceuticals for Eagle's EP-3102, a bendamustine hydrochloride rapid infusion product. In December 2015, the FDA approved the product, Bendeka (bendamustine hydrochloride), an injection for the treatment of patients with chronic lymphocytic leukemia (CLL) and for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Teva is responsible for all U.S. commercial activities for the product including promotion and distribution. Bendeka became commercially available in January 2016.
Teva also entered a partnership to explore ways to apply Microchips Biotech's implantable drug delivery device to Teva's portfolio of products to enhance clinical outcomes for chronic drug therapies. Microchips Biotech's electronic device is made up of microchip arrays that can store hundreds of therapeutic doses of drug for periods ranging from months to years and releases each dose at precise times. The device can be programmed to release drug on a pre-determined schedule and will have wireless control features.
The partnership will initially focus on one selected disease area with the option to expand the program into several additional therapeutic areas. As programs advance, Microchips Biotech will receive development and commercial milestone payments and royalties on future product sales. Microchips will also receive funding to develop products for any future additional indications Teva may develop, and Teva will be responsible for Phase II and III development and regulatory filings.
Lastly, Teva entered an agreement to acquire Gecko Health Innovations, a software and product solutions company that aids in compliance and adherence improvement in the management of respiratory diseases. As a result of the deal, Teva gains CareTRx, a cloud-based solution designed to simplify chronic respiratory disease management, connecting patients and caregivers through remote monitoring and real-time adherence tools. Teva will explore ways to apply the CareTRx technology to its pipeline and portfolio of respiratory products with the goal of enhancing clinical outcomes.
14 BRISTOL-MYERS SQUIBB Headquarters: New York, NY twitter, com/bmsnews www.bms.com HEADCOUNT: 25,000 YEAR ESTABLISHED: 1887 REVENUES: $16,560 (+4%) NET INCOME: $1,624 (-19%) R&D: $5,920 (+31%) DRUGS APPROVED DRUG INDICATION Opdivo classical Hodgkin lymphoma, advanced renal cell carcinoma, BRAF advanced melanoma Empliciti multiple myeloma Opdivo + Yervoy advanced melanoma Daklinza genotype 1 or 3 chronic hepatitis C Yervoy cutaneous melanoma Evotaz HIV-1 Nivolumab metastatic squamous non-small cell lung cancer PHASE IIB AND BEYOND DRUG INDICATION Prostvac immuno-oncology IKur Inhibitor cardiovascular PEG-FGF21 (1) fibrotic diseases LPA1 Antagonist fibrotic diseases Pentraxin-2 genetically defined diseases Lulizumab immunoscience EARLY RESEARCH PROJECTS DRUG INDICATION PAR4 Antagonist cardiovascular Factor Xla Inhibitor cardiovascular PEG-FGF21 (2) fibrotic diseases Galectin-3 Inhibitor fibrotic diseases Anti-eTau genetically defined diseases Anti-Myostatin genetically defined diseases Lirilumab (Anti-KIR) immuno-oncology Urelumab (Anti-CD137) immuno-oncology Anti-PD-L1 immunoscience Anti-CD40L immunoscience Mesothelin-ADC oncology Ulocuplumab oncology DRUGS COMING OFF PATENT DRUG INDICATION YEAR Reyataz HIV/AIDS 2018 Sustiva HIV/AIDS 2018 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Orencia rheumatoid arthritis $1,885 14% Eliquis deep vein thrombosis $1,860 n/a and pulmonary embolism Sprycel leukemia $1,620 9% Baraclude hepatitis B $1,312 -9% Sustiva HIV/AIDS $1,252 -13% Franchise Reyataz HIV/AIDS $1,139 -16% Yervoy oncology $1,126 -14% Opdivo melanoma, lung cancer, $942 n/a renal cancer
Investing in the future of its R&D operations is a top priority for Bristol-Myers Squibb (BMS), which recorded sales of $16.56 billion in the year under review. On the R&D front BMS bolstered its organization when it unveiled plans to expand its presence within hubs of scientific excellence and innovation with the opening of a new state-of-the-art research site in Cambridge, MA, in addition to the ongoing expansion of the company's R&D Discovery site in the San Francisco Bay Area.
The new facility in Cambridge is expected to open in 2018 while the ongoing site expansion in the San Francisco Bay Area adds 61,000 square feet of laboratory and office space at the Woodside Technology Park life science campus and is expected to be completed in 2016. Consistent with evolution of the R&D organization's strategic focus, which was previously announced in 2013, the company also discontinued discovery research efforts in virology. BMS made a deal during the year with ViiV Healthcare to divest its pipeline of investigational HIV medicines in various stages of development, for $350 million upfront with potential development and regulatory milestone payments of as much as $518 million for clinical assets and as much as $587 million for discovery and pre-clinical programs.
In Cambridge, Bristol-Myers Squibb scientists will focus on the company's ongoing discovery efforts in genetically defined diseases, molecular discovery technologies and discovery platform chemistry. The company will relocate up to 200 employees from its Wallingford, CN, and Waltham, MA, sites, and a limited number from its central New Jersey locations. As part of this transition, the Waltham site is expected to close in early 2018. The existing site in Wallingford will also close in early 2018 with up to 500 employees relocating to a new location in Connecticut.
The Woodside Technology Park life science campus in the San Francisco Bay Area serves as BMS's Discovery hub for researching breakthrough cancer immunotherapies. The company will fully occupy two of the three buildings at the campus totaling 194,100 square feet and will provide additional capacity to conduct biologies drug discovery research. The site expansion is expected to be completed in 2016.
In other expansion news, at the tail end of 2014 BMS unveiled plans to construct a new large-scale biologies manufacturing facility in Dublin, Ireland to produce multiple therapies for the company's biologies portfolio. Once completed, the investment will in the new facility total nearly $1 billion and will significantly increase BMS's biologies manufacturing capacity and play a central role in its global manufacturing network.
The company's portfolio of approved and investigational biologies covers multiple therapeutic areas including oncology, virology and immunoscience. The 30,000-square meter project will house six 15,000-liter bioreactors and a purification area as well as office and lab space. The plant will be built on the grounds of the company's existing bulk pharmaceutical manufacturing plant and the cost is expected to be comparable to the approximately $900 million investment in the company's biologies manufacturing facility in Devens, MA. Approximately 350 to 400 scientists, engineers, bioprocess operators, quality specialists and other professionals are expected to work at the facility when operational in 2019.
During the year, BMS made a $1.25 billion deal with Promedior to acquire its lead asset PRM-151, a recombinant form of human pentraxin-2 protein in Phase II development for the treatment of idiopathic pulmonary fibrosis (IPF) and myelofibrosis (MF). PRM-151 has been granted Fast Track designation in the U.S. and Orphan designation in the U.S. and Europe for the treatment of MF and Orphan Designation in the U.S. and Europe for the treatment of IPF. Promedior is a clinical stage immunotherapy company developing targeted therapeutics to treat fibrotic diseases. Total aggregate payments to Promedior under the agreement have the potential to reach $1.25 billion, which includes an upfront cash payment for the right to acquire Promedior, an exercise fee payable if Bristol-Myers Squibb elects to exercise its right to acquire the company, and subsequent clinical and regulatory milestone payments.
BMS also acquired Flexus Biosciences, a privately held biotechnology company focused on novel anti-cancer therapeutics, for a potential total consideration of $1.25 billion, including $800 million upfront and development milestones. BMS gains full rights to Flexus'lead preclinical small molecule, F001287, an IDO1-inhibitor targeted for IND filing in 2H15, as well as its IDO/TDO discovery program, which includes its IDO-selective, IDO/TDO dual and TDO-selective compound libraries. A newly formed entity established by the current shareholders of Flexus will retain all non-IDO/TDO assets of Flexus including those related to Phase I FLT3 and CDK4/6 inhibitor, its earlier stage small-molecule Treg cancer immunotherapy programs, and its current personnel and facilities.
BMS bought another private biotech, Cardioxyl Pharmaceuticals, which is focused on the discovery and development of novel therapeutic agents for the treatment of cardiovascular disease. The acquisition gives BMS full rights to Cardioxyl's lead asset CXL-1427, a novel nitroxyl (HNO) donor (prodrug) in Phase II clinical development as an intravenous treatment for acute decompensated heart failure (ADHF). The transaction includes upfront and near-term milestone payments of up to $300 million and potential additional consideration of up to $1.775 billion upon the achievement of certain development, regulatory and sales milestones.
In addition to acquisitions, BMS entered several strategic alliances during the year. Together with Bavarian Nordic it entered an agreement that provides it with an exclusive option to license and commercialize Prostvac, Bavarian Nordic's Phase III prostate-specific antigen (PSA)-targeting cancer immunotherapy in development for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).
Other collaborations include a deal between BMS and uniQure that provides BMS with exclusive access to uniQure's gene therapy technology platform for multiple targets in cardiovascular disease. With the Moffitt Cancer Center BMS entered into a collaboration agreement as part of its Immuno-Oncology Rare Population Malignancy (1-0 RPM) program in the U.S. Also, Five Prime Therapeutics entered into an exclusive worldwide license and collaboration agreement with BMS for the development and commercialization of its colonystimulating factor 1 receptor (CSF1R) antibody program, including FPA008 which is in Phase I development for immunology and oncology indications.
15 BOEHRINGER-INGELHEIM Headquarters: Ingelheim, Germany twitter.com/Boehringer www.boehringer-ingelheim.com HEADCOUNT: 47,501 YEAR ESTABLISHED: 1817 REVENUES: $16,167 (+11%) NET INCOME: $1,723 (+51%) R&D: $3,282 (+13%) DRUGS APPROVED DRUG INDICATION Giotrif squamous cell carcinoma of the Praxbind lung reversal of the anticoagulant effects of dabigatran Spiolto Respimat COPD Synjardy type 2 diabetes Glyxambi type 2 diabetes Vargatef non-small cell lung cancer Jentadueto XR type 2 diabetes Pradaxa prophylaxis of deep venous thrombosis and pulmonary embolism in hip replacement surgery PHASE IIB AND BEYOND DRUG INDICATION Idarucizumab reversal of anticoagulant effect of dabigatran etexilate Afatinib head and neck squamous cell carcinoma Bl 695501 rheumatoid arthritis Bl 695502 non-squamous non-small cell lung cancer Dabigatran etexilate stroke prevention Empagliflozin type 1 and type 2 diabetes Linagliptin type 2 diabetes Nintedanib colorectal cancer Volasertib acute myeloid leukemia Bl 409306 schizophrenia Bl 655066 psoriasis, psoriatric arthritis EARLY RESEARCH PROJECTS DRUG INDICATION Bl 836845 prostate cancer Bl 836826 non-hodgkin lymphoma Bl 836858 acute myeloid leukemia Bl 836909 multiple myeloma Bl 836880 solid tumors DRUGS COMING OFF PATENT DRUG INDICATION YEAR Combivent Respimat COPD 2018 Spiriva COPD 2018 Mirapex restless legs syndrome 2018 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Spiriva COPD $3,882 10% Pradaxa atrial fibrillation $1,406 7% Micardis hypertension $1,044 -12% Trajenta type 2 diabetes $993 43%
Jumping four spots to 15, this year proved more successful for Boehringer Ingelheim, having overcome market challenges with pricing in the U.S. for its top selling drugs, and winning proval of Praxbind, a much needed reversal agent for Pradaxa, which helped boost sales that were beginning to slip in 2014 due to the potential dangers of internal bleeding.
Having been named one of the most innovative companies worldwide in 2015, this research-driven pharmaceutical company ranked among the 100 leading global innovators named by news agency Thomson Reuters. Key efforts to remain highly competitive included the sale of its generics business, U.S. subsidiary Roxane, and at the end of 2015. Also, Boehringer entered strategic negotiations with Sanofi to trade its consumer health care business for Sanofi's animal health business. Shortly thereafter, Boehringer made a strategic investment of .5 billion euros to expands its biopharmaceutical production facility in Vienna.
While the company is pursuing biosimilars, we'll focus on innovative efforts for the sake of space. With looming patent expirations for Boehringer's bestseller, respiratory drug Spiriva, it won't be long before new products are needed to replace future lost sales of the $3.9 billion drug. The significant approval of Praxbind in the U.S. and Europe means that Boehringer now has an agent that reverses the anticoagulant effect of Pradaxa, which is Boehringer's second top seller.
In Boehringer's prime indication area, respiratory diseases, the company gained key product approvals in several countries: Spiriva Respimat for asthma, Spiolto for chronic-obstructive pulmonary disease (COPD) and OFEV, which is used to treat the rare disease idiopathic pulmonary fibrosis (IPF) and has been shown to slow disease progression. A Phase III study of OFEV (Nintedanib) in people with systemic sclerosis and lung fibrosis is underway.
Further, the FDA approved Gilotrif (afatinib) as a new oral treatment option for patients with squamous cell lung cancer, providing a new second-line treatment option for patients with the second largest sub-type of non-small cell lung cancer (NSCLC), representing about 20-30% of cases. Studies showed significantly improved overall survival and progression-free sur vival compared to Genentech's Tarceva (erlotinib). Gilotrif is already approved in more than 60 countries for the treatment of distinct types of EGER mutation-positive NSCLC.
Additionally, a head-to-head study demonstrated Gilotrif significantly improved clinical outcomes compared to AstraZeneca's Iressa (gefitinib) in EGFR mutation-positive advanced nonsmall cell lung cancer.
In metabolic diseases, under the Boehringer/Lilly alliance, the FDA approved Synjardy (empagliflozin and metformin hydrochloride) tablets for the treatment of type 2 diabetes. Synjardy is the third product containing empagliflozin to be approved by the FDA, following Jardiance (empagliflozin) and Glyxambi (empagliflozin/linagliptin).The Synjardy combination uses complementary mechanisms of action to help control blood glucose. Empagliflozin is the only diabetes medication to show a significant reduction in both cardiovascular risk and cardiovascular death in a dedicated outcome trial.
Among late stage assets and alliances, Boehringer and Abb Vie partnered to develop and commercialize BI655066, an anti-IL-23 monoclonal antibody in Phase III development for psoriasis. Boehringer's BI 655066 cleared skin better, faster and for longer than Janssen's Stelara (ustekinumab) in a Phase II psoriasis trial. The companies are also evaluating the drug's potential in Crohn's disease, psoriatic arthritis and asthma.
Boehringer's third generation EGFR TKI, BI 1482694, received FDA Breakthrough Therapy Designation for the treatment of non-small cell lung cancer and has the potential to become a new treatment option for patients. Phase I/II data showed 62% objective responses in patients, including 46% with confirmed tumor response. A new global Phase II trial is enrolling patients.
Additionally, Boehringer expanded its position in lung cancer obtaining exclusive rights from Hanmi Pharmaceutical to HM61713, a novel 3rd generation EGFR targeted therapy. This new partnership aims to achieve market authorization for HM61713 for patients with EGFR mutation-positive NSCLC by 2017 in the U.S.
Some early stage R&D efforts include collaborations with Inventiva, BioMed X, and The University of Texas MD Anderson Cancer Center. The Inventiva alliance is and example of Boehringer's focus on external innovation and aims to develop potential new treatments for idiopathic pulmonary fibrosis and other fibrotic diseases. The BioMed X collaboration aims to identify novel approaches for the treatment psychiatric diseases, and the alliance with MD Anderson Cancer Center will explore new medicines to treat pancreatic ductal adenocarcinoma (PDAC).
Lastly, Boehringer exercised its option under the Oxford Bio Alliance, gaining exclusive rights to an oncology target. This is the second option exercised under the companies' oncology alliance established in 2013. Boehringer appears well positioned to resume steady growth.
16 TAKEDA Headquarters: Osaka, Japan twitter.com/TakedaPharmaDe www.takeda.com HEADCOUNT: 31,328 YEAR ESTABLISHED: 1781 REVENUES: $16,068 (+2%) NET INCOME: $742 (-$1,196 FY14) R&D: $3,075 (-10%) DRUGS APPROVED DRUG INDICATION Leuplin prostate cancer, premenopausal breast cancer Ninlaro relapsed or refractory multiple myeloma Dexilant acid-related diseases Copaxone relapse prevention of multiple sclerosis Vaxem Hib haemophilus influenzae type b vedolizumab ulcerative colitis, Chron's disease DRUGS PENDING DRUG INDICATION Adcetris post-autologous stem cell transplant Hodgkin lymphoma Brintellix major depressive disorder Nesina type 2 diabetes DRUGS COMING OFF PATENT DRUG INDICATION YEAR Actos diabetes 2016 Avandamet type 2 diabetes 2016 Actoplus MET XR type 2 diabetes 2018 Prevacid GERD 2018-2019 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Velcade multiple myeloma $1,440 9% Leuprorelln prostate cancer, breast $1,106 0% cancer, endometriosis Pantoprazole peptic ulcer $896 -3% Lansoprazole peptic ulcer $796 -13% Entyvio ulcerative colitis, $766 58% Crohn's disease Candesartan hypertension $754 -41% Dexilant acid reflux $668 13% Azilva hypertension $525 14% Nesina diabetes $435 5% Colcrys gout $413 -12%
The product liability lawsuits that were pending against Takeda in the U.S., which accused the company of failing to warn users about research that linked the diabetes drug Actos to an increased risk of bladder cancer, was settled for $2.7 billion in April 2015, hopefully resolving the matter for Japan's largest pharma firm. Despite the difficulties created by the Actos suits, the fiscal year under review had many highlights. In gastroenterology, Takeda was granted marketing authorization for Entyvio (vedolizumab) in the U.S. and Europe. Entyvio is a biologic therapy planned and developed for moderate to severe active ulcerative colitis concomitantly with Crohn's disease.
In oncology Takeda received approval from the FDA for an additional indication of Velcade (bortezomib) for the retreatment of adult patients with multiple myeloma who had previously responded to Velcade therapy and relapsed at least six months following completion of prior Velcade treatment. The company also received approval from the FDA for an additional indication ofVelcade for use in previously untreated patients with mantle cell lymphoma. As a promising successor proteasome inhibitor to Velcade, MLN9708 (ixazomib) is now in five Phase in clinical trials for patients with multiple myeloma and relapsed or refractory primary (AL) amyloidosis in Japan, the U.S., and Europe. Takeda was granted Breakthrough Therapy status from the FDA for MLN9708 for the treatment of relapsed or refractory systemic light-chain (AL) amyloidosis.
At the end of 2014 Takeda formed a dedicated global oncology business--Takeda Oncology--headquartered in Cambridge, MA. Comprised of Takeda's global oncology commercial operations, the oncology business unit remains aligned with Takeda's global oncology R&D function, the oncology therapeutic area unit, and Takeda's oncology drug discovery unit. The company is currently investigating compounds across more than 17 forms of cancer, including ixazomib in AL amyloidosis and multiple myeloma as well as alisertib in relapsed/refractory peripheral T-cell lymphoma, recurrent ovarian cancer, and small cell lung cancer, among other malignancies.
On the R&D front, Takeda continued to intensify its focus on external innovation. One important example is the 10-year collaboration agreement between Takeda and the Center for iPS Cell Research and Application (CiRA) of iyoto University into which it entered in April 2015. The agreement is to develop clinical applications of induced pluripotent stem (iPS) cells across multiple therapeutic areas.
With Mersana Therapeutics, Takeda expanded the ongoing collaboration to create Fleximer antibody-drug conjugate (ADC) drug candidates to include additional oncology targets. During the year Takeda also licensed exclusive rights to use ImmunoGen's ADC technology to develop and commercialize targeted anticancer therapeutics for as many as two undisclosed targets with the option to take a license for a third target as well.
In another partnership, Takeda and Teva have established a new business venture to meet a range needs for generics in Japan, which is among the fastest growing generics markets in the world.
17 NOVO NORDISK Headquarters: Bagsvaerd, Denmark twitter.com/novonordisk www.novonordisk.com HEADCOUNT: 41,600 YEAR ESTABLISHED: 1989 REVENUES: $15,801 (+22%) NET INCOME: $5,104 (+32%) R&D: $1,992 (-13%) DRUGS APPROVED DRUG INDICATION Tresiba and Ryzodeg diabetes DRUGS PENDING DRUG INDICATION Xultophy type 2 diabetes Faster-acting insulin type 1 and 2 diabetes aspart N9-GP haemophilia Nonacog beta pegol haemophilia B PHASE IIB AND BEYOND DRUG INDICATION Semaglutide diabetes Oral semaglutide diabetes N8-GP haemophilia Somapacitan growth disorders EARLY RESEARCH PROJECTS DRUG INDICATION LAI287 diabetes LAI287 diabetes OI320GT diabetes AM833 obesity G530L obesity PYY 1562 obesity Concizumab haemophilia DRUGS COMING OFF PATENT DRUG INDICATION YEAR Levemir diabetes 2017 Victoza diabetes 2017 NovoLog diabetes 2017 Norditropin growth hormone 2017 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) NovoRapid diabetes $3,033 7% Levemir diabetes $2,679 15% Victoza diabetes $2,639 20% Human insulins diabetes $1,644 -2% Novo Mix diabetes $1,631 1% Norditropin HGH deficiency $1,145 8%
In 2015 Novo Nordisk unveiled plans for a new $2 billion production facility in Clayton, NC, where construction has since begun. The facility will produce active pharmaceutical ingredients (APIs) for a range of the company's current and future GLP1 and insulin products. When fully operational in 2020, the site will take on production capacity for diabetes care products in the U.S. The new site is adjacent to Novo Nordisk's existing 42,000 square-meter facility, which assembles and packages FlexPen and FlexTouch prefilled insulin devices for the U.S. market.
In other expansion news, Novo Nordisk said it is planning to invest more than 100 million [euro] in production facilities at its site in Chartres, France, in an effort to meet the increasing worldwide demand for its diabetes medicines. The new facilities will be built on Novo Nordisk's existing 31,000 square-meter site in Chartres, which produces a range of the company's insulin products as well as FlexPen, the world's most widely used insulin injection device. The products are exported to more than 40 countries all over the world.
On the product approval front, the big news came when FDA approved Novo Nordisk's weight management drug Saxenda (ligraglutide 3mg). The drug is being touted as the first once-daily human glucagon-like peptide-1 (GLP-1) analogue for the treatment of obesity. Saxenda is indicated as an adjunct to a reduced-calorie diet and exercise for chronic weight management in obese adults or who are overweight with at least one weight-related comorbidity such as type 2 diabetes and cardiovascular disease. Phase III trial data showed that Saxenda, in combination with a reduced-calorie diet and increased physical activity, resulted in significantly greater weight loss than diet and physical activity alone.
In R&D alliances, Novo Nordisk and Ablynx entered into a global exclusive collaboration and licensing agreement to discover and develop novel multi-specific Nanobody drug candidates for use in an undisclosed disease area, with an option to expand the agreement to include a second nanobody program. Ablynx received an upfront license fee of 5 million [euro] and up to 4 million [euro] in research funding during the initial three-year research term of the collaboration. If Novo Nordisk decides to exercise the option to the second program, the company will pay Ablynx an exercise fee of 4 million [euro]
In another deal, XOMA Corporation licensed the global development and commercialization rights to its XMetA program of allosteric monoclonal antibodies that up-regulate the insulin receptor to Novo Nordisk. XOMA retains commercialization rights for rare disease indications. Novo Nordisk has an option to add these additional rights in rare diseases to its license. XOMA received $5 million in an upfront payment, and the agreement includes up to $290 million in additional milestones. XOMA is also eligible to receive tiered royalties on product sales.
18 ALLERGAN Headquarters: Dublin, Ireland twitter.com/Allergan www.allergan.com HEADCOUNT: 31,200 YEAR ESTABLISHED: 2015 REVENUES: $15,071 (+124%) NET INCOME: $3,683 (-$1,630 FY14) R&D: $2,359 (+289%) DRUGS APPROVED DRUG INDICATION Juvederm Volbella XC perioral lines Byvalson hypertension Teflaro acute bacterial skin and skin structure infections, pediatric Botox Vista crow's feet lines Aczone acne vulgaris Botox lower limb spasticity Viberzi irritable bowel syndrome with diarrhea Avycaz complicated intra-abdominal infections DRUGS PENDING DRUG INDICATION linaclotide chronic idiopathic constipation oxymetazoline HCI persistent facial erythema cream 1.0% DRUGS COMING OFF PATENT DRUG INDICATION YEAR Zymaxid antibiotic 2016 Aczone acne 2016 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Botox chronic migraine, $656 n/a overactive bladder Restasis dry eye $365 n/a Lumigan ocular hypertension $192 n/a Namenda XR Alzheimer's disease $190 27% Delzicol/Asacol ulcerative colitis $163 3% Bystolic hypertension $169 10% Alphagan/ glaucoma, $139 n/a Combigan ocular hypertension Linzess/ irritable bowel syndrome $131 39% Constella
In 2014 after Actavis acquired Allergan in a mega deal worth $66 billion it adopted the Allergan name. The deal was completed in March 2015 and the company's portfolio was bolstered by the addition of Legacy Allergan's therapeutic franchises in ophthalmology, neurosciences and medical aesthetics/dermatology/plastic surgery complementing the its existing central nervous system, gastroenterology women's health and urology franchises.
The combined company benefited from Legacy Allergan's global brand recognition and consumer awareness of key products, including Botox and Restasis. The transaction also expanded the its presence and market and product reach across many international markets, with strengthened commercial positions across Canada, Europe, Southeast Asia and other high-value growth markets, including China, India, the Middle East and Latin America.
The year will be remembered more though for the proposed merger of Pfizer and Allergan in November for a whopping $160 billion, a deal that would have created the largest pharma company in the world. But, the deal didn't go through. It was called off at the last minute after a change in U.S. tax law and is discussed in more detail in Pfizer's profile at the beginning of this report.
However, there were several other deals of note that did go through. One was the acquisition of Kythera Biopharmaceuticals for $2.1 billion. Kythera is focused on the discovery, development and commercialization of novel prescription aesthetic products. Its lead product, Kybella injection, is the first and only FDA-approved, non-surgical treatment for moderate to severe submental fullness, commonly referred to as double chin.
In another deal, Allergan acquired Auden Mckenzie, a company specializing in the development, licensing and marketing of niche generic medicines and proprietary brands in the UK and across Europe for approximately $500 million. The acquisition of Auden Mckenzie makes Actavis the number one supplier of generic pharmaceuticals in the UK and gives the company the number three position in the supply of UK pharmaceuticals.
With Ironwood Pharmaceuticals, Allergan struck a deal to acquire rights to Constella (linaclotide) in the EU, Switzerland, Turkey.
Allergan also acquired certain products in early stage development from Naurex, $571 million plus future contingent payments up to $1.1 billion. The deal expands Allergan's pipeline with Naurex's two leading product candidates GLYX-13 and NRX-1074, two compounds that utilize NMDA modulation as a potential new approach to the treatment of major depressive disorder (MDD).
Lastly, the company entered into an agreement with Merck to acquire the exclusive worldwide rights to Merck's early development stage investigational small molecule oral calcitonin gene-related peptide receptor antagonists, which are being developed for the treatment and prevention of migraines for $250 million. Additionally, Merck is owed contingent payments based on commercial and development milestones of up to $965 million as well as royalties.
During the year Allergan entered into an exclusive licensing agreement with Mimetogen Pharmaceuticals, a clinical stage biotechnology company, to develop and commercialize tavilermide (MIM-D3), a topical formulation of a novel small molecule TrkA agonist for the treatment of dry eye disease.
19 BAYER Headquarters: Leverkusen, Germany twitter.com/Bayer www.bayerpharma.com HEADCOUNT: 111,800 YEAR ESTABLISHED: 1971 REVENUES: $50,611 (+12%) PHARMA REVENUES: $15,017 (+13%) NET INCOME: $4,490 (+20%) R&D: $2,549 (+12%) DRUGS APPROVED DRUG INDICATION Gadavist injection contrast agent Xofigo prostate cancer with bone metastases Kovaltry hemophilia A Eylea secondary to myopic choroidal neovascu- larization, retinal vein occlusion Xarelto secondary prevention of pulmonary throm- boembolism Finacea pustules of mild to moderate rosacea DRUGS PENDING DRUG INDICATION LCS-16 five-year contraceptive DRUGS COMING OFF PATENT DRUG INDICATION YEAR Kogenate antihemophilic factor 2017 Avelox antibiotic 2019 Levitra erectile dysfunction 2018 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Xarelto atrial fibrillation $2,460 34% Eylea macular degeneration $1,342 62% Kogenate hemophilia $1,262 4% Mirena women's health $1,058 18% Nexavar oncolgy $975 15% Betaferon multiple sclerosis $900 flat Yaz women's health $771 -8% Adalat hypertension $692 8% Aspirin Cardio cardiovascular $572 8% Glucobay diabetes $571 18%
Sales of Bayer's pharmaceuticals segment climbed nearly 10 percent in 2015 driven by five recently launched products--Xarelto, Eylea, Stivarga, Xofigo and Adempas.
At the end of the year, the company established its new Bayer Life Science Center. This strategic innovation unit has been designed to help uncover, encourage and unlock breakthrough cross-species technologies and know-how for Bayer by enabling collaborations with entrepreneurial best-in-class companies. The first of these partnerships is a joint venture with Crispr Therapeutics AG, a company specialized in utilizing the new crispr-cas9 gene editing technology.
The partnership will focus on the discovery, development and commercialization of therapeutics for blood disorders, blindness and congenital heart disease. Crispr Therapeutics will contribute its crispr-cas9 gene-editing technology and intellectual property, while Bayer will provide protein engineering expertise and relevant disease knowledge.
The joint venture will be based in London, UK, with operations in Cambridge, MA. This long-term strategic partnership represents the first of its kind investment in the development of target delivery systems in an effort to bring systemic in vivo crispr-cas9 gene editing technology applications to patients.
This is the first investment by the newly established Bayer LifeScience Center, which operates as a strategic innovation unit within Bayer aimed at discovering scientific and medical break throughs more rapidly by enabling innovative partnerships. Bayer will provide a minimum of $300 million in R&D investments during the next five years and will acquire a minority stake in Crispr Therapeutics for $35 million.
During the year Bayer and The Johns Hopkins University entered into a five-year collaboration agreement to develop new ophthalmic therapies targeting retinal diseases. The partners will jointly work on the discovery and development of innovative drugs for the treatment of serious back-of-the-eye diseases that affect many people worldwide, including age-related macular degeneration (AMD), diabetic macular edema (DME), geographic atrophy, Stargardt's disease, and retinal vein occlusion (RVO).
Bayer also licensed a thrombosis drug from Ionis and as part of the deal will assume clinical development and commercialization of it as well. The deal relates to Isis-FXIRx, an antisense investigational drug in development for the prevention of thrombosis. Bayer will further develop and commercialize Isis-FXIRx in areas of high unmet medical need.
Bayer Healthcare and Aronora entered a strategic alliance to manufacture Aronora's AB-022 compound for the treatment of cardiovascular diseases.
In other news, Bayer unveiled plans to invest $100 million in its Berkeley, CA manufacturing site to build a product testing facility that will support the next generation of treatments for hemophilia A.
20 MERCK KGAA Headquarters: Darmstadt, Germany twitter.com/emdserono www.merck.de HEADCOUNT: 50,000 YEAR ESTABLISHED: 1668 REVENUES: $14,034 (+13%) NET INCOME: $1,218 (-4%) R&D: $1,867 (flat) DRUGS APPROVED DRUG INDICATION DRUGS PENDING DRUG INDICATION Cladribine Tablets relapsing-remitting multiple sclerosis PHASE IIB AND BEYOND DRUG INDICATION Avelumab non/small cell lung cancer, gastric cancer, bladder cancer, ovarian cancer platinum resistant/ refractory, renal cell carcinoma EARLY RESEARCH PROJECTS DRUG INDICATION Tepotinib solid tumors M2698 solid tumors M7824 solid tumors M3814 solid tumors M1095 psoriasis M2951 systemic lupus erythematosus DRUGS COMING OFF PATENT DRUG INDICATION YEAR Serostim HIV 2016 Saizen growth hormone deficiency 2016 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Rebif multiple sclerosis $1,964 -11% Erbitux oncology $982 -2% Gonal-f fertility $748 4% Concor cardiovascular disease $506 9% Glucophage type 2 diabetes $477 20% Euthyrox hormone therapy $341 5%
Merck KGaA strengthened its drive to become a leading oncology company by taking full promotional responsibility for Erbitux (cetuximab) in Japan in 2015. The move ended the co-promotion agreement it had with Bristol-Myers Squibb. Merck KGaA said expanding its oncology presence in Japan is an important strategic step along achieving its long-term goal to become a leading global player in oncology and immune-oncology. The transfer of promotional responsibilities for Erbitux in Japan further increases the presence of the company in this strategic market, where it has already positioned Japan as its regional research and development hub for South East Asia.
Also during the year, Merck KGaA and Pfizer finalized an agreement allowing the companies to co-promote Pfizer's anaplastic lymphoma kinase (ALK) inhibitor Xalkori (crizotinib), the first ALK inhibitor approved in the U.S., Japan and the EU. The drug is supported by two positive global randomized trials in the first- and second-line ALK-positive advanced non^small cell lung cancer (NSCLC) treatment settings. Globally more than 8,000 patients have been treated with Xalkori, including those who received Xalkori in clinical trials. This co-promotion relationship is related to the announcement in November 2014 of a global strategic alliance between Merck KGaA and Pfizer to jointly develop and commercialize avelumab, an investigational anti-PD-L1 monoclonal antibody. The immuno-oncology alliance will also advance Pfizer's PD-1 antibody.
By the end of 2015, the two companies had advanced clinical development program with two additional Phase III trials of avelumab. The Javelin Ovarian 200 trial is the first Phase III study of a PD-L1 inhibitor investigated as a treatment for platinum resistant/refractory ovarian cancer. The alliance also announced that the FDA provided approval to move forward with a Phase III study of avelumab as a maintenance treatment, in the first-line setting, in patients with locally advanced or metastatic urothelial cancer.
The clinical development program for avelumab now includes more than 1,500 patients who have been treated across more than 15 tumor types, including breast cancer, gastric/gastro-esophageal junction cancers, head and neck cancer, melanoma, Merkel cell carcinoma, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and urothelial (bladder) cancer. The alliance has initiated six pivotal trials, reaching its goal for 2015, with additional trials expected to initiate in 2016.
Also on the regulatory front, Merck KGaA was granted Fast Track designation for the development of evofosfamide (previously known as TH-302), administered in combination with gemcitabine, for the treatment of previously untreated patients with metastatic or locally advanced unresectable pancreatic cancer. Evofosfamide is an investigational hypoxia-activated prodrug thought to be activated under severe tumor hypoxic conditions, a feature of many solid tumors. The compound, currently in Phase III trials, is being developed in collaboration with Threshold Pharmaceuticals.
21 OTSUKA Headquarters: Tokyo, Japan www.otsuka.com HEADCOUNT: 28,000 YEAR ESTABLISHED: 1921 REVENUES: $11,993 n/a * NET INCOME: $698 n/a R&D: $1,668 n/a DRUGS APPROVED DRUG INDICATION E Keppra epilepsy Onzetra Xsail acute migraine Lonsurf colorectal cancer DRUGS PENDING DRUG INDICATION Abilify autism Samsca hepatic edema, cardiac edema, autosomal dominant polycystic kidney disease TAC-202 allergic rhinitis OPC-1085EL glaucoma PHASE IIB AND BEYOND DRUG INDICATION Abilify Maintena agitation associated with dementia of the Alzheimer's type, Bipolar I Rexulti major depressive disorder, schizophrenia, agitation associated with dementia of the Alzheimer's type, posttraumatic stress disorder Lu AE58054 Alzheimer's disease ASC-01 major depressive disorder AVP-923 dyskinesia associated with Parkinson's disease AVP-786 agitation associated with dementia of the Alzheimer's type Lu AA36143 lowering alcohol consumption of alcohol dependence TS-1 uterocervical cancer TAS-118 pancreatic cancer, gastric cancer SATIVEX cancer pain SGI-110 acute myeloid leukemia Deltyba multi-drug-resistant tuberculosis OPC-12759E dry eyes TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Abilify schizophrenia $2,883 -31 % Pletaai /Mucosta anti-platelet agent / $393 -11 % gastritis, gastric ulcers Abilify Maintena schizophrenia $335 136% * Due to a change in the fiscal year end to December 2014, percentage changes compared to the previous fiscal year are not applicable.
At the very end of 2014 Otsuka made a move to expand its portfolio and expertise in psychiatric diseases with the $3.5 billion acquisition of Avanir, a Southern CA-based biopharma company specialized in central nervous system (CNS) diseases.
Avanir developed and launched Nuedexta (dextromethorphan hydrobromide/quinidine sulfate) in the U.S. in 2011 as the first and only approved treatment for the neurologic disease pseudobulbar affect (PBA). Sales of Nuedexta in fiscal year 2013 were $94 million, a 50% increase for the year. The acquisition also gives Otsuka the late-stage investigational compound AVP-786 in clinical development to treat agitation associated with Alzheimer's disease, and Avanir's clinical development and commercial expertise in neurologic diseases, which supports Otsuka's expansion strategy in psychiatric diseases.
Otsuka kicked off 2015 by established a presence in Australia with a new office in Sydney as part of an effort to build a larger, long-term presence in Australia and Oceania. These regions have been experiencing single-digit percentage growth in the past several years and were estimated at approximately $13 billion in 2012.
While Otsuka focuses on the development of new drugs for CNS such as schizophrenia, depression and Alzheimer's disease, it said these are areas where patients in Australia and elsewhere need better treatments.
The opening in Australia represents Otsuka's 27th affiliate outside Japan, an important milestone the company said as it continues its mission to expand around the globe.
On the product front, during the year Otsuka's schizophrenia treatment Abilify was granted approval in Japan for a new formulation. Ability extended-release injectable suspension, for intramuscular use, is administered to the patient just once every four weeks. It first became available to patients in the U.S. in March 2013 and is also available in 18 European countries, starting with the UK in 2014.
Also during the year, the FDA approved Rexulti (brexpiprazole) as an adjunctive therapy for the treatment of adults with major depressive disorder (MDD) and as a treatment for adults with schizophrenia. Rexulti was discovered by Otsuka and codeveloped with H. Lundbeck A/S. It will be co-marketed by the two companies and is currently available to patients in the U.S.
At the end of the year, Otsuka and UCB Japan announced the launch of E Keppra for IV Drip Infusion 500 mg (levetiracetam) in Japan. Like its oral formulations, E Keppra IV Drip Infusion will be indicated for partial-onset seizures in epilepsy patients as a temporary alternative when they are unable to ingest oral formulations.
22 BIOGEN Headquarters: Cambridge, MA twitter.com/biogenidec www.biogenidec.com HEADCOUNT: 7,350 YEAR ESTABLISHED: 2003 REVENUES: $10,764 (+11%) NET INCOME: $3,547 (+21%) R&D: $2,013 (+6%) DRUGS APPROVED DRUG INDICATION Zinbryta once-monthly relapsing forms of multiple sclerosis Alprolix haemophilia B Elocta (rFVIIIFc) haemophilia A DRUGS PENDING DRUG INDICATION Tysabri disease modifying therapy for relapsing-remitting multiple sclerosis DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION Aducanumab Alzheimer's disease Nusinersen spinal muscular atrophy Obinutuzumab front-line diffuse large B-cell lymphoma, front-line Indolent non-Hodgkin's lymphoma Ocrelizumab primary progressive and relapsing multiple sclerosis Amiselimod inflammatory bowel disease BG00011 idiopathic pulmonary fibrosis Opicinumab multiple sclerosis EARLY RESEARCH PROJECTS DRUG INDICATION BIIB054 Parkinson's disease BIIB059 systemic lupus erythematosus BIIB061 multiple sclerosis BIIB063 Sjogren's syndrome BIIB065 myotonic dystrophy BIIB067 SOD-1-amyotrophic lateral sclerosis Dapirolizumab pegol systemic lupus erythematosus DRUGS COMING OFF PATENT DRUG INDICATION YEAR Tysabri multiple sclerosis 2017-2020 Tecfidera multiple sclerosis 2018 Gilenya multiple sclerosis 2019 TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Avonex multiple sclerosis $2,630 -13% Tecfidera multiple sclerosis $3,638 25% Tysabri multiple sclerosis $1,886 -4% Plegridy multiple sclerosis $339 n/a
Coming off another great year, Biogen continued its growth in 1Q16 with revenues up 7% to $2.7 billion and earnings of $971 million, up 18%. Growth was driven by Tecfidera, up 15% to $946 million, Eloctate sales of $108 million, and Alprolix sales of $75 million. While revenues were partially offset by a 19 % drop in Avonex sales, Tysabri brought in $477 million, up 3 %.
Among recent pipeline advances, Biogen and AbbVie won FDA approval for Zinbryta (daclizumab), a new once-monthly, self-administered, subcutaneous treatment for relapsing forms of multiple sclerosis (RMS). Zinbiyta significantly reduced the annualized relapse rate, the primary endpoint of studies, by 45% compared to Avonex and by 54% compared to placebo.
EU approval for Zinbryta is on the horizon as well and some analysts expect the drug to reach peak sales of around $500 million. While Zinbryta offers greater convenience, Biogen already markets its every-two-weeks MS treatment Plegridy, approved in 2014, and both drugs will compete with Avonex.
Biogen's MS franchise is not without its challenges. Tecfidera, despite impressive sales, has seen a slowing growth rate, and earlier this year Europe revoked one of its key patents. Biogen is appealing the decision but stands to lose as much as $1 billion in annual sales if it fails.
On the biosimilar front, Biogen won key approvals in the EU for Flixabi, an infliximab biosimilar referencing Remicade, developed by the joint venture Samsung Bioepis, and Benepali, the first Etanercept biosimilar referencing Enbrel.
Among Biogen's late-stage assets, Aducanumab, its investigational drug for early Alzheimer's disease was accepted into the EMA PRIority MEdicines (PRIME) program, and is currently being evaluated in two global Phase III studies for safety and efficacy in slowing cognitive impairment and disease progression.
Finally, Biogen recently unveiled plans to spin off its hemophilia business as part of an effort to focus on neurology therapies. In January, Biogen and development partner Sobi received EU approval for ELOCTA for the treatment of haemophilia A, and in May, Alprolix, an extended half-life therapy for haemophilia B was approved. The two drugs, previously approved in the U.S., had combined revenues of $640 million during the twelvemonth period ended March 31, 2016. Biogen says the spin-off will result in two lean, profitable companies. CP
23 MYLAN Headquarters: Canonsburg, PA twitter.com/MylanNews www.mylan.com HEADCOUNT 35,000 YEAR ESTABLISHED 1970 REVENUES: $9,363 (+22%) SPECIALTY SEGMENT: $1,205 (+2%) NET INCOME: $848 (-9%) R&D: $672 (+15%) Dey, Mylan's specialty business, focuses on respiratory, allergy and psychiatric therapies. Its flagship product is EpiPen Auto-Injector, which treats anaphylaxis; the product is the No. 1 prescribed auto-injector with over 90% market share in the U.S. and worldwide. DRUGS PENDING DRUG INDICATION abacavir/lamivudine HIV-1 infection in pediatric patients
After a failed bid for Perrigo, Mylan moved forward with a $9.9 billion deal to merge with Swedish pharma company Meda, boosting its range of branded and generic pharmaceuticals. The deal also gives Mylan a better position in the market for over-the-counter (OTC) medicines. After the deal goes through, the Mylan/Meda OTC business will have sales of around $1 billion per year.
OTC medicines have become an attractive area of the pharma industry as their growth has outstripped the prescription drug sector, mainly driven by emerging markets. Meda's key products including allergy therapy Dymista (azelastine/fluticasone) and Elidel (pimecrolimus) for dermatitis and eczema are set to benefit from Mylan's greater international scale. The deal reduces Mylan's reliance on generic drugs with the addition of specialty brands that are less prone to pricing pressure and competition.
During the year, the company, through its Indian subsidiary Mylan Laboratories, acquired certain female health care businesses, including Jai Pharma, from Famy Care, a specialty women's health care company with global leadership in generic oral contraceptive products (OCPs) for $800 million.
The acquisition builds on Mylan's existing partnerships with Famy Care in North America, Europe and Australia, and provides Mylan with an enhanced and now vertically integrated platform that will accelerate the company's growth in the global women's health care space. This transaction especially complements Mylan's acquisition of Abbott's non-U.S. developed markets specialty and branded generics business, which also includes women's health care portfolio and sales and marketing capabilities. Additionally, the acquisition of the Famy Care businesses will make Mylan a hormonal contraceptives leader in high-growth emerging markets around the world.
In another deal announced in 2015, Renaissance Acquisition Holdings, a portfolio company of private equity firm RoundTable Healthcare Fhrtners, sold its topical pharmaceutical business to Mylan for $1 billion. The topical division is a specialty pharmaceutical business focused on the manufacture, development, sales and marketing of branded and generic topical pharmaceutical products. RoundTable started Renaissance in 2010 when it acquired two contract manufacturing and development organizations, Confab Laboratories and DPT Laboratories. Renaissance, through significant investments in senior leadership, product acquisitions, R&D, capital expenditures, and the development of a pipeline of more than two dozen topical ANDAs and NDAs, has developed into one of the largest, privately-held, specialty pharmaceutical companies in the topicals/dermatology market in North America.
At the beginning of 2016, Mylan entered into an exclusive global collaboration agreement with Momenta Pharmaceuticals to develop, manufacture and commercialize six of Momenta's biosimilar candidates, including abatacept (Bristol-Myers Squibb's rheumatoid arthritis drug Orencia), which had $1.9 billion in sales in 2015.
Momenta received $45 million up front and as much as $200 million in milestone-related payments, with each company sharing the costs and profits for the products. The companies will be jointly responsible for product development, and Mylan will lead worldwide commercialization.
This collaboration builds upon Mylan's existing biologies and insulin analog partnership with Biocon, which includes six biosimilar programs (trastuzumab, pegfilgrastim, adalimumab, bevacizumab, etanercept and filgrastim) and three insulin analogs (glargine, lispro and aspart). Five of these biosimilar programs have successfully completed Phase I trials, and four are in Phase III development. Mylan and Biocon plan on submitting three biosimilar applications and one insulin application in the U.S. and Europe in 2016.
Also on the biosimilar front, during the year Mylan launched the first biosimilar to GlaxoSmithKline's Seretide Evohaler (salmeterol xinafoate/fluticasone propionate) under the name Sirdupla in the UK. Sirdupla is a pressurized metered-dose inhaler (pMDI) indicated to treat symptoms of asthma. 3M Drug Delivery Systems will manufacture the product, which is available in 125/25 meg and 250/25 meg with 120 doses.
In another development and commercialization deal, Mylan and Theravance Biopharma partnered on TD-4208, a novel investigational once-daily nebulized long-acting muscarinic antagonist (LAMA) for chronic obstructive pulmonary disease (COPD) and other respiratory diseases. TD-4208 has shown positive results in COPD in multiple Phase II studies, and the design of the Phase III registrational program for 2016.
24 CELGENE Headquarters: Summit, NJ twitter.com/celgene www.celgene.com HEADCOUNT: 7,000 YEAR ESTABLISHED: 1986 REVENUES: $9,256 (+21%) NET INCOME: $1,602 (-20%) R&D: $3,697 (+52%) DRUGS APPROVED DRUG INDICATION Revlimid Plus newly diagnosed multiple myeloma Dexamethasone Vidaza acute myeloid leukaemia DRUGS PENDING DRUG INDICATION Revlimid mantle cell lymphoma: relapsed/refractory Abraxane gastric: metastatic DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION Revlimid multiple myeloma maintenance, diffuse large B-cell (ABC- subtype): first-line CC-486 lower-risk myelodysplastic syndromes Vidaza post-induction AML maintenance Istodax peripheral T-cell lymphoma: first-line Abraxane pancreatic cancer: adjuvant Otezla psoriasis/PSA, ankylosing spondylitis ozanimod relapsing multiple sclerosis EARLY RESEARCH PROJECTS DRUG INDICATION durvalumab multiple myeloma CC-486 myelodysplastic syndromes EPZ-5676 acute myeloid leukemia CC-122 Indolent lymphoma CC-486 lymphoma AG-120 solid tumors CC-90003 solid tumors PNK-007 acute myeloid leukemia DRUGS COMING OFF PATENT DRUG INDICATION YEAR Revlimid multiple myeloma 2018 Thalomid multiple myeloma, 2018 Hansen's disease TOP SELLING DRUGS 2015 DRUG INDICATION SALES (+/-%) Revlimid multiple myeloma, $5,801 17% mantle cell lymphoma Abraxane breast, lung, $968 14% pancreatic cancer Pomalyst multiple myeloma $983 45% Vidaza myelodysplastic syndrome $591 -4% Otezla psoriasis $472 n/a
Committed to expanding a sustainable pipeline of cancer treatments Celgene Corporation acquired privately held Quanticel Pharmaceuticals, a biotechnology company focused on cancer drug discovery. Celgene bought Quanticel for $100 million upfront with an additional $385 million paid out upon research, development, and regulatory advances related to Quanticel's research and development platform.
Through the agreement, Celgene will have full access to Quanticel's proprietary platform for the single-cell genomic analysis of human cancer, as well as Quanticel's lead programs that target specific epigenetic modifiers to advance Celgene's pipeline of innovative cancer therapies.
The acquisition culminates a 2011 strategic alliance between the two companies. Over the course of the three-and-a-half year alliance, Quanticel industrialized its single-cell platform for analysis of tumor cellular content and applied it to novel target discovery and the generation of high-quality drug candidates. Multiple drug candidates from Quanticel are expected to enter the clinic in 2016.
In another deal during the year, Celgene expanded its inflammation and immunology portfolio with the acquisition of Receptos for roughly $7.2 billion. The acquisition expands its inflammation and immunology portfolio with the addition of Ozanimod, an oral, selective sphingosine 1-phosphate 1 and 5 receptor modulator (SIP), to its pipeline of potential disease-altering medicines and investigational compounds.
Clinical studies of Ozanimod have demonstrated several areas of potential advantage over existing oral therapies for the treatment of ulcerative colitis (UC) and relapsing multiple sclerosis (RMS), including its cardiac, hepatotoxicity and lymphocyte recovery profile.
To develop small molecule therapeutics in oncology, inflammation and immunology and immune-oncology, Celgene partnered with Nurix during the year. In an R&D alliance set up to discover and develop therapeutics for ulcerative colitis and Crohn's disease, Celgene teamed up with Inception IBD, a Quebec-based biotechnology company, and Inserm Transfert Initiative, created under the initiative of Inserm, the French National Institute of Health and Medical Research.
25 DAIICHI SANKYO Headquarters: Tokyo, Japan www.daiichisankyo.com HEADCOUNT: 18,434 YEAR ESTABLISHED: 2005 REVENUES: $8,770 (+7%) NET INCOME: $715 (-75%) R&D: $1,855 (+9%) DRUGS PENDING DRUG INDICATION Edoxaban atrial fibrillation, venous thromboembolism Hydromorphone cancer pain extended- release and immediate- release formulations acute pain CL-108 prevention of seasonal Influenza VN-100 PHASE IIB AND BEYOND DRUG INDICATION Tivantinib hepatocellular cancer Denosumab breast cancer adjuvant, rheumatoid arthritis Nimotuzumab gastric cancer Quizartinib newly diagnosed AML patients Pexidartinib/PLX3397 tenosynovial giant cell tumor Prasugrel ischemic stroke Mirogabalin fibromyalgia, diabetic peripheral neuro pathic pain CHS-0214 rheumatoid arthritis VN-0105 prevention of pertussis, diphtheria, teta- nus, poliomyelitis and Hib VN-0107/MEDI3250 prevention of seasonal influenza EARLY RESEARCH PROJECTS DRUG INDICATION DS-3032 solid cancer, lymphom, leukemia PLX7486 solid cancer DS-3201 non-Hodgkin's lymphoma PLX73086/AC708 tenosynovial giant cell tumor PLX51107 hematologic malignancies DS-1040 acute ischemic stroke DS-2330 hyperphosphatemia in chronic kidney disease DS-9231/TS23 thrombosis DS-9001 dyslipidemia DS-1971 chronic pain DS-1501 osteoporosis DS-7080 neovascular age-related macular degeneration DS-2969 Clostridium difficile infection DS-5141 Duchenne muscular dystrophy VN-0102/JVC-001 prevention of seasonal influenza DRUGS COMING OFF PATENT INDICATION DRUG YEAR hypertension Tribenzor (Olmesartan) 2016 TOP SELLING DRUGS INDICATION 2015 DRUG SALES (+/-%) hypertension Olmesartan cholesterol, type 2 diabetes $2,526 -3% Welchol platelet inhibitor $403 -7% Prasugrel iron deficiency $286 29% Venofer platelet inhibitor $260 0% Effient $173 8%
Daiichi Sankyo unveiled plans during the year to overhaul its U.S. operations, saying the company was transitioning from a maturing primary care product portfolio to a differentiated specialty portfolio including areas such as cardiovascular, pain management and oncology.
To reduce expenses, the company eliminated 1,000 to 1,200 positions across the U.S. commercial function located in Earsippany, NJ, as well as field-based sales and other positions throughout the country. The reorganization does not include U.S.-based R&D functions, which have staff concentrated in Edison, NJ, or its packaging plant in Bethlehem, PA.
The reorganization was driven by the loss of exclusivity on Daiichi Sankyo's best-selling medication, Olmesartan/Benicar, which loses its patent protection in 2016. Benicar is used in the treatment of hypertension and was responsible for about 27 percent of annual revenue for the company. Last year the medication brought in $2.6 billion. Benicar is prescribed to keep blood vessels from narrowing, which lowers blood pressure and improves blood flow.
Leading up to 2015, Daiichi Sankyo bolstered its pipeline when it gained Phase III acute myeloid leukemia (AML) candidate quizartinib after acquiring Ambit Biosciences in a deal worth $410 million. Ambit is a biopharma company focused on the discovery and development of medicines to treat unmet medical needs in oncology, autoimmune and inflammatory diseases by inhibiting enzymes behind those diseases. Ambit's lead drug candidate, quizartinib, is targeted at patients with AML.
In another move, Japan-based Daiichi Sankyo's U.S. subsidiary merged with its U.S.-based sister company, Asubio Pharmaceuticals, which will be integrated into the Daiichi Sankyo global development organization.
Editor: Tim Wright
Associate Editor: Kristin Brooks
All profiles compiled by Tim Wright, except Gilead, Amgen, Boehringer-Ingelhaim and Biogen, by Kristin Brooks Pipeline/revenue information compiled by Kristin Brooks
* Profile information is sourced from each company's annual report along with press releases distributed throughout the year.
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|Article Type:||Cover story|
|Date:||Jul 1, 2016|
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