Top 25 pharma and biopharma report.
03 Merck & Co.
07 Johnson & Johnson
13 Eli Lilly & Co.
14 Bristol-Myers Squibb
16 Boehringer Ingelheim
17 Novo Nordisk
18 Merck KGaA
TOP 25 PHARMA AND BI0PHARMA COMPANIES (Based on 2016 Pharma/Biopharma Sales, in $U.S. Millions) 01. Pfizer $52,824 02. Novartis $48,518 03. Merck & Co. $39,807 04. Roche $38,369 05. GlaxoSmithKline $37,929 06. Sanofi $35,633 07. Johnson & Johnson $33,464 08. Gilead $30,390 09. AbbVie $25,638 10. AstraZeneca $23,002 11. Amgen $22,991 12. Teva $21,903 13. Eli Lilly & Co. $21,222 14. Bristol-Myers Squibb $19,427 15. Bayer $17,300 16. Boehringer Ingelheim $16,699 17. Novo Nordisk $15,841 18. Merck KGaA $15,828 19. Takeda $15,565 20. Allergan $14,570 21. Biogen $11,449 22. Shire $11,397 23. Celgene $11,229 24. Mylan $11,077 25. Otsuka $10,240
01 PFIZER, INC.
Headquarters: New York, NY
HEADCOUNT: 64,000 YEAR ESTABLISHED: 1849 REVENUES: $52,824 (+8%) NET INCOME: $7,215 (+4%) R&D: $7,872 (+2%) DRUGS APPROVED DRUG INDICATION Bavencio urothelial carcinoma Eucrisa mild to moderate atopic dermatitis Nimenrix meningococcal group A, C, W-135, and Y Xalkori ROS1-positive advanced non-small cell lung cancer Prevnar 13 pneumococcal pneumonia, adults 18 through 49 years DRUGS PENDING DRUG INDICATION Trumenba adolescent and young adult meningitis B tafamidis meglumine transthyretin familial amyloid polyneuropathy Bavencio 2nd line metastatic merkel cell carcinoma inotuzumab acute lymphoblastic leukemia ozogamicin ertugliflozin diabetes mellitus-type 2 PHASE IIB AND BEYOND DRUG INDICATION Bavencio (avelumab) non-small cell lung cancer, gastric cancer, ovarian cancer, kidney cancer, head and neck cancer Ertugliflozin type 2 diabetes Ibrance (palbociclib) high risk early breast cancer lorlatinib non-small cell lung cancer Prophylactic Vaccine clostridium difficile colitis Rivipansel vaso-occlusive crisis associated with sickle cell disease somatrogon adult growth hormone deficiency talazoparib breast cancer Tanezumab OA signs and symptoms, chronic low back pain, cancer pain Trumenba meningococcal serogroup B Vyndaqel cardiomyopathy Xeljanz ulcerative colitis, psoriatic arthritis Xtandi breast cancer, prostate cancer Coagulation Factor IX hemophilia Dekavil rheumatoid arthritis Dopamine 1 Parkinson's disease glasdegib acute myeloid leukemia JAK3 Inhibitor alopecia areata, rheumatoid arthritis, ulcer- ative colitis Myostatin Inhibitor Duchenne muscular dystrophy Prophylactic Vaccine staphylococcus aureus EARLY RESEARCH PROJECTS DRUG INDICATION PF-06342674 diabetes mellitus-type 1 PF-06423264 acne PF-06817024 atopic dermatitis PF-06823859 lupus PF-05221304 non-alcoholic steatohepatitis PF-06282999 acute coronary syndrome PF-06293620 diabetes mellitus-type 2 PF-06427878 hyperlipidemia PF-04958242 schizophrenia PF-05251749 Alzheimer's disease PF-06669571 cognitive disorder PF-06818883 intracerebral hemorrhage PF-04136309 pancreatic cancer PF-06647020 cancer PF-06747143 acute myeloid leukemia PF-06482077 bacterial infections DRUGS COMING OFF PATENT DRUG INDICATION YEAR Viagra erectile dysfunction 2017 Lyrica epilepsy, neuropathy 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Prevnar family pneumoccal vaccine $5,718 -8% Lyrica epilepsy, neuropathy $4,165 14% Enbrel rheumatoid arthritis $2,909 -13% Ibrance cancer $2,135 n/a Lipitor cholesterol $1,758 -6% Viagra erectile dysfunction $1,181 -9% Sutent cancer $1,095 -2% Premarin menopause $1,017 flat Norvasc hypertention $962 -3% Celebrex pain $733 -12%
Headquartered in New York City, Pfizer jumped past Novartis to reclaim its spot as the largest pharmaceutical company in the world by revenue. The company reported an 8% growth to $52.8 billion for 2016 as compared to $48.9 billion in 2015. Pfizer's portfolio includes medicines, vaccines, and consumer healthcare products separated into two businesses: Innovative Health and Essential Health.
The Innovative Health segment includes the global innovative pharmaceuticals segment and the global vaccines, oncology, and consumer healthcare segment and accounts for more than half of the company's total revenues. The revenue contribution from the segment rose to 55% of total revenues for 2016. The Innovative Health revenues increased 11% to $29.2 billion in 2016 primarily due to an increase in sales of Lyrica, Ibrance, Eliquis, Xeljanz, Xtandi, and the strong performance of new products.
Pfizer Essential Health, formerly known as the Global Established Pharma segment, is focused on non-viral anti-infectives, biosimilars and sterile injectable medicines. The Essential Health business also includes legacy Hospira products. In September 2015, Pfizer acquired Hospira to create a leading provider of global sterile injectables that now encompasses one of the broadest and most diverse portfolios of sterile injectable medicines in the industry. The Essential Health segment revenue's rose 11% to $23.6 billion in 2016, driven by increased sales of legacy Hospira products.
Many of Pfizer's R&D pipeline's new molecular entities are aimed at a range of cancers, including kidney, breast, prostate, lung and blood cancers, and include biologics, chemicals, immunotherapies, gene therapies and biosimilars.
In 2016, Pfizer achieved several regulatory milestones. Its breakthrough oncology product Ibrance, which was approved by the FDA in the U.S. in 2015 for the initial treatment of the most common form of advanced breast cancer, received a new U.S. indication for recurrent disease. Ibrance also was approved in 2016 by the European Medicines Agency (EMA) for both initial and recurrent disease. There are 77 ongoing or completed collaborative Ibrance studies with investigators, 43 of which are in breast cancer and 34 in non-breast tumors including pancreatic and head and neck cancers.
Xalkori, Pfizer's treatment for non-small cell lung cancer, was approved by the FDA for a certain type of lung cancer known as ROS-1.
Two therapies in development for cancer were accepted for regulatory review in 2016. Inotuzumab for acute lymphoblastic leukemia is now in registration in the EU, and avelumab for metastatic Merkel cell carcinoma is being reviewed in the U.S. and EU.
Together with its partner Merck KGaA, Pfizer is expanding its foothold in immuno-oncology where it currently has 30 avelumab clinical programs in the clinic and in 2016, launched four "first-in-patient" studies and now has eleven immunooncology entries in the clinic. Pfizer is now well positioned to capitalize on what many believe will be the future of cancer treatment--immuno-oncology agents combined with more conventional therapies.
DRIVING PROGRESS IN THE BIOSIMILARS MARKET
As the leading global biosimilars company, Pfizer currently has three marketed biosimilars as part of its acquisition of Hospira--Inflectra (infliximab-dyyb), Retacrit (epoetin zeta) and Nivestim (filgrastim)--available to patients in several markets. Inflectra, which is marketed under other brand names in some countries, is approved in more than 70 countries. Pfizer's robust biosimilars pipeline consists of eight distinct molecules in mid-to-late stage development, and six in early-stage development. Three of its late-stage pipeline products have reported positive top-line data from Phase III studies, and full data results are anticipated in 2017-2018.
Over the past year, the company has also worked to advance the U.S. biosimilars marketplace. In 2016, Pfizer launched Inflectra, a biosimilar for Remicade in the U.S. It marks the first monoclonal antibody (mAb) biosimilar to be both approved and launched in the U.S. It received FDA clearance in November 2016 and will treat difficult conditions including rheumatoid arthritis (RA), Crohn's disease, plaque psoriasis and ulcerative colitis (UC).
Pfizer's 14 biosimilars in the pipeline are expected to compete in a global market that may grow to $17-20 billion over the next five to 10 years. To offer support to patients and providers in the U.S., Pfizer launched the Pfizer enCompass Program, a comprehensive reimbursement and patient support program for biosimilars.
Pfizer is also developing new therapies for improving the quality of life of people who live with debilitating conditions such as RA, lupus, psoriatic arthritis and inflammatory bowel disease (IBD), including UC. It's expertise in Janus kinase inhibitors (JAK), which interfere with the inflammation process in autoimmune diseases, is enabling it to advance several other potential anti-inflammatory therapies beyond the marketed product Xeljanz. Pfizer anticipates initiating approximately six JAK studies in 2017.
In addition, Pfizer has a rich history in vaccine research and development, and in 2016 continued to improve and expand its portfolio of potentially life-saving vaccines. The European Commission approved an expanded indication for its Nimenrix vaccine making it the first and only conjugate vaccine in the EU for immunizing infants six weeks of age and older against invasive meningococcal disease caused by a certain group of bacteria. In addition, Pfizer's Meningococcal Group B (MenB) vaccine, Trumenba, was approved by the FDA for a new two-dose schedule designed to help prevent MenB in healthy adolescents and young adults. Pfizer also continued to advance its Staphylococcus aureus (S. aureus) and Clostridium difficile (C. difficile) vaccine candidates, designed to prevent widespread and increasingly drug-resistant infections.
COLLABORATIONS AND ACQUISITIONS
Collaboration is an important element of Pfizer's overall discovery and early development process. In 2016, it received breakthrough therapy designation from the FDA for a hemophilia gene therapy being developed in partnership with SPARK Therapeutics. It also acquired Bamboo Therapeutics, a privately held biotech based in Chapel Hill, NC, focused on developing gene therapies for the potential treatment of patients with certain rare diseases including Duchenne muscular dystrophy (DMD) and Friedreich's ataxia (FA). Through this acquisition Pfizer acquired a number of novel assets, key technology and manufacturing capabilities that position it to be ahead of the curve in this developing area of research that the company says has the potential to be game-changing.
In December 2016, Pfizer completed the acquisition of Astra-Zeneca PLC's small molecule anti-infective business, primarily outside the U.S., including the commercialization rights and development rights in certain markets to the newly approved EU drug Zavicefta (ceftazidime-avibactam), the marketed agents Merrem/Meronem (meropenem) and Zinforo (ceftaroline fosamil), and the clinical development assets aztreonam-avibactam (ATM-AVI) and ceftaroline-avibactam (CXL). Zavicefta specifically addresses certain multi-drug resistant Gram-negative infections, including those resistant to carbapenem antibiotics, one of the largest threats to global health in the field of infectious disease.
Pfizer also advanced its collaboration with Merck & Co. on ertugliflozin, which is in a new class of treatments for type 2-diabetes, the world's most prevalent type, and expects regulatory action in 2017. Through a partnership with Eli Lilly & Co., Pfizer has initiated six new Phase III trials to continue the development of tanezumab, a novel potential treatment option for chronic, debilitating pain in patients with osteoarthritis, lower back pain and cancer.
Pfizer also entered into several research collaborations and business relationships. They include collaborations with Biolnvent International AB to develop antibodies targeting tumor-associated myeloid cells and Western Oncolytics to advance their novel oncolytic vaccinia virus, WO-12, adding another novel technology platform to its cancer vaccine efforts, as well as a relationship with IBM where it will utilize IBM Watson for Drug Discovery to help accelerate research in immuno-oncology by identifying potential new targets and combination therapies.
Domain Therapeutics, a biopharma company specializing in new drug candidates that target G protein-coupled receptors (GPCRs), entered a collaboration agreement with Pfizer to assess the impact of mutations on different signaling pathways engaged by GPCRs. Domain will use its bioSensAll technology to define signaling signatures for each of the wild-type and mutant receptors. The bioSensAll technology allows for easier understanding of signaling pathways activated by each candidate molecule, predicting its pharmacological profile. This makes it possible to choose at an early stage molecules that have the required activity but do not present side effects or induce tolerance to treatment. The collaboration aims to validate potential targets across a range of therapeutic indications.
Pfizer also entered a new therapeutic antibody discovery collaboration with AbCellera Biologies to apply its mAb screening platform to discover function-modulating antibodies against undisclosed membrane protein targets. AbCellera's platform allows it to screen natural immune repertoires with unparalleled depth to unlock challenging discovery programs.
Lastly, Pfizer gained an eczema asset when it paid $5.2 billion for Anacor Pharmaceuticals. The company's lead asset, crisaborole, is a non-steroidal topical PDE4 inhibitor with antiinflammatory properties for the treatment of mild-to-moderate atopic dermatitis, or eczema. In two Phase III studies, crisaborole achieved statistically significant results on all primary and secondary endpoints. Pfizer received FDA approval at the end of the year and said it believes peak sales for crisaborole could potentially reach $2.0 billion annually.
PFIZER BREAKS GROUND ON NEW BIOLOGICS FACILITY
Clinical manufacturing facility will support Pfizer's diverse biologics research efforts
During the year, Pfizer broke ground on its new biologics clinical manufacturing facility in Andover, MA, and will invest more than $200 million to enable the production of complex biologics and vaccines. The new five-story building is expected to be operational by January 2019.
The Andover campus currently includes seven buildings, which house laboratories, clinical and commercial manufacturing suites, and support areas. It also includes a multiproduct manufacturing facility, which allows clinical and commercial products to be manufactured simultaneously.
The new clinical manufacturing facility is designed with five independent manufacturing suites to support Pfizer's complex and diverse biologics research efforts. The facility will employ flexible design to enable next generation manufacturing strategies and will leverage single-use bioreactors and disposable process technologies.
Headquarters: Basel, Switzerland
HEADCOUNT: 118,000 YEAR ESTABLISHED: 1996 REVENUES: $48,518 (-2%) PHARMA REVENUES: $32,562 (-2%) NET INCOME: $11,314 (-6%) R&D: $9,039 (+1%) DRUGS APPROVED DRUG INDICATION Lucentis choroidal neovascularization in rare diseases Arzerra chronic lymphocytic leukemia Maris periodic fever syndromes Kisqali Femara HR+/HER2- postmenopausal advanced Co-Pack breast cancer Rydapt acute myeloid leukemia Zykadia ALK+ advanced NSCLC Ribociclib 1st line HR+/HER2- advanced breast cancer DRUGS PENDING DRUG INDICATION AfinitorA/otubia TSC seizures Revolade aplastic anemia Signifor LAR Cushing's disease Tafinlar + Mekinist BRAF V600+ non-small cell lung cancer Tasigna CML treatment-free remission PHASE IIB AND BEYOND DRUG INDICATION ACZ885 secondary prevention of cardiovascular (canakinumab) events ACZ885 (canakinumab) migraine Arzerra non-Hodgkin's lymphoma BAF312 secondary progressive multiple sclerosis BYL719 + fulvestrant HR+/HER2- postmenopausal aBC 2nd line CAD106 Alzheimer's disease Cosentyx non-radiographic axial spondyloarthritis Entresto chronic heart failure with preserved ejection fraction, post-acute myocardial infarction FTY720 (fingolimod) pediatric multiple sclerosis Jakavi graft-versus-host disease, early myelofibrosis LAM320 multi-drug resistant tuberculosis LCI699 Cushing's disease Lucentis retinopathy of prematurity 0MB157 (otatumumab) relapsing multiple sclerosis PKC412 acute myeloid leukemia Promacta / Revolade severe aplastic anemia QAW039 asthma RTH258 nAMD, diabetic macular edema RLX030 (serelaxin) acute heart failure SEG101 sickle cell disease EARLY RESEARCH PROJECTS DRUG INDICATION ABL001 chronic myeloid leukemia PIM447 hematologic tumors GP2018 autoimmune diseases DRUGS COMING OFF PATENT DRUG INDICATION YEAR Gleevec oncology 2018 Gilenya autoimmune disease 2017 Exjade iron chelation 2017 Starlix blood glucose lowering agent 2017 Lotrel cardiovascular disorders 2017 Exforge hypertension 2017 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Gleevec/Glivec oncology $3,323 -29% Gilenya autoimmune disease $3,109 12% Lucentis age-related macular $1,835 -11% degeneration Tasigna chronic myeloid leukemia $1,739 7% Sandostatin acromegaly $1,646 1% Afinitor oncology $1,516 -6% Cosentyx Psoriasis, ankylosing $1,128 nm spondylitis and psoriatic arthritis Galvus diabetes $1,193 5% Diovan hypertension $1,073 -16% Exjade chronic iron overload $956 4%
Novartis slipped to number two with flat revenues in 2016 compared to 2015. However, at $48.5 billion the Basel, Switzerland-based drug maker is still a Big Pharma giant.
The major drivers behind the company's falling revenues have included adjustments for changes to its businesses, including its acquisition of GlaxoSmithKline's (GSK) Oncology business and its divestiture of its Vaccines and Consumer Healthcare divisions to GSK in March 2015.
Novartis started divesting its business segments in 2014. Its Animal Health business was divested to Eli Lilly, while it divested parts of its Vaccines business and its Consumer Healthcare business to GSK. It also divested its Influenza Vaccines business to CSL Group. It acquired GSK's oncology business in March 2015.
To reflect these changes and the importance of oncology to the company following the integration of the oncology assets acquired from GSK, during the year Novartis restructured its Pharmaceuticals Division by creating two business units--Novartis Pharmaceuticals and Novartis Oncology. Both units form the Innovative Medicines Division and consists of products for therapeutic areas including oncology, cardio-metabolic, immunology and dermatology, retinal, respiratory, neuroscience, and established medicines. The Innovative Medicines segment reported a fall of 2% to $32.6 billion in 2016, representing 67% of total company revenue.
Sandoz is Novartis' generics and biosimilars division, which includes the retail generics, anti-infectives and biopharmaceuticals franchises. It is the number two generic medicines provider worldwide, and it's number one in differentiated generics, including products that are difficult to develop and manufacture. In 2016, Sandoz contributed nearly 30% of total revenue at $10.14 billion, marking a 2% increase over the previous year. Alcon, the company's eye care unit, makes up the remaining $5.76 billion of 2016 revenue.
UPPING BIOSIMILAR STAKES
Sandoz's revenue drivers are biopharmaceuticals, including biosimilars and Glatopa. The segment's growth was reported across all regions worldwide. In U.S. markets, its reported revenue for 2016 was $3.7 billion, a 1% rise. European markets reported a 7% rise in revenue to $4.4 billion, driven by strong sales in the region. Canadian and Latin American markets reported a rise of 9% during the year.
The global sales of biopharmaceuticals rose 31% to $1 billion in 2016. These sales included revenue from biosimilars, biopharmaceutical contract manufacturing, and Glatopa. The growth came mainly from the three in-market biosimilars--Omnitrope (somatropin), Binocrit (epoetin alfa), and Zarzio/Zarxio (filgrastim)--along with the strong performance of Glatopa in U.S. markets.
Glatopa (glatiramer acetate) injection is the first generic version of Teva Pharmaceutical's Copaxone 20mg used for the treatment of relapsing forms of multiple sclerosis. The segment's anti-infective franchise reported a fall of 2% in revenue at a constant exchange rate at $1.4 billion in 2016.
Also on the biosimilar front, Sandoz during the year acquired from Pfizer the rights for the development and commercialization of PF-06438179 (biosimilar infliximab) in the 28 countries that form the European Economic Area (EEA). Infliximab is a tumor necrosis factor alpha (TNF-alpha) inhibitor used to treat a range of autoimmune diseases including rheumatoid arthritis (RA) and psoriasis.
Sandoz also advanced its biosimilars program with EMA acceptance of regulatory submission for its biosimilar to Amgen's EU-licensed Neulasta (pegfilgrastim)--a long-acting recombinant human granulocyte colony-stimulating factor (G-CSF). Sandoz is seeking approval for the same indication as the reference product.
Novartis and Bristol-Myers Squibb (BMS) entered into a clinical research collaboration to investigate the safety, tolerability, and efficacy of Mekinist (trametinib) in combination with Opdivo (nivolumab) and Opdivo + Yervoy (ipilimumab) regimen as a potential treatment option for metastatic colorectal cancer. BMS will conduct the study, which is expected to establish recommended dose regimens and the preliminary anti-tumor activity of the combination therapies. Both companies will evaluate the results to determine optimal approaches and potential clinical development of these combinations.
Allergan entered into a clinical trial agreement with Novartis to conduct a Phase lib study, using Allergan's cenicriviroc (CVC) and Novartis'lead FXR agonist for the treatment of non-alcoholic steatohepatitis (NASH). The study will assess the safety, efficacy and tolerability of this multi-therapy treatment approach for NASH. CVC is a once-daily, oral, Phase III ready potent immunomodulator that blocks two chemokine receptors, CCR2 and CCR5, which are involved in inflammatory and fibrogenic pathways.
Novartis is developing Farnesoid X receptor (FXR) agonists for the treatment of chronic liver diseases, including NASH. The most advanced investigational compound is a potent, non-bile acid FXR agonist, which recently received Fast Track designation from the FDA and is in a Phase II clinical trial. As part of this agreement, Novartis and Allergan will conduct a Phase lib clinical trial to assess the safety, efficacy and tolerability of a multitherapy treatment for NASH.
Novartis also entered a $225 million cardiovascular deal with Ionis Pharmaceuticals to develop and commercialize AKCEAAPO(a)-L Rx and AKCEA-APOCIII-L Rx, novel potential therapies to treat cardiovascular disease. The partnership allows the companies to move more rapidly to Phase III cardiovascular outcomes studies. Ionis and its subsidiary Akcea plan to conduct a Phase II dose-ranging study for each drug, to choose the optimal dose and evaluate alternative dose schedules, such as monthly dosing, for the Phase III study. Following the successful completion of each Phase II dose-ranging study, and prior to initiation of the Phase III study, Novartis will be able to exercise its option to license and commercialize each drug.
BOLSTERING THE IMMUNO-ONCOLOGY PIPELINE
At the start of 2015 Novartis launched a new immuno-oncology research team led by cancer vaccine pioneer Glenn Dranoff. In a short period of time, the team built a broad portfolio of clinical and pre-clinical programs focused on stimulating the body's immune system to combat cancers through targeting critical regulatory steps in the anti-tumor immune response.
Today the company's immuno-oncology portfolio includes novel checkpoint inhibitors, chimeric antigen receptor T-cell (CART) technology, myeloid cell targeting agents, the T-cell stimulating factor IL-15, STING agonists that enhance immune recognition of cancers, and adenosine receptor antagonists and TGF-beta blocking antibodies that overcome immunosuppression in the tumor microenvironment.
During the year, Novartis made a series of acquisitions and strategic collaborations between itself and biotech companies that have helped bolster its immuno-oncology pipeline. It continued to grow the pipeline through a collaboration and licensing agreement with Surface Oncology that gave Novartis access to four preclinical programs that target regulatoryT cell populations, inhibitory cytokines, and immunosuppressive metabolites in the tumor microenvironment.
Novartis also added bispecific antibodies to its immuno-oncology portfolio through a collaboration and licensing agreement with Xencor. Traditional monoclonal antibodies target and bind to a single antigen. Bispecific antibodies are engineered to recognize and target two different antigens, which makes them potentially more effective in targeting complex diseases. A T-cell engaging bispecific antibody is able to bind an antigen on a tumor cell with one arm and engage T-cells capable of their destruction with the other.
Novartis has the right to develop four additional bispecific antibodies and to use other Xencor proprietary antibody engineering technology for up to ten additional biotherapeutic programs across the Novartis R&D portfolio. In addition, the companies will collaborate to co-develop Xencor's two bispecific T-cell engaging antibodies targeting CD3xCD123 and CD3xCD20 for the treatment of acute myeloid leukemia and B-cell malignancies.
Novartis also signed an exclusive option, collaboration and license agreement with Conatus Pharmaceuticals, a biotech focused on the development of novel medicines to treat liver disease. This agreement enables Novartis and Conatus to jointly develop emricasan, an investigational, first-in-class, oral, pancaspase inhibitor for the treatment of NASH with advanced fibrosis (scarring) and cirrhosis. This collaboration has the potential to expand treatment options for people in various stages of fatty liver disease, where no approved medicines currently exist.
In terms of new drug approvals, two of Novartis' drugs for which regulatory decisions are expected soon include LEE011, an investigational drug in combination with letrozole for the treatment of HR+/HER2- advanced breast cancer, and PKC412, an investigational drug for the treatment of acute myeloid leukemia. Both drugs have been granted priority review designations by the FDA. Other regulatory decisions are expected for biosimilars.
Novartis is also going to submit new drug applications for CTL019, an investigational drug for the treatment of acute lymphoblastic leukemia in children, and AMG334, an investigational drug for the treatment of migraines, developed in partnership with Amgen.
During the year Novartis' Cosentyx (secukinumab) was approved by the FDA for two new indications, active ankylosing spondylitis (AS) and active psoriatic arthritis (PsA). Both are life-long, painful and debilitating inflammatory diseases that affect the joints and/or spine. Cosentyx is now the first and only interleukin-17A (IL-17A) antagonist approved for AS, as well as moderate to severe plaque psoriasis and PsA, which impacts as many as 30% of patients with psoriasis.
NOVARTIS BUYS BLOOD DISEASE DRUG MAKER FOR $665M
Purchase of Selexys complements and broadens hematology pipeline
Novartis acquired Selexys Pharmaceuticals, a drug maker specializing in development of therapeutics in certain hematologic and inflammatory disorders. Novartis exercised its right to acquire Selexys following receipt of results of the SUSTAIN study, a Phase II trial evaluating the use of SelG1, an anti-P-selectin antibody, in the reduction of vaso-occlusive pain crises in patients with sickle cell disease (SCD).
Novartis obtained the exclusive right to acquire Selexys and SelG1 in 2012, Prior to the acquisition, Selexys Pharmaceutical Corporation was a privately held biopharmaceutical company headquartered in Oklahoma City, Oklahoma. Terms of the deal could total up to $665 million in upfront, acquisition and milestone payments.
"Sickle cell disease affects millions of people around the world and there are limited therapies available for treatment of vaso-occlusive pain crises, a very common complication of the disease," said Bruno Strigini, chief executive officer, Novartis Oncology. "With this acquisition, Novartis is able to leverage its leadership in hematology research to advance development of a potential new treatment option for patients living with this debilitating condition."
"We would like to extend our gratitude to all of the dedicated patients, physicians and nurses who participated in the SUSTAIN study of SelG1 in sickle cell disease," said Dr. Scott Rollins, former president and chief executive officer, Selexys Pharmaceuticals. "Further, the acquisition of Selexys by Novartis represents an important step in the continued development of SelG1, a novel, potential first-in-class therapy for patients with this underserved life-threatening disease."
TOP 25 COMPANIES
Headquarters: Whitehouse Station, NJ
HEADCOUNT: 68,000 YEAR ESTABLISHED: 1889 REVENUES: $39,807 (+1%) PHARMA REVENUES: $35,151 (+1%) NET INCOME: $5,712 (+28%) R&D: $7,194 (+7%) DRUGS APPROVED DRUG INDICATION Keytruda Mismatch Repair Deficient Cancer, bladder cancer, classical Hodgkin lymphoma, non-small cell lung cancer, head and neck cancer Zinplava Clostridium difficile infection DRUGS PENDING DRUG INDICATION MK-8237 Allergy, House Dust Mite MK-8835B Diabetes Mellitus MK-1293 Diabetes Mellitus V419 Pediatric Hexavalent Combination Vaccine PHASE IIB AND BEYOND DRUG INDICATION verubecestat Alzheimer's disease anacetrapib atherosclerosis Relebactam bacterial infection Keytruda breast cancer, Esophageal cancer, Hodg- kin Lymphoma, liver cancer, colorectal cancer letermovir CMV prophylaxis in transplant patients V920 ebola vaccine Sivextro bacterial pneumonia vericiguat heart failure doravirine HIV MK-1029 asthma MK-1029 cancer MK-7264 cough, including cough with Idiopathic Pulmonary Fibrosis MK-5172 hepatitis C V114 pneumoconjugate vaccine EARLY RESEARCH PROJECTS DRUG INDICATION Pembrolizumab breast cancer M7824 solid tumors MK5160 type 1 diabetes mellitus MK3475 multiple myeloma MK8591 HIV DRUGS COMING OFF PATENT DRUG INDICATION YEAR RotaTeq rotavirus 2019 Noxafil antifungal 2019 Emend for injection chemotherapy induced 2019 nausea and vomiting TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Januvia/Janumet diabetes, obesity $6,109 2% ZetiaA/ytorin cholesterol $3,701 -2% Gardasil HPV vaccine $2,173 14% Remicade rheumatoid arthritis $1,268 -29% Keytruda cancer $1,402 148% Isentress HIV/AIDS $1,387 -8% Proquad, MMR, vaccines $1,640 9% and Varivax Cubicin antibiotic $1,087 -4% Singular asthma $915 -2% Pneumovax 23 vaccines $641 18%
Headquartered in Whitehouse Station, NJ, Merck climbed a spot to number three with 2016 revenue of $39.8 billion. The company operates in over 100 countries, and 55% of its total revenue comes from sales outside U.S. markets. The global human health segment, or pharmaceuticals, is the highest revenue-generating segment at the company and contributed nearly 88% of total revenues. This segment includes various franchises like oncology, vaccines, hospital acute care, diabetes, and women's health.
BLOCKBUSTERS LEAD THE WAY
Merck's pharmaceuticals segment has several blockbuster drugs with a yearly contribution of over $1 billion each. Keytruda is part of Merck's immuno-oncology franchise and used to treat non-small cell lung cancer as well as melanoma, a type of skin cancer. Merck launched Keytruda in the fourth quarter of 2014. Last year it Keytruda's global sales were $1.4 billion, a nearly 150% growth in revenues as compared to $566 million in 2015.
Januvia and Janumet are two of Merck's blockbuster drugs in the diabetes franchise. These drugs are used to lower blood sugar levels in patients with type two diabetes and combined sales for these drugs were $6 billion.
Remicade, a top-selling drug for the treatment of inflammatory disorders, is losing its market share due to the entry of generic competitors and biosimilars following the loss of exclusivity in European markets. Revenues fell 29% to $1.3 billion.
Simponi is another drug in the immunology franchise that saw revenues rise 11% to $766 million while the combined revenues of cardiovascular drugs Zetia and Vytorin fell to $3.7 billion due to the loss of exclusivity of Vytorin in the U.S.
The Gardasil franchise is Merck's leading vaccines franchise for the prevention of certain strains of human papillomavirus (HPV). Total sales of the Gardasil franchise in 2016 were $2.2 billion, an increase of 14%.
Merck entered a $280 million cancer collaboration with Complix, a biopharmaceutical company developing a pipeline of protein therapeutics called alphabodies for the treatment of cancer and severe autoimmune diseases. The strategic drug discovery collaboration through Merck's subsidiary, Merck Sharp & Dohme Corp. (MSD), will focus on developing cell-penetrating alphabodies (CPABs) for the treatment of cancer. Complix will use its proprietary Alphabody platform to deliver CPABs against up to two intracellular cancer targets. MSD will fund related research activities and has an option to the exclusive, worldwide rights for any of the resulting compounds.
Adimab entered into an agreement with Merck to transfer its antibody technology to Merck Research Labs for the discovery and optimization of monoclonal and bispecific therapeutic antibody candidates. This technology transfer expands an ongoing collaboration initiated in 2009 that has resulted in several undisclosed therapeutic candidates for Merck. Adimab will transfer and license its antibody discovery and optimization platform to Merck. Merck will receive a custom human antibody library and will obtain a license to the Adimab platform for use in all therapeutic areas and targets. Merck has also secured an option to receive continued improvements to the Adimab platform, including access to new antibody libraries.
AbCellera has entered a collaboration with Merck to generate antibodies against an undisclosed disease target. AbCellera will apply its high-throughput antibody discovery platform to identify antibodies that specifically modulate target function. Merck has the option to develop antibody candidates identified through the collaboration for specified therapeutic applications.
In another cancer pact, ImmunoGen and Merck joined forces to evaluate an ovarian cancer drug combo. The clinical research collaboration was set up to assess ImmunoGen's mirvetuximab soravtansine in combination with Merck's anti-PD-1 therapy, Keytruda (pembrolizumab), for the treatment of patients with FRa-positive ovarian cancer. ImmunoGen is conducting a Phase Ib/II trial evaluating mirvetuximab soravtansine for FR[alpha]-positive ovarian cancer used in combination with other anticancer agents. The assessment of mirvetuximab soravtansine with Keytruda will be added to this trial, with Merck supplying the Keytruda. The agreement may be expanded to include a subsequent Phase III clinical trial.
Merck and Moderna Therapeutics formed a $200 million strategic collaboration and license agreement to develop and commercialize novel messenger RNA (mRNA)-based personalized cancer vaccines. The collaboration will combine Merck's established leadership in immuno-oncology with Moderna's pioneering mRNA vaccine technology and GMP manufacturing capabilities to advance individually tailored cancer vaccines for patients across a spectrum of cancers.
Moderna and Merck will develop personalized cancer vaccines that utilize Moderna's mRNA vaccine technology to encode a patient's specific neoantigens, unique mutations present in that specific patient's tumor. When injected into a patient, the vaccine will be designed to elicit a specific immune response that will recognize and destroy cancer cells. The companies believe that the mRNA-based personalized cancer vaccines' ability to specifically activate an individual patient's immune system has the potential to be synergistic with checkpoint inhibitor therapies, including Merck's anti-PD-1 therapy, Keytruda (pembrolizumab). In addition, Moderna has developed a rapid cycle time, small-batch manufacturing technique that will uniquely allow the company to supply vaccines tailored to individual patients within weeks.
The development program will entail multiple studies in several types of cancer and include the evaluation of mRNA-based personalized cancer vaccines in combination with Merck's Keytruda (pembrolizumab). Moderna will also utilize the upfront payment to fund a portion of the build-out of a GMP manufacturing facility in suburban Boston for the purpose of personalized cancer vaccine manufacturing.
In June 2016 Merck bought the clinical-stage biotech Afferent Pharmaceuticals in a deal worth up to $1.25 billion. The move gave Merck access to Afferent's lead investigational candidate AF-219 for chronic cough treatment. Merck purchased all outstanding shares of Afferent for an upfront fee of $500 million, and could pay an extra $750 million linked to certain clinical development and commercial milestones.
AF-219 is a selective, non-narcotic, orally-administered P2X3 antagonist currently being evaluated in a Phase lib clinical trial for the treatment of refractory, chronic cough, as well as in a Phase II clinical trial in idiopathic pulmonary fibrosis (IPF) with cough.
P2X3 receptors are believed to play a key role in the sensitization of certain sensory nerves, which become activated under pathological conditions mediated by a common cellular signal, ATP, when it is released in high concentrations due to cellular distress following injury or infection. Afferent's compounds are designed to selectively block ATP activation of P2X3 channels, potentially reducing a range of sensory signs and symptoms.
Merck also acquired IOmet Pharma, bolstering its preclinical immuno-oncology pipeline. The UK-based drug discovery company is focused on cancer immunotherapy and cancer metabolism. Merck gained its preclinical pipeline of IDO (indoleamine-2,3-dioxygenase 1), TDO (tryptophan-2,3-dioxygenase), and dual-acting IDO/TDO inhibitors. IOmet became a wholly owned subsidiary of Merck.
Also of note, in March 2016, after 20 years, Merck and Sanofi Pasteur ended their joint vaccines operations in Europe. After concluding their joint venture, both companies said the plan was to integrate their respective European vaccine businesses into their operations, independently manage their product portfolios and pursue separate growth strategies in Europe.
The joint venture Sanofi Pasteur MSD, owned on a 50/50 basis, was created in 1994 to develop and commercialize vaccines from both companies' pipelines in 19 European countries. Numerous vaccines from Sanofi and MSD's development pipelines were launched, addressing key unmet medical needs. While the joint venture was successful over the past two decades from a public health and commercial perspective, the companies said that after considering their individual strategic priorities, alongside the economic and regulatory environments for vaccine operations in the EU, it was best to manage their respective vaccine product portfolios independently.
MERCK, FUJIFILM PARTNER ON $60M MICROBIAL BIOLOGICS FACILITY
New 20,000-liter facility to be used by Fujifilm for its contract development and
During the year Merck formed a long-term collaboration with Fujifilm Diosynth Biotechnologies, a global biologics contract development and manufacturing organization (CDMO), to invest in and operate a new 20,000 liter large-scale microbialbiologics facility for supply of active pharmaceutical ingredient (API) to its customers.
This collaboration involves a $60 million investment by Merck at its Brinny manufacturing plant in Innishannon, County Cork, Ireland. Merck in Brinny has been in operation for more than 30 years and is an integrated site for the development, testing and manufacturing of biologics.
It is intended that the large-scale biologics operations at Merck in Brinny will be operational in early 2018 for biotech and pharma customers of Fujifilm Diosynth.
The deal addresses a market need for large-scale microbial biologics manufacturing and complements Fujifilm Diosynth's existing microbial capacity that ranges from 100L up to 5000L both in the U.S. and UK.
According to the company, microbial fermentation remains vital technology for the process of manufacturing biologics, and this investment, drawing on the latest production advances, will enable Fujifilm Diosynth's existing and future customers to have a clear and secure line-of-sight to higher product volumes along with lower cost-of-goods. The latter is particularly important as products enter late clinical phase and commercialization.
Headquarters: Basel, Switzerland
HEADCOUNT: 94,052 YEAR ESTABLISHED: 1896 TOTAL REVENUES: $49,626 (+5%) PHARMA REVENUES: $38,369 (+5%) NET INCOME: $9,550 (+8%) R&D: $9,729 (+6%) DRUGS APPROVED DRUG INDICATION Actemra/RoActemra giant cell arteritis Lucentis diabetic retinopathy Tecentriq metastatic urothelial bladder cancer, meta-static non-small cell lung cancer Ocrevus primary progressK/e forms of multiple sclerosis Alecensa ALK-positive advanced non-small cell lung cancer DRUGS PENDING DRUG INDICATION Avastin glioblastoma multiforme, relapsed ovarian cancer, platinum-sensitive Gazyva front-line indolent non-Hodgkin's lymphoma atezolizumab metastatic non-small cell lung cancer, 2nd/3rd-line Alecensa ALK-positive non-small cell lung cancer, first-line treatment Actemra large-vessel vasculitis ocrelizumab relapsing multiple sclerosis PHASE IIB AND BEYOND DRUG INDICATION RG1273 pertuzumab advanced HER2-positive gastric cancer, early HER2-positive breast cancer RG7204 vemurafenib adjuvant melanoma, BRAF mutation positive RG7388 idasanutlin acute myeloid leukemia RG7421 cobimetinib BRAFv600 mutation-positive advanced + atezolizumab + melanoma, first-line treatment vemurafenib RG7446 atezolizumab ovarian cancer, front-line treatment, castration-resistant prostate cancer, extensive-stage small-cell lung cancer, first-line treatment, metastatic triple-negative breast cancer RG7446 + chemo +/- first-line non-squamous non-small cell lung Avastin atezolizumab cancer RG7446+ renal cell cancer Avastinatezolizumab RG7601 venetoclax relapsed or refractory multiple myeloma, acute myelogenous leukemia RG7413 etrolizumab ulcerative colitis, Crohn's disease RG1450 gantenerumab Alzheimer's disease RG6168 neuromyelitis optica RG7412 crenezumab Alzheimer's disease RG6013 emicizumab hemophilia A, patients without FVIII inhibitors RG1569 tocilizumab systemic sclerosis EARLY RESEARCH PROJECTS DRUG INDICATION RG7935 Parkinson's disease RG7906 psychiatric disorders RG7203 schizophrenia RG6100 Alzheimer's disease RG6029 pain RG6000 amyotrophic lateral sclerosis RG7992 metabolic diseases RG6080 nacubactam bacterial infections RG7880 inflammatory diseases RG7907 hepatitis B infection RG7861 infections caused by Staphylococcus aureus RG7990 asthma RG6069 fibrosis RG7888 solid tumors RG7446 atezolizumab HER2-positive breast cancer RG6185 oncology RG6069 fibrosis RG7986 relapsed or refractory B cell non-Hodgkin's lymphoma RG7882 ovarian cancer, pancreatic cancer RG7828 hematologic tumours RG7741 solid tumors or lymphoma DRUGS COMING OFF PATENT DRUG INDICATION YEAR Tarceva lung cancer 2018 Lucentis macular degeneration 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) MabThera/ rheumatoid arthritis $7,163 1% Rituxan Avastin breast cancer $6,656 -1% Herceptin cancer $6,656 1% Perjeta breast cancer $1,811 24% Actemra/ rheumatoid arthritis $1,665 15% RoActemra Xolair asthma $1,470 14% Lucentis macular degeneraton $1,380 -10% Activase/TNKase acute myocardial infarction $1,087 15% Tarceva lung cancer $1,005 -16% Kadcyla breast cancer $815 5%
Roche is a pioneer and leader in biologics for oncology and beyond and with $38.4 billion in drug sales for 2016, it moved up a spot from last year to become the fourth largest drug maker in the world. Sales in Roche's Pharmaceuticals Division were driven by strong growth of Perjeta, Herceptin and Actemra/RoActemra, while lower sales were recorded for Pegasys, Tarceva and Lucentis.
In the U.S., Pharmaceuticals sales advanced 3%, led by the respiratory medicines Xolair and Esbriet. The recently launched medicines Tecentriq and Alecensa contributed to the growth as well. Sales of eye drug Lucentis and cancer medicines Avastin and Tarceva declined due to growing use of other therapeutic options. In Europe, sales growth of 4% was driven by Perjeta, Actemra/RoActemra and MabThera/Rituxan.
Roche recently launched four new medicines: Cotellic (advanced melanoma), Alecensa (lung cancer), Venclexta (chronic lymphocytic leukemia) and Tecentriq (bladder and lung cancer). In addition, five FDA breakthrough therapy designations were granted for Roche medicines in 2016.
A major highlight was the U.S. launch of Roche's cancer immunotherapy medicine Tecentriq. It is the first FDA-approved treatment for people with a specific type of bladder cancer in more than 30 years. In addition, the FDA cleared Tecentriq for use in previously treated metastatic non-small cell lung cancer (NSCLC). The pivotal Oak trial showed that people with this form of lung cancer who received Tecentriq live significantly longer, regardless of their PDL1 status, compared with those receiving chemotherapy.
Additional data presented at the ECTRIMS4 congress in September showed that Roche's ocrelizumab increased disease control in both relapsing and primary progressive multiple sclerosis (RMS and PPMS). In March, Roche received regulatory approval for this medicine in RMS and PPMS in the U.S. and the EU.
Roche also presented other important clinical results in 2016. A pivotal study in a group of people with haemophilia A (Haven 1) showed that prophylaxis with emicizumab led to a significant reduction in the number of bleeds over time. A phase III study by Chugai (J-Alex) found that first-line treatment with Alecensa significantly reduced the risk of disease worsening or death compared to crizotinib, the current standard of care, in people with ALK-positive NSCLC. While Gazyva/Gazyvaro showed positive results in a major clinical trial (Gallium) in follicular lymphoma, a separate trial (Goya) of the medicine in diffuse large B-cell lymphoma, did not reach its primary study goal.
Also on the cancer battlefront, during the year, Roche launched the global cancer immunotherapy Centers of Research Excellence (imCORE) Network. This network brings together many of the world's leading scientific and clinical experts in cancer immunotherapy to collaborate in investigating the most promising new treatment approaches. The goal is to rapidly initiate preclinical and clinical research based on the latest scientific discoveries and to aggregate and share data to accelerate the search for cures for people with cancer. The imCORE Network will focus on identifying approaches to expand the number of people who benefit from cancer immunotherapy by exploring new ways to activate a person's immune system to fight their cancer.
Roche will invest up to roughly $100 million to support basic and clinical research collaborations related to cancer immunotherapy. This investment is incremental to Roche's on-going research and development of investigational medicines and treatment approaches in the field of cancer immunotherapy.
To further bolster its research efforts, Roche entered a collaboration with Catalent, through its subsidiary Redwood Bioscience, to develop next-generation molecules coupling different therapeutic modalities using Catalent's proprietary SMARTag 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 up-front 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.
RESTRUCTURING SMALL MOLECULES NETWORK
At the end of 2015, Roche unveiled plans to restructure its small molecules manufacturing network. The plans called for the closure of four manufacturing sites in Clarecastle, Ireland; Leganes, Spain; Segrate, Italy; and Florence, SC, in the U.S. The decision was made to address current underutilization as a result of its evolving portfolio.
The transition began in 2016 and is planned to end by 2021. During the year, Roche divested two of the facilities. The 300,000 sq.-ft. API manufacturing plant in Florence was sold to Patheon. At the time of the sale Roche entered into a multi-year supply arrangement with the contract development and manufacturing organization (CDMO).
The Spanish facility in Leganes was sold to the contract manufacturing organization (CMO) Famar. In addition, the two companies at the time of sale signed a long-term manufacturing agreement that will allow Famar Leganes to supply Roche in the future from this facility with the current portfolio of products produced at the site.
With these changes Roche is responding to the evolution of its small molecule portfolio towards specialized medicines produced in lower volumes. To support the manufacture of a new generation of specialized small molecule medicines--produced in lower volumes than traditional medicines--Roche is investing roughly $310 million in a dedicated facility in Kaiseraugst, Switzerland to provide future technology requirements.
Headquarters: Brentford, Middlesex, UK
HEADCOUNT: 99,300 YEAR ESTABLISHED: 2000 REVENUES: $37,929 (+7%) NET INCOME: $1,240 (-98%) R&D: $4,934 (-6%) DRUGS APPROVED DRUG INDICATION Relvar Ellipta COPD FluLaval flu vaccine Quadrivalent DRUGS PENDING DRUG INDICATION fluticasone furoate COPD + vilanterol + rheumatoid arthritis umeclidinium sirukumab Benlysta systemic lupus erythematosus Shingrix herpes zoster prophylaxis PHASE IIB AND BEYOND DRUG INDICATION dolutegravir + lamivudine HIV infections cabotegravir HIV pre-exposure prophylaxis tafenoquine Plasmodium vivax malaria Relenza influenza mepolizumab COPD fluticasone asthma furoate + vilanterol+ umeclidinium sirukumab giant cell arteritis 2998728 transthyretin-mediated amyloidosis 2696274 metachromatic leukodystrophy 2696275 Wiscott-Aldrich syndrome mepolizumab eosinophilic granulomatosis with polyangiitis retosiban spontaneous pre-term labour daprodustat anaemia associated with chronic renal disease EARLY RESEARCH PROJECTS DRUG INDICATION 3342830 bacterial infection 2838232 HIV infections 3228836 hepatitis B 3772847 severe asthma 2586881 pulmonary arterial hypertension 2269557 bronchietasis 3008348 idiopathic pulmonary fibrosis 3174998 solid tumours and haematological malignancies 2857916 multiple myeloma 3326595 cancer 2330811 systemic sclerosis 2646264 chronic urticaria 2618960 Sjogren's syndrome 2831781 autoimmune disease 3050002 psoriatic arthritis 3179106 inflammatory disorders of the bowel daprodustat wound healing 3008356 nonalcoholic steatohepatitis 2881078 muscle wasting mepolizumab severe atopic dermatitis DRUGS COMING OFF PATENT DRUG INDICATION YEAR Lexiva HIV 2018 Kivexa HIV 2019 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Seretide/Advair asthma, COPD $4,068 -28% Triumeq HIV $2,025 105% Tivicay HIV $1,112 39% Infanrix, Pediarix pediatric vaccine $898 -20% Ventolin asthma $916 -3% Flixotide/Flovent respiratory $743 -22% Avodart enlarged prostate $741 -26% Lamictal anti-epileptic $717 -12% Epzicom/Kivexa HIV $663 -38% Augmentin antibacterial $657 -19%
GlaxoSmithKline (GSK) moved up a spot from number six last year to round out the 2016 top five pharma companies. The UK-based drug maker's revenue grew to $37.9 billion from $35 billion last year, driven by strong sales of HIV drugs in the Pharmaceuticals segment.
The Pharmaceuticals segment is focused on providing medicines to treat a range of acute and chronic diseases. The broad portfolio includes medicines for respiratory and HIV, in which GSK are global leaders. Segment sales were approximately $20 billion. The respiratory business grew 2% driven by new products launched over the last four years, including Ellipta-based products Breo, Anoro, Arnuity and Incruse as well as biologic Nucala. HIV sales increased 37% driven primarily by strong performances from both Triumeq, a single-pill treatment combining dolutegravir, abacavir and lamivudine, and Tivicay (dolutegravir), an innovative integrase strand transfer inhibitor. The global HIV business is managed through ViiV Healthcare, a company 78.3% owned by GSK, with Pfizer and Shionogi the other shareholders. ViiV Healthcare is growing rapidly, and accounts for over 20% of Pharmaceutical sales.
GSK's Vaccines business has a broad portfolio with vaccines for people of all ages from babies and adolescents to adults and older adults. The company delivers over two million vaccine doses per day to people living in over 160 countries. Vaccines sales grew 26% roughly $4.6 billion during 2016. Performance was driven by sales of new products including meningitis vaccines Bexsero and Menveo, and there was also strong demand for Fluarix /FluLaval.
The Consumer Healthcare business, which develops and markets products in Wellness, Oral health, Nutrition and Skin health categories, includes GSK's seven global power brands--Otrivin, Panadol, parodontax, Poligrip, Sensodyne, Theraflu and Voltaren. Segment sales grew 19% to approximately $10 billion. At a brand level, Sensodyne, Panadol and Otrivin performed strongly with Sensodyne passing the $1 billion mark for the first time.
GSK reported balanced growth across its three global geographies. U.S. sales grew 9% while in Europe sales grew 12% and international market sales grew 8% for the year.
During the year GSK reported progress on several research collaborations. It exercised its option for an exclusive license to a target under the respiratory diseases research collaboration with Five Prime Therapeutics, triggering a $1.5 million payment to Five Prime. The collaboration, established in 2012, aims to identify new therapeutic approaches to treat refractory asthma and chronic obstructive pulmonary disease (COPD), with a focus on identifying novel therapeutic targets. The collaboration was expanded in April 2014 to include two additional respiratory discovery programs and the research term was extended through July 2016, which GSK committed to fund.
GSK has responsibility for further development and commercialization of products that incorporate or target the licensed protein target. Five Prime is eligible to receive as much as $93 million in milestone payments for each product incorporating the licensed protein. Five Prime is also eligible to receive royalties on sales. The Five Prime discovery platform includes a library of more than 5,700 extracellular proteins believed to encompass all of the body's medically important targets for protein therapeutics.
In another joint research effort, Adaptimmune Therapeutics and GSK expanded the terms of their collaboration agreement to accelerate Adaptimmune's lead clinical cancer program, an affinity enhanced T-cell immunotherapy (GSK3377794) targeting NYESO-1, toward pivotal trials in synovial sarcoma. Adaptimmune and GSK formed a strategic collaboration and licensing agreement in June 2014 for up to five programs, including the lead NY-ESO TCR program. GSK has an option on the NY-ESO-1 program through clinical proof of concept and, on exercise, will assume full responsibility for the program. The companies will accelerate the development of Adaptimmune's NY-ESO therapy into pivotal studies in synovial sarcoma and will explore development in myxoid round cell liposarcoma. Additionally, the companies may initiate up to eight proof-of-principle studies exploring combinations with other therapies, including checkpoint inhibitors. According to the expanded development plan, the studies will be conducted by Adaptimmune with GSK effectively funding the pivotal studies and sharing the costs of the combination studies via a success based milestone structure.
VBI Vaccines entered into a research collaboration with GSK Biologicals SA to evaluate VBI's LPV Platform. VBI's LPV Platform is a proprietary formulation and process that enables the development of vaccines and biologics with improved stability and preserved potency. GSK has the option to negotiate an exclusive license to VBI's LPV Platform for use in a defined field. Stability is a critical issue potentially affecting vaccine potency, safety and ultimately patient access. The LPV Platform uses a proprietary formulation and process to enclose and protect the antigen (active component) of a vaccine or biologic. VBI has completed proof of concept studies on a number of vaccine and biologic targets that demonstrate the LPV Platform's ability to preserve potency under stress conditions.
Lastly, Codexis, a protein engineering company, completed the third and final wave in the transfer of its CodeEvolver protein engineering platform technology to GSK, which paid $7.5 million for completion of this milestone in the second quarter of 2016. The agreement grants GSK a license to use Codexis'CodeEvolver platform technology to develop novel enzymes for use in the manufacture of GSK's pharmaceutical and health care products. Codexis has the potential to receive additional milestone payments ranging from $5.75 million to $38.5 million per project based on GSK's successful application of the licensed technology. Codexis is also eligible to receive royalties based on sales for products using Codexis' CodeEvolver technology. The CodeEvolver platform technology is operational at a GSK R&D facility in Pennsylvania.
In other news during the year, GSK opened a $90 million expansion at an antibiotics factory, enabling the pharma giant to make antibiotics for an extra 100 million patients each year at the plant in Irvine, North Ayrshire. The site has been expanded to meet growing demand from the developing world and emerging markets and the investment creates 55 new jobs with a 35% boost in capacity. The expansion is part of GSK's roughly $360 million investment in Scotland since 2013 between its sites in Irvine and Montrose, Angus. Also, an additional $260 million of investment funding was announced at the opening.
In terms of divestitures, GSK sold to Mayne Pharma a portfolio of marketed dermatology Foam Assets from for $50.1 million. The assets include U.S. rights to Fabior and Sorilux, Canadian rights to Luxiq and Olux-E and Mexican rights to betamethasone foam. Mayne Pharma acquired the approved regulatory filings, trademarks, marketing materials, select product inventory, and will acquire or obtain licenses for related patents.
WORKING WITH THE FRANCIS CRICK INSTITUTE
GSK joins forces with world-leading biomedical research center
A landmark collaboration between GSK and the Francis Crick Institute aims to achieve new breakthroughs in understanding and treating diseases. The open innovation collaboration combines GSK's pharmaceutical R&D expertise with the Crick's deep knowledge of disease biology.
The mutual aim is to explore new avenues of medical research and drug discovery across a range of diseases. The collaboration takes a 'LinkLabs' approach to working, with teams of scientists from each organization working side-by-side in integrated teams at the Crick's center of biomedical research in the heart of London and GSK's global R&D hub in Stevenage. GSK and the Crick believe this fluid interchange of skills and ideas benefits both sides, introducing new ways of working and stimulating the development of novel approaches to problems. By pooling knowledge and resources the goal of the collaboration is ultimately to improve the success rate for discovering new medicines.
In the spirit of open innovation, research findings from the collaboration will be shared externally, via joint publication in peer-reviewed journals. This will enable important discoveries to be applied across the research community, maximizing the potential to progress scientific understanding and accelerate the development of treatments for patients.
The Francis Crick Institute is a charity funded by the Medical Research Council, Cancer Research UK, the Wellcome Trust, University College London, Imperial College London and King's College London.
Headquarters: Paris, France
HEADCOUNT: 113,816 YEAR ESTABLISHED: 2004 REVENUES: $35,633 (-1%) NET INCOME: $9,782 (flat) R&D: $5,449 (+2%) DRUGS APPROVED DRUG INDICATION Kevzara rheumatoid arthritis Dupixent atopic dermatitis Suliqua type 2 diabetes Adlyxin type 2 diabetes DRUGS PENDING DRUG INDICATION Dupixent atopic dermatitis SAR342434 type 1 +2 diabetes Dengvaxia dengue fever vaccine PR5i pediatric hexav. vaccine VaxiGrip QIV IM influenza vaccine (3 years+) PHASE IIB AND BEYOND DRUG INDICATION dupilumab asthma, nasal polyposis isatuximab relapsed refractory multiple myeloma patisiran familial amyloidotic polyneuropathy GZ402666 Pompe disease sotagliflozin n type 1 & type 2 diabetes Clostridium difficile toxoid vaccine VaxiGrip QIV IM influenza vaccine (6-35 months) Pediatric pentavalent DTP-Polio-Hib vaccine Men Quad TT ACYW conjugate vaccine EARLY RESEARCH PROJECTS DRUG INDICATION SAR440340 asthma SAR439794 peanut allergy GZ402668 relapsing multiple sclerosis UshStat usher syndrome 1B SAR228810 Alzheimer's disease SAR408701 solid tumors SAR428926 cancer SAR438335 type 2 diabetes SAR341402 diabetes SAR440181 dilated cardiomyopathy SAR247799 cardiovascular indication SAR407899 microvascular angina Zika vaccine Herpes Simplex HSV-2 vaccine Virus Type 2 RSV vaccine DRUGS COMING OFF PATENT DRUG INDICATION YEAR Apidra type 1 diabetes 2018 Aldurazyme enzyme replacement 2019 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Lantus diabetes $6,020 -11% Plavix heart attack, stroke $1,627 -20% Lovenox thrombosis $1,724 -5% Polio/Pertussis/ vaccines $1,575 11% Hib Vaccines Influenza vaccines $1,602 15% Vaccines Renvela/Renagel hypocalcemia $971 -1% Aprovel /Avapro hypertention $717 -11% Cerezyme Gaucher disease $788 -1% Myozyme / Pompe disease $764 12% Lumizyme Meningitis/ vaccines $667 3% Pneumonia Vaccines
Sanofi reported revenues of $35.6 billion for 2016, dropping it from number three last year ($40.4B) to number 6 this year, due mostly to the negative impact of foreign exchange rates. The year started with Paris-based Sanofi reorganizing its business, which now consists of the following five business units: Sanofi Genzyme, the specialty care business that includes multiple sclerosis, rare diseases, and oncology; Diabetes and Cardiovascular; Generic Medicines and Emerging Markets; Consumer Healthcare; and Sanofi Pasteur, or the Human Vaccines segment. On January 1, 2017, Sanofi and Boehringer Ingelheim completed the exchange of Merial, Sanofi's animal health business and Boehringer Ingelheim's consumer healthcare business.
STRENGTHENING BIOLOGICS FOOTPRINT
Sanofi grew its biologics footprint during the year through research collaborations and facility expansions. With Global Genomics Group (G3) it entered into a research collaboration to identify new signaling pathways and targets involved in coronary artery disease. The companies will use G3's platform with data from its G3LOBAL Database to further decipher the molecular underpinnings of LDL-cholesterol regulation and to better understand which patients may benefit from interference with these signaling pathways.
In a deal with Jubilant Biosys Ltd, a Bengaluru-based subsidiary of Jubilant Life Sciences Ltd., Sanofi Deutschland GmbH, entered a strategic alliance to discover and develop small molecule inhibitors for multiple targets in metabolic disorders. The research alliance aims to develop therapeutic small molecules that will address the unmet needs in diabetes and obesity. Jubilant will provide drug discovery and early development services across computational, synthetic chemistry, biology, GLP/ GMP services, to identify lead candidates and demonstrate clinical proof of mechanism. The research for the projects take place at R&D labs of Jubilant Biosys and Jubilant Chemsys in Noida, India.
Sanofi and Innate Pharma entered a research collaboration and licensing agreement to apply Innate Pharma's new proprietary technology to the development of innovative bispecific antibody formats engaging natural killer (NK) cells to kill tumor cells through the activating receptor NKp46. Both companies will work together on the generation and evaluation of up to two bispecific NK cell engagers, using technology from Innate Pharma and Sanofi's proprietary bispecific antibody format as well as tumor targets. Sanofi will be responsible for the development, manufacturing and commercialization of products resulting from the research collaboration. Innate Pharma will be eligible to receive as much as $450 million in development and commercial milestone payments, as well as royalties on net sales.
Recursion Pharmaceuticals entered a research agreement with Sanofi Genzyme to deploy its drug repurposing platform to identify new uses for Sanofi's clinical stage molecules across dozens of genetic diseases. Recursion generates human cellular models of many diseases and uses computer vision to extract thousands of morphological measures at the level of individual cells. Molecules are then screened for their ability to rescue phenotypic defects associated with each disease. Recursion has already used the platform to generate an internal pipeline of candidates for a handful of genetic diseases, with a lead asset nearing IND for the treatment of Cerebral Cavernous Malformation. Sanofi will provide Recursion with a number of small molecules, and Recursion will screen these molecules across its extensive and rapidly expanding library of genetic disease models. Sanofi Genzyme will have the option to develop products targeting any new indications identified.
Warp Drive Bio, a life sciences company developing therapeutics that exploit the molecules and mechanisms of nature, during the year reached a milestone in the antibiotic discovery program under its research collaboration with Sanofi. Sanofi assumed all preclinical and clinical development efforts for the novel aminoglycoside antibiotic candidates discovered by Warp Drive. This program is one of several natural product-based programs utilizing Warp Dive's Genome Mining technology platform.
The Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, awarded Sanofi a $37.6 million contract to supply and manage inventory for Leukine. Sanofi Genzyme is developing Leukine for the treatment of acute radiation syndrome, a serious illness that occurs in people exposed to high doses of radiation. In 2013, Sanofi was awarded a $36.5 million contract for late stage development and procurement of Leukine. Since then Sanofi Genzyme has conducted studies regarding the potential use of Leukine in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome). The company plans to submit a supplemental Biologics License Application (sBLA) to the FDA this year.
Sanofi also unveiled plans to develop and commercialize biologics in China through a partnership with JHL Biotech, a biopharma company with development and manufacturing facilities in Wuhan and Taiwan. The two companies entered a strategic alliance to develop and commercialize biologics in China with potential international expansion.
As part of the deal, Sanofi invested $80 million in newly issued JHL shares and paid $21 million upfront to acquire exclusive rights for the proposed biosimilar of Rituximab and options to certain JHL pipeline products. JHL will lead the development, registration, and manufacturing activities, while Sanofi will lead commercialization efforts in China. JHL is entitled to receive milestones of as much as $236 million and sales royalties.
SANOFI INVESTS 340M [euro] TO EXPAND BIOLOGICS SITE IN BELGIUM
Additions to existing site will support production of monoclonal antibodies
During the year Sanofi unveiled plans for an approximately $340 million expansion at its site in Geel, Belgium, to drive the future of biologics by expanding manufacturing and commercial capabilities in order to ensure quality, capacity, and scale.
Through the investment, Sanofi plans to adapt and expand existing production capabilities to support its pipeline of monoclonal antibodies. Updates to the existing facility will include the development of new laboratories focused on quality control and manufacturing sciences.
Sanofi and its specialty care global business unit, Sanofi Genzyme, have already invested roughly $685 million in the Geel site, which began industrial biotech activities in 2001. The site is currently responsible for the global production of a protein therapy for Pompe disease, a rare, genetic muscular disease that is often fatal. The protein therapy is produced using cell cultures in large bioreactors, followed by a purification process.
Through this latest investment, the state-of-the-art facility will add more than 8,000 square meters of manufacturing floor space, enabling the site to increase its overall production capacity and diversify to other drugs and therapeutic areas.
As part of the company's strategic roadmap, Sanofi aims to launch several biologics in the upcoming years, pairing technology, cutting-edge manufacturing and operations capabilities to deliver high-quality products that could improve patient outcomes.
07 JOHNSON & JOHNSON
Headquarters: New Brunswick, NJ
HEADCOUNT: 127,000 YEAR ESTABLISHED: 1887 REVENUES: $71,890 (+3%) PHARMA REVENUES: $33,464 (+7%) NET INCOME: $16,540 (+7%) R&D: $9,095 (+1%) DRUGS APPROVED DRUG INDICATION DDarzalex relapsed/refractory multiple myeloma in combination with lenalidomide/dexamethasone Imbruvica marginal zone lymphoma in patients who require systemic therapy Stelara moderately to severely active Crohn's disease Invokamet XR once-daily, fixed-dose combination for type 2 diabetes Imbruvica previously untreated chronic lymphocytic leukaemia DRUGS PENDING DRUG INDICATION Simponi Aria ankylosing spondylitis sirukumab rheumatoid arthritis Stelara pediatric psoriasis Imbruvica chronic graft-versus-host-disease Zytiga prostate cancer newly diagnosed hormone naive metastatic PHASE IIB AND BEYOND DRUG INDICATION Xarelto reduce the risk of major adverse cardiac events, prevention of symptomatic VTE and VTE-related death, VTE prophylaxis in ambulatory cancer patients Invokana diabetic nephropathy Ulcerative Colitis ulcerative colitis, axial spondylytis Axial Spondylytis Darunavir STR single tablet regimen for HIV in treatment naive patients and treatment experienced patients Endurant STR single tablet regimen for HIV Darzalex frontline multiple myeloma transplant eligible in combination with bortezimib, thalidomide and dexamethasone Imbruvica treatment naive patients with mantle cell lymphoma, relapsed/refractory patients with indolant non-Hodgkins lymphoma, non-germinal center B-cell subtype of diffuse large B-cell lymphoma, frontline chronic lymphocytic leukemia apalutamide prostate cancer pre-metastatic castration-resistant Yondelis relapsed ovarian cancer EARLY RESEARCH PROJECTS DRUG INDICATION Ceftobiprole staphylococcal skin infections JNJ-39758979 rheumatoid arthritis CPI-1205 B-Cell lymphoma CPI-0610 leukemia, myelocytic, acute, myelodys plastic syndrome Doxazosin PTSD, alcohol use disorder Sotatercept diamond blackfan anemia VLX600 refractory cancer ALRN-6924 acute myeloid leukemia, myelodysplastic syndromes MSB0011359C solid tumors DRUGS COMING OFF PATENT DRUG INDICATION YEAR Velcade mantle cell lymphoma 2017 Remicade rheumatoid arthritis 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Remicade rheumatoid arthritis $6,966 6% Stelara psoriasis $3,232 31% Xarelto deep vein thrombosis, $2,288 23% pulmonary embolism Zytiga prostate cancer $2,260 1% Invega Sustenna schizophrenia $2,214 21% Prezista HIV/AIDS $1,851 2% Simponi rheumatoid arthritis $1,745 31% Invokana type 2 diabetes $1,407 7% Imbruvica oncology $1,251 82% Velcade velcade, mantle $1,224 -8% cell lymphoma
Headquartered in New Brunswick, NJ, Johnson & Johnson 0&J) operates in more than 60 countries while its pharmaceutical and healthcare products are supplied to over 200 countries. The Pharmaceutical segment contributes nearly 47% of J&J's total revenues. The segment reported 2016 revenues of $33.5 billion--a 7% increase over 2015--and comprises several franchises: Immunology, Infectious Disease, Neuroscience, Oncology, and Cardiovascular and Metabolics. The major blockbuster drugs under the Immunology franchise are Remicade, Stelara, and Simponi/Simponi Aria. The franchise revenues reported growth of 7% to $12 billion in 2016.
J&J's Oncology franchise grew 24% to $6 billion during 2016, driven by increased sales of Imbruvica and a strong uptake of Darzalex. During the year Janssen Biotech, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, entered several cancer collaborations. First it teamed up with Tesaro for exclusive rights to the investigational compound niraparib in prostate cancer. Niraparib is an orally administered, once daily, potent, and highly selective poly polymerase (PARP) inhibitor, currently in late-stage development for patients with metastatic breast cancer and ovarian cancer. Janssen will develop and commercialize niraparib for patients with prostate cancer worldwide, except in Japan. Tesaro received an upfront payment of $35 million, and is eligible to receive additional milestone payments of up to $415 million.
With Bristol-Myers Squibb (BMS), Janssen entered a clinical research collaboration to evaluate BMS' immuno-oncology drug Opdivo (nivolumab) and Janssen's Live Attenuated Double-Deleted (LADD) Listerial monocytogenes cancer immunotherapy, expressing mesothelin and EGFRvIII (JNJ-64041757), in patients with non-small cell lung cancer (NSCLC). Opdivo is a human antibody designed to alleviate immune suppression. JNJ-64041757 is designed to induce an immune response against NSCLC tumors.
Later in the year, Janssen entered into a master clinical trial collaboration and supply agreement with Onyx Pharmaceuticals, a subsidiary of Amgen, to evaluate the efficacy and safety of CD38-directed immunotherapy daratumumab (DARZALEX) in combination with a proteasome inhibitor (PI) carfilzomib (KYPROLIS) and dexamethasone. The agreement covers all potential opportunities for combining daratumumab and carfilzomib to treat cancer. Janssen licensed daratumumab from Genmab and is responsible for all global development, marketing and manufacturing. Carfilzomib is developed and commercialized by Amgen.
Industrial bioscience company Amyris entered into a research agreement with Janssen facilitated by Johnson & Johnson Innovation. The collaboration will use Amyris's [micro]Pharm platform technology to develop a customized library of natural and natural-like compounds to test against Janssen's therapeutic target. Amyris's pPharm platform technology enables an integrated discovery and production process for therapeutic compounds. It provides access to scarce natural compounds and also creates new diversity based on natural compound scaffolds.
Janssen Biotech also licensed Ionis Pharmaceuticals' IONIS-JBIl-2.5Rx, an oral antisense drug for the treatment of a GI autoimmune disease, for $10 million. Janssen assumes all global development, regulatory and commercialization responsibilities after Ionis completes the IND-enabling studies. Ionis is eligible to receive as much as $800 million in development, regulatory and sales milestones and license fees for three programs, as well as royalties on sales from any product that is successfully commercialized.
Janssen Pharmaceutica NV divested five anesthesia and pain management injectable products to Piramal Enterprises' wholly owned Critical Care subsidiary in the UK for $155 million. The products include five injectable versions of Janssen's Sublimaze (fentanyl citrate), Sufenta (sufentanil citrate), Rapifen (alfentanil hydrochloride), Dipidolor (piritramide), and Hypnomidate (etomidate), which are currently marketed in more than 50 countries. Piramal acquired the brand names and related IP, including how to make both the API and the finished dosage forms of the products. The acquisition does not include the transfer of any manufacturing facilities or employees. Janssen will continue to supply finished dosage forms for up to three years and API for up to five years, and will continue to sell the products on behalf of Piramal until the marketing authorizations or relevant business relations are transferred to Piramal.
J&J BUYS ACTELION FOR $30B
Actelion to spin out R&D ops and assets
During the year Johnson & Johnson entered into a mega deal to acquire Actelion Ltd. for approximately $30 billion.
Actelion, based in Allschwil, Switzerland, has a franchise of differentiated, innovative products for pulmonary arterial hypertension (PAH), as well as specialty in-market medicines and late-stage products. J&J expects to retain Actelion's presence in Switzerland and leverage its complementary capabilities to shape medical paradigms.
As part of the transaction, Actelion will spin out its drug discovery operations and early-stage clinical development assets into a newly created Swiss biopharma company, R&D NewCo. Johnson & Johnson also received an option on ACT-132577, a product being developed for resistant hypertension currently in Phase II development.
08 GILEAD SCIENCES
Headquarters: Foster City, CA
HEADCOUNT: 8,900 YEAR ESTABLISHED: 1987 REVENUES: $30,390 (-7%) NET INCOME: $13,488 (-26%) R&D: $5,098 (+69%) DRUGS APPROVED DRUG INDICATION Harvoni and Sovaldi pediatric patients 12 years and older with HCV infection Vemlidy chronic hepatitis B virus Once-Daily Truvada reducing the risk of sexually acquired HIV-1 Epclusa all genotypes of chronic hepatitis C Odefsey STR HIV-1 infection DRUGS PENDING DRUG INDICATION Sofosbuvir, chronic HCV infection velpatasvir and voxilaprevir STR Bictegravir/F/TAF HIV/AIDS PHASE IIB AND BEYOND DRUG INDICATION Selonsertib NASH Idelalisib relapsed refractory CLL Andecaliximab gastric cancer Filgotinib Crohn's disease, ulcerative colitis Entospletinib chronic graft versus host disease Presatovir respiratory syncytial virus GS-9876 rheumatoid arthritis, Sjogren's syndrome, cutaneous lupus erythematosus GS-5734 Ebola virus infection EARLY RESEARCH PROJECTS DRUG INDICATION GS-9620 HIV/AIDS GS-9688 chronic HBV infection Andecaliximab solid tumors GS-5829 solid tumors DRUGS COMING OFF PATENT DRUG INDICATION YEAR Atripla HIV 2018 Complera HIV 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Harvoni chronic hepatitis C $9,081 -34% Sovaldi chronic hepatitis C $4,001 -24% Truvada HIV $3,566 3% Atripla HIV $2,605 -15% Stribild HIV $1,914 5% Epclusa chronic hepatitis C $1,752 n/a Complera / HIV $1,457 2% Eviplera Viread chronic hepatitis B $1,186 7%
Despite having lost a portion of its dominant share in the increasingly competitive Hep C market, Gilead only slipped one slot in this year's rankings to 8. While the company took a hit financially, with revenues down 7% and earnings down 26%, it was expected, and Gilead's competitors reaped the rewards.
HCV product sales, which consist of Harvoni, Sovaldi and Epclusa were $14.8 billion for the year, compared to $19.1 billion in 2015. Declines were due to lower sales of Harvoni and Sovaldi, partially offset by sales of Epclusa, which was launched in 2016 in various countries.
R&D expenses, which were up a whopping 69% in 2016, increased primarily due to overall clinical costs, including ongoing milestone payments, and Gilead's purchase of a U.S. EDA priority review voucher. R&D expenses also include up-front collaboration expenses related to Gilead's license and collaboration agreement with Galapagos NV, purchase of Nimbus Apollo, Inc. and impairment charges related to IPR&D.
Despite key competition and fewer patients, due to the curative nature of its Hep C products, a large untapped market remains and Gilead has been working to build awareness among an estimated 2.5 million baby boomers in the U.S. If Gilead can maintain its market share in this segment, there is still money to be made.
With its multi-billion dollar HCV franchise, Gilead's closest competitors remain far behind. Even though Merck, AbbVie, and BMS each have HCV drugs for at least one of the six genotypes, their combined sales don't touch Gilead's numbers. Additionally, Gilead's newest pan-genotype drug Epclusa, approved last June, surpassed its competition in 2016 with $1.8 billion in sales, and it should have a strong hold in the near term.
Epclusa represents the first all-oral, pan-genotypic, single tablet regimen for the treatment genotype 1-6 chronic hepatitis C virus (HCV) infection. It's also the first single tablet regimen approved for the treatment of patients with HCV genotype 2 and 3, without the need for ribavirin.
Despite high cure rates and simplified treatment for most HCV patients, those who have failed previous treatment with direct acting antivirals continue to represent an unmet medical need. Study results demonstrate that combining three potent antivirals with different mechanisms of action and high barriers to resistance can provide high cure rates for patients who have failed other highly effective oral DAA regimens.
Gilead's pending SOF/VEL/VOX fixed-dose combination was granted Breakthrough Therapy designation by the U.S. FDA for the treatment of chronic genotype 1 HCV patients who previously failed an NS5A inhibitor-containing regimen.
Additionally, the European Commission approved Gilead's Vemlidy (Tenofovir Alafenamide,TAF) for the treatment of Chronic Hepatitis B Virus Infection, which is the first new treatment for chronic hepatitis B to be approved in Europe in nearly a decade. TAF is a targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to Viread, but at one-tenth the dose. TAF is associated with improved renal and bone lab safety parameters compared to TDF in clinical trials.
Vemlidy was approved by the FDA in November 2016 for the treatment of chronic HBV infection in adults with compensated liver disease, and by the Japanese Ministry of Health, Labour and Welfare in December 2016 for the suppression of viral replication in chronic hepatitis B patients with evidence of hepatitis B virus replication and abnormal liver function.
In the near term, Gilead has decent growth potential. Within the next few years. Bictegravir could significantly boost HIV franchise sales. Bictegravir is a combo alternative integrase inhibitor that would come in single tablet form. GSK's Tivicay has led the market in this space with its HIV segment up 57% in the first quarter, led by Tivicay sales. Gilead stands to recoup some of the market share it lost in this space once Bictegravir hits the market.
Recent trials demonstrated that Gilead's bictegravir combination could offer an improvement over existing therapies. In four Phase III studies, bictegravir met its primary objective of noninferiority. Gilead plans to submit a marketing authorization application for BIC/FTC/TAF in the EU in the third quarter of 2017.
Three of the ongoing studies are designed to explore the safety and efficacy of BIC/FTC/TAF compared to triple-therapy regimens containing dolutegravir in treatment-naive patients and virologically suppressed patients switching from an existing antiretroviral regimen with dolutegravir. A fourth study in virologically suppressed patients compares switching to BIC/FTC/TAF versus remaining on a suppressive regimen of two nucleoside/ nucleotide reverse transcriptase inhibitors and protease inhibitor.
Because people with HIV are living longer and are increasingly likely to be taking medication for other conditions, such as heart and liver disease, they are exposed for longer periods of time to the virus and to the medications used to treat it. Therefore, new, effective treatment options are needed that are also tolerable, and offer convenient dosing.
Helping to fulfill this need, Gilead's once-daily single tablet regimen Odefsey for the treatment of HIV-1 in certain patients, was granted approval in the EU in June 2016, and in the U.S. in March 2016. Odefsey combines Gilead's emtricitabine and tenofovir alafenamide (marketed as Descovy) with rilpivirine, marketed by Janssen Sciences Ireland UC, a Johnson & Johnson company. Following the approval of Genvoya in November 2015, Odefsey is Gilead's second STR based on the Descovy backbone to receive marketing authorization in the EU and is currently the smallest pill of any STR for the treatment of HIV.
Additionally, the European Commission approved Gilead's once-daily Truvada for reducing the risk of sexually acquired HIVl. This represents the first antiretroviral medicine to be licensed in Europe for pre-exposure prevention, in combination with safersex practices, to reduce the risk of HIV-1 in high risk adults.
To maintain its position in the top 10, Gilead needs a new outlet. So far, its oncology efforts have been challenged. Its only approved oncology asset is idelalisib, marketed as Zydelig, which is a second line therapy with boxed warning in three indications: Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior therapies; and Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior therapies. Needless to say, Zydelig hasn't taken off in the oncology sector as anticipated.
Other oncology pipeline assets include: Andecaliximab, an MMP9 inhibitor currently in Phase III trials in gastric cancer, entospletinib, a SYK inhibitor in Phase II in acute myeloid leukemia, and hematopoietic and lymphoid malignancies; and tirabrutinib, a BTK inhibitor in Phase II for B-cell malignancies, as well as couple candidates in early development.
In November, Gilead achieved top-line results from two Phase III trials (SIMPLIFY 1 and 2) that evaluated momelotinib, an investigational inhibitor of Janus kinase 0AK) compared to ruxolitinib or best alternative therapy (BAT) in myelofibrosis, a relatively rare bone marrow cancer. The SIMPLIFY-1 study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for splenic response rate, defined as the percentage of patients experiencing a 35% reduction in spleen volume, but SIMPLIFY-2 failed to achieve its primary endpoint of superiority of momelotinib compared to BAT in patients previously treated with ruxolitinib.
In the "other" category, NASH, or nonalcoholic steatohepatitis, is a therapeutic area being pursued by Gilead, and several other drug developers. Allied Market Research estimates that the global market is expected to reach $1.6 billion by 2020. The high prevalence of Type II diabetes and obesity, which leads to NASH and other nonalcoholic fatty liver diseases, has created this market. North America has the highest rates of NASH and other nonalcoholic fatty liver diseases and Europe ranks second in terms of the prevalence.
Results from a Phase II trial evaluating the investigational apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib alone or in combination with the monoclonal antibody simtuzumab (SIM) in NASH and moderate to severe liver fibrosis, demonstrated regression in fibrosis that was, in parallel, associated with reductions in other measures of liver injury in patients treated with selonsertib.
While competition for Gilead's top franchises took its toll in 2016, HCV and HIV assets moving through the pipeline are likely to put this antiviral authority back on top--remaining there may prove more difficult. A breakthrough product in oncology, cell therapy, or NASH is needed in the long term.
Headquarters: North Chicago, IL
HEADCOUNT: 29,000 YEAR ESTABLISHED: 2013 REVENUES: $25,638 (+12%) NET INCOME: $5,953 (+16%) R&D: $4,366 (+2%) DRUGS APPROVED DRUG INDICATION Humira hidradenitis suppurativa, uveitis Venclexta chronic lymphocytic leukemia with 17p deletion Imbruvica relapsed/refractory marginal zone lymphoma Empliciti multiple myeloma, second line Duodopa Parkinson's disease Zinbryta multiple sclerosis DRUGS PENDING DRUG INDICATION Imbruvica graft-versus-host-disease glecaprevir/ GT1 -6 chronic hepatitis C virus pibrentasvir PHASE IIB AND BEYOND DRUG INDICATION ABT-494 rheumatoid arthritis Risankizumab psoriasis Empliciti first line multiple myeloma Imbruvica diffuse large B-cell lymphoma, follicular lymphoma, pancreatic cancer Rova-T small cell lung cancer Veliparib breast cancer, lung cancer, ovarian cancer Venclexta chronic lymphocytic leukemia, multiple myeloma, acute myeloid leukemia Atrasentan diabetic nephropathy Elagolix endometriosis, uterine fibroids EARLY RESEARCH PROJECTS DRUG INDICATION ABBV-323 Crohn's disease ABBV-553 psoriasis ABBV-599 rheumatoid arthritis ABBV-075 acute myeloid leukemia, multiple myeloma ABBV-085 solid tumors ABBV-621 solid and hematologic tumors ABBV-838 multiple myeloma ABT-414 pediatric brain tumors ABT-RTA 408 melanoma ABBV-951 Parkinson's disease ABT-555 multiple sclerosis ABBV-2451 cystic fibrosis DRUGS COMING OFF PATENT DRUG INDICATION YEAR Humira rheumatoid arthritis 2018 Kaletra HIV/AIDS 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Humira rheumatoid arthritis $16,078 15% Imbruvica chronic lymphocytic $1,832 143% leukemia Viekira hepatitis C $1,522 -7% Lupron hormone treatment $821 -1% Synthroid hyperthyroidism $763 1% Synagis RSV $730 -2% Creon digestion $730 16% AndroGel testosterone $675 -3% Kaletra HIV/AIDS $549 -22% Sevoflurane anesthesia $428 -10%
In 2016 AbbVie delivered its best year yet since it launched in 2013 after separating from Abbott Laboratories. With strong growth performance, new product launches and the addition of Stemcentrx to advance its work within oncology, AbbVie delivered revenue growth of more than 13% to $25.6 billion, placing it as the ninth largest pharma company in the world.
AbbVie operates in one business segment--pharmaceutical products. Its blockbuster biologic Humira (adalimumab), which is used to treat a range of autoimmune diseases, continues to anchor the company accounting for more than 60% of total revenues. The rising star in AbbVie's portfolio is the cancer drug Imbruvica, whose sales shot up 143% to $1.8 billion in 2016. The company also offers products for Virology, Metabolics/Hormones, Endocrinology.
In 2016, AbbVie launched several new products and expanded indications across immunology, oncology, virology and neuroscience. The company also advanced its research in oncology with Stemcentrx and its novel compound, rovalpituzumab tesirine (Rova-T), which is currently in late-stage clinical trials for solid tumor cancers.
AbbVie made the mega deal to acquire Stemcentrx and its lead late-stage asset Rova-T for $5.8 billion in April 2016. The company says Rova-T is a novel biomarker-specific therapy that is derived from cancer stem cells and targets delta-like protein 3 (DLL3) that is expressed in more than 80% of SCLC patient tumors and is not present in healthy tissue. AbbVie boasts an oncology development program of more than 200 clinical trials across more than 20 tumor types.
At the beginning of the year, MD Anderson Cancer Center and AbbVie entered a three-year immunotherapy collaboration to select and conduct preclinical and clinical studies evaluating new ideas in the area of immuno-oncology. AbbVie's research efforts in immunotherapy leverage the companys 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.
At the end of the year, AbbVie and Northwestern University signed a five-year collaboration agreement to advance research and discovery in oncology. AbbVie and the Robert H. Lurie Comprehensive Cancer Center of Northwestern will work in several areas of oncology research, including, lung, colorectal, breast, prostate and hematological cancer.
The collaboration provides Lurie Cancer Center scientists with the opportunity to access new therapies developed by AbbVie for preclinical research funded under the agreement, as well as AbbVie's research teams. AbbVie has the option to obtain an exclusive license of certain Lurie Cancer Center discoveries made under the five-year collaboration.
AbbVie set up additional collaborations with several other companies. One with Boehringer Ingelheim aims to develop and commercialize BI 655066, an anti-IL-23 monoclonal antibody in Phase III development for psoriasis. The companies are also evaluating the drug's potential in Crohn's disease, psoriatic arthritis and asthma. In addition to the anti-IL-23 antibody, AbbVie gains rights to an anti-CD-40 antibody, BI 655064, currently in Phase I development. Boehringer will retain responsibility for further development of BI 655064, and AbbVie may elect to advance the program after certain undisclosed clinical achievements.
AbbVie also formed a collaboration with Argenx, a clinical-stage biopharmaceutical company, to develop and commercialize ARGX115, Argenx'preclinical human antibody program targeting the novel immuno-oncology target GARR a protein believed to contribute to immuno-suppressive effects of T-cells. Argenx will conduct research and development through IND-enabling studies. Upon successful completion of these studies, AbbVie may exercise an exclusive option to license the ARGX-115 program and assume responsibility for further clinical development and commercialization. In addition to the ARGX-115 program, and upon reaching a predetermined preclinical stage milestone, AbbVie will fund further GARP-related research by Argenx for an initial period of two years.
CytomX Therapeutics teamed up with AbbVie to co-develop and commercialize Probody Drug Conjugates against CD71, which is highly expressed in a number of solid and hematologic cancers and has molecular properties for efficient delivery of cytotoxic payloads to tumor cells. Probody therapeutics are designed enhance the tumor-targeting features of an antibody and reduce drug activity in healthy tissues. CytomX has generated preclinical data that demonstrates that Probody drug conjugates can safely and effectively target tumor antigens, such as CD71, that are not addressable by conventional antibody-drug conjugates.
Lastly, Galapagos NV and AbbVie expanded their agreement in cystic fibrosis (CF) to reflect the successful expansion of their CF portfolio. The companies aim to develop a triple CFTR combination therapy to address 90% of patients with CF. In order to bring a more effective therapy to patients, the companies have developed multiple candidates and backups for each of the three components of a potential triple combination.
ABBVIE OPENS FIRST PHASE OF SINGAPORE FACILITY
New site to expand the company's global operations for small molecule and biologics manufacturing
AbbVie has strengthened its manufacturing capabilities by opening the small molecule active pharmaceutical ingredient (API) facility of its Singapore manufacturing site. This facility supports the growth of AbbVie's oncology and women's health pipeline and reflects progress from AbbVie's two previous announcements for manufacturing investment in Asia in 2014.
The new 120,000 square-meter site located in the Tuas Biomedical Park is AbbVie's first manufacturing facility in Asia and will also include a biologics manufacturing facility that is expected to be fully operational by the end of 2018. Combined, the API and biologics facilities represent a $320 million investment in Singapore that will employ more than 250 new employees, the majority of whom will be hired locally in Singapore, including skilled positions across manufacturing, technical operations, administration, quality, information technology and supply chain.
Headquarters: London, UK
HEADCOUNT: 59,700 YEAR ESTABLISHED: 1999 REVENUES: $23,002 (-7%) NET INCOME: $3,406 (+21%) R&D: $5,890 (-2%) DRUGS APPROVED DRUG INDICATION Tagrisso NSCLC patients with EGFR T790M mutation Qtern type-2 diabetes Siliq moderate-to-severe plaque psoriasis Zavicefta serious bacterial infections DRUGS PENDING DRUG INDICATION ZS-9 hyperkalaemia DRUGS IN PHASE MB AND BEYOND DRUG INDICATION acalabrutinib B-cell malignancy, 1st line CLL durvalumab s2nd-line advanced bladder cancer, stage III NSCLC durvalumab 3rd-line NSCLC, 1 st-line bladder, 2nd-line + tremelimumab SCCHN, 3rd-line NSCLC, 1 st-line bladder, 2nd-line SCCHN moxetumomab hairy cell leukaemia pasudotox elumetinib differentiated thyroid cancer Epanova severe hypertriglyceridaemia Farxiga/Forxiga type-2 diabetes roxadustat anaemia in CKD/ESRD Bevespi Aerosphere COPD benralizumab severe asthma, COPD tralokinumab severe asthma anifrolumab systemic lupus erythematosus lanabecestat early Alzheimer's disease EARLY RESEARCH PROJECTS DRUG INDICATION AZD0156 solid tumors AZD2811 solid tumors AZD9150 haematological malignancies AZD9496 ER+ breast cancer AZD4635 solid tumors AZD6738 solid tumors Lynparza + AZD1775 solid tumors MEDI-565 solid tumors MEDI-0562 solid tumors MEDI-3726 prostate cancer durvalumab solid tumors + AZD1775 durvalumab non-small cell lung cancer + Iressa durvalumab melanoma + dabrafenib + trametinib durvalumab or diffuse large B-cell lymphoma durvalumab +AZD9150 tremelimumab solid tumors + MEDI0562 DRUGS COMING OFF PATENT DRUG INDICATION YEAR Onglyza diabetes 2018 Pulmicort asthma 2018 Nexium acid reflux 2018 Symbicort asthma 2017-2029 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Crestor cholesterol $3,401 -32% Symbicort asthma $2,989 -12% Nexium acid reflux $2,032 -19% Pulmicort asthma $1,061 5% Brilinta antiplatelet $839 36% Farxiga type 2 diabetes $835 70% Faslodex breast cancer $830 18% Zoladex cancer $816 0% Seloken/Toprol-XL hypertention $737 4% Seroquel XR anti-psychotic $735 -28%
AstraZeneca rounded out this year's top ten pharma companies with $23 billion of revenues in 2016. While this is a 5% drop from the previous year, moving forward the company has classified several products and regions as a part of its growth platforms--Respiratory and Diabetes products, Brilinta/Brilique, and the regional sales from emerging markets and Japan. The company also added a new Oncology franchise for the first time to the growth platforms, with its new oncology products, Tagrisso and Lynparza.
Overall, the Cardiovascular and Metabolic Diseases segment is AstraZeneca's highest revenue-contributing segment, with about 38% contribution of total product sales. Revenues fell 13% to $8.1 billion in 2016 due to the decrease in its Crestor sales following patent expiry and a generic entry in the U.S. Sales of Onglyza in the U.S. declined 10% to $376 million, as the company prioritized Farxiga. A highlight for the segment was the performance of new growth products Brilinta/Brilique whose revenues rose 39% to $839 million during 2016.
The Respiratory segment's revenues fell 3% to $4.8 billion during 2016, with lower sales of Symbicort and Tudorza/ Eklira. This decrease was partially offset by increased revenues of drugs including Pulmicort, Duaklir, and Daliresp. Pulmicort sales of $1 billion were up 5%.
The Oncology segment, which as mentioned above, is now included in the growth platform, includes new products Tagrisso and Lynparza that are expected to drive this segment's growth in coming years. The segment's revenues rose 16% to $3.4 billion during 2016, following a strong performance of Tagrisso, Lynparza, Zoladex, and Faslodex. The segment's revenues were partially offset by lower sales of Iressa and legacy products such as Casodex and Arimidex. Lynparza reported sales of $218 million and was available in 31 countries by end 2016. Iressa sales of $513 million were down 6% as the company prioritized Tagrisso
The Other segment includes drugs from the Infection, Neuroscience, and Gastrointestinal franchises. This is AstraZeneca's second-largest revenue contributor, comprising 24% of the company's total product sales for 2016, which fell 19% during the year. Nexium sales of $2 billion were down 19% and Seroquel XR sales of $735 million were down 28% following loss of exclusivity.
FEEDING THE PIPELINE
During the year AstraZeneca, along with its global biologics research and development arm, MedImmune, and Moderna Therapeutics formed a new collaboration to discover, co-develop and co-commercialize messenger RNA (mRNA) therapeutic candidates for the treatment of a range of cancers. The collaboration is in addition to the agreement announced by the companies in 2013 to develop mRNA Therapeutics for the treatment of cardiovascular, metabolic and renal diseases as well as selected targets in oncology. The collaboration combines Medlmmune's protein engineering and cancer biology expertise with Moderna's mRNA platform. mRNA-based therapies are an innovative treatment approach that enables the body to produce therapeutic protein in vivo, opening up new treatment options for a wide range of diseases that, according to the company, cannot be addressed using existing technologies.
AstraZeneca and Moderna have agreed to collaborate on two specific immuno-oncology programs, based on promising preclinical data, including pharmacology in tumor models. Moderna will fund and be responsible for discovery and preclinical development of product candidates, with the aim of delivering one investigational new drug (IND) application-ready molecule for each of the two programs.
Also during the year, Allergan entered into a global agreement with AstraZeneca to develop and commercialize ATM-AVI, an investigational, fixed-dose antibiotic combining aztreonam and avibactam. The companies will evaluate the combination to treat serious infections caused by metallo [beta]lactamase MBL-producing Gram-negative pathogens, a difficult-to-treat sub-type of carbapenem-resistant Enterobacteriaceae (CRE), for which there are limited treatments. Aliergan will maintain commercialization rights in the U.S. and Canada and AstraZeneca will have commercialization rights in all other countries.
ATM-AVT is the first drug candidate to be developed under a public-private partnership agreement between AstraZeneca and the Biomedical Advanced Research and Development Authority (BARDA), a part of the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response (ASPR). The goal of this strategic alliance is to develop a portfolio of drug candidates over the next five years with dual uses in treating illnesses caused by bioterrorism agents and antibiotic-resistant infections.
LEO Pharma formed an agreement with AstraZeneca to acquire the global license to tralokinumab in skin diseases and the exclusive license to brodalumab in Europe. Tralokinumab, an anti-IL-13 monoclonal antibody, has completed a Phase lib study for the treatment of patients with atopic dermatitis. Brodalumab is an IL-17 receptor monoclonal antibody under regulatory review for patients with moderate-to-severe plaque psoriasis. AstraZeneca received $115 million upfront and is eligible to receive as much as $1 billion in commercial-related milestones and a percentage of royalties on sales. AstraZeneca will manufacture and supply tralokinumab to LEO Pharma and will retain all rights to tralokinumab in respiratory disease and any other indications outside of dermatology.
Eli Lilly and Co. and AstraZeneca entered a worldwide agreement to co-develop MEDI1814, an antibody selective for amyloid-beta 42 (A[beta]42) as a potential disease-modifying treatment for Alzheimer's disease. This agreement expands the collaboration related to AZD3293, a BACE inhibitor in Phase III development.
AstraZeneca and Incyte Corporation formed a collaboration to evaluate the efficacy and safety of Incyte's Janus-associated kinase 0AK) 1 inhibitor, INCB39110, in combination with AstraZeneca's next generation epidermal growth factor receptor (EGFR) inhibitor, Tagrisso (osimertinib). The combination will be assessed as a second line treatment for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who have been treated with a first generation EGFR tyrosine kinase inhibitor (TKI) and subsequently developed the T790M resistance mutation.
Headquarters: Thousand Oaks, CA
HEADCOUNT: 20,000 YEAR ESTABLISHED: 1980 REVENUES: $22,991 (+6%) NET INCOME: $7,722 (+11%) R&D: $3,840 (-6%) DRUGS APPROVED/LAUNCHED DRUG INDICATION Amgevita inflammatory diseases Parsabiv secondary hyperparathyroidism Enbrel children with moderate to severe plaque psoriasis Blincyto Ph- relapsed or refractory B-cell precursor acute lymphoblastic leukemia DRUGS PENDING DRUG INDICATION Repatha additional reduction in heart attacks, strokes and coronary revascularizations Erenumab migraine prevention Xvega multiple myeloma Blincyto relapsed/refractory Ph+ and minimal residual disease of ALL ABP 215 biosimilar to Bevacizumab Romosozumab osteoporosis in postmenopausal women at increased risk of fracture DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION AMG 520 Alzheimer's disease Aranesp low risk myelodysplastic syndromes Enbrel psoriatic arthritis, maintaining remission of rheumatoid arthritis Erenumab episodic and chronic migraine Evenity postmenopausal osteoporosis and male osteoporosis Imlygic metastatic melanoma Kyprolis multiple myeloma, small-cell lung cancer Omecamtiv heart failure Prolia glucocorticoid-induced osteoporosis Repatha hyperlipidemia Vectibix wild-type KRAS exon 2 metastatic colorectal cancer Xvega prevention of bone metastases in patients with adjuvant breast cancer EARLY RESEARCH PROJECTS DRUG INDICATION AMG 176 multiple myeloma AMG 211 cancer AMG 224 multiple myeloma AMG 301 migraine AMG 330 acute myeloid leukemia AMG 420 multiple myeloma AMG 557 systemic lupus erythematosus AMG 570 systemic lupus erythematosus AMG 592 inflammatory diseases AMG 820 cancer AMG 986 heart failure IMLYGIC metastatic melanoma Oprozomib multiple myeloma DRUGS COMING OFF PATENT DRUG INDICATION YEAR Sensipar/Mimpara renal disease 2018 Enbrel psoriasis 2019 Blincyto Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia 2019 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Enbrel rheumatoid arthritis $5,965 11% Neulasta chemotherapy induced $4,648 -1% neutropenia Aranesp chemotherapy induced $2,093 7% anemia Prolia bone cancer $1,635 25% Sensipar/ renal disease $1,415 12% Mimpara Xgeva bone cancer $1,405 9% Epogen anemia $1,282 -31% Neupogen chemotherapy induced $765 -27% neutropenia Kyprolis multiple myeloma $692 35% Vectibix colorectal cancer $611 11% Nplate immune thromboytopenia $584 11%
After nearly 40 years, Amgen remains among the world's largest biopharma companies with a market cap of $114 billion. In 2016, Amgen's portfolio of top sellers boasted seven blockbuster drugs (classified as $1 billion or more in annual sales). Of these, five are still growing, Enbrel, Aranesp, Prolia, Sensipar and Xgeva. Osteoporosis drug Prolia, has shown the strongest gains (25%) over the last year. However, biosimilar competition in today's market is fierce and Amgen's products are among the prime targets.
Enbrel sales soared 11% in 2016, just shy of $6 billion, while sales of Neulasta, a treatment for chemotherapy induced neutropenia, were pretty much flat at $4.6 billion due to increased competition in this space and patent expirations. Sales of Amgen's original flagship blockbusters, Epogen and Neupogen (the industry's first victim of biosimilar competition), have fallen dramatically in recent years, down a third since 2014.
Kyprolis, Blincyto and Repatha are Amgen's fastest growing drugs but they have a way to go to compensate for the decline of core products.
Despite increased competition and patent expirations, 10 out of Amgen's 13 products grew in 2016. Not unlike many of its competitors, advancing its pipeline assets is essential to maintaining growth. Amgevita and Erenumab look to be the most promising sources of revenue for the company in the near term.
Safety issues surrounding Evenity and less than impressive Repatha results are among the company's most recent road blocks. Osteoporosis drug Evenity was close to gaining FDA approval, but a recent study showed an increased risk of heart-related side effects. It's not likely to be approved this year and its future is in question. Also, Repatha, a new cholesterol reducing drug, showed positive results in a recent study but not enough to impress investors or outstrip the competition, and as a result, it could face tougher payer reimbursement.
In the way of positive news, Amgen submitted a Biologics License Application to the FDA for its new migraine drug Erenumab, which demonstrated positive Phase III results from pivotal studies in more than 2,600 patients with episodic and chronic migraine.
Amgen and development partner, Novartis, recently expanded their collaboration for erenumab, a fully human monoclonal antibody specifically designed to target and block the Calcitonin Gene-Related Peptide (CGRP) receptor, believed to have a critical role in mediating migraine pain. The companies have agreed to combine capabilities to co-commercialize erenumab in the U.S. Amgen retains exclusive rights in Japan and Novartis gains exclusive rights in Canada, retaining its existing rights in rest of the world.
Amgevita, Amgen's biosimilar to AbbVie's $16 billion top-seller Humira, was approved by the FDA and the EU, but ongoing litigation could significantly delay launch. Amjevita is the first Humira biosimilar to be approved in the U.S.
AbbVie filed a lawsuit seeking to block Amgen from selling a copy of the arthritis medicine, and according to AbbVie, Amgen's proposed biosimilar would infringe at least 10 patents, and AbbVie has reserved the right to assert as many as 51 other patents. Unfortunately for Amgen, the trial is not expected to begin until November 2019, and Amgen is not alone in its pursuit for a Humira biosimilar. Samsung Bioepsis' Imraldi was recently recommended for approval by the EMA. The EMA also recently accepted an application for review from Sandoz, and Boehringer Ingelheim's recent Phase III study confirmed its biosimilar candidate has similar efficacy, safety and immunogenicity to Humira--just to name a few ...
Moreover, with respect to the Sandoz v. Amgen dispute, on June 12, the U.S. Supreme Court released a highly anticipated decision relating to patent disputes between the developers of new biologics and the manufacturers of "biosimilar" copies.
Sandoz received approval from the European Commission for Erelzi, its biosimilar to Amgen's Enbrel to treat inflammatory diseases such as rheumatoid arthritis, psoriasis, and psoriatic arthritis.
On one issue, Sandoz won. As a result of the court's ruling, biosimilar companies will generally be able to launch their products as soon as the data exclusivity on the innovative product expires. On the second issue, however, the outcome was a bit murky. Amgen lost the immediate dispute presented to the Supreme Court, but the litigation is not over, and there are still key questions to be resolved concerning not only federal but also state law, namely California.
With respect to innovation efforts, two early stage R&D investments aim to target cancer. Amgen and Immatics Biotechnologies entered a research collaboration and exclusive license agreement to develop next-gen T-cell engaging bispecific immunotherapies targeting multiple cancers. Amgen paid $30 million upfront and Immatics is eligible to receive more than $500 million in development, regulatory and commercial milestones, as well as royalties on sales.
Additionally, Amgen acquired global rights from Boehringer Ingelheim for BI 836908 (AMG 420), a bispecific T cell engager (BiTE) that targets B-cell maturation antigen, a potential target for multiple myeloma. The drug is currently in Phase I studies. The companies will work together on clinical development, transfer of manufacturing, and global regulatory activity.
Among assets closer to fruition, Amgen will sponsor a clinical trial collaboration and supply agreement with Janssen Biotech that will evaluate the efficacy and safety of CD38-directed immunotherapy Darzalex, in combination with Amgen's proteasome inhibitor Kyprolis and dexamethasone, to treat cancer. The first Phase III study will determine if this combination improves survival compared to Kyprolis and dexamethasone alone in multiple myeloma in patients who have received prior therapies.
Also, Amgen and Daiichi Sankyo Co. entered an exclusive agreement to commercialize nine biosimilars in Japan. The deal includes several biosimilars in late-stage development, including biosimilars of Humira, Avastin and Herceptin. Amgen is responsible for the development and manufacturing of the biosimilars and Daiichi Sankyo will file for marketing approval and be responsible for distribution and commercialization in Japan.
Despite current challenges, Amgen's strong foundation as a biologics pioneer should prevail. Near term assets and strong revenue streams for top sellers should offset any losses for flagship products--for now.
Headquarters: Petach Tivka, Israel
HEADCOUNT: 57,000 YEAR ESTABLISHED: 1901 REVENUES: $21,903 (+11%) SPECIALTY PHARMA REVENUES: $8,674 (+4%) NET INCOME: $311 (-81%) R&D: $2,111 (+38%) DRUGS APPROVED DRUG INDICATION Vantrela ER pain Austedo Huntington's disease ArmonAir RespiClick asthma AirDuo RespiClick asthma DRUGS PENDING DRUG INDICATION Austedo Tardive dyskinesia QVAR asthma Reslizumab IV asthma Fluticasone Propional te asthma Fluticasone Salmetert 3l asthma PHASE IIB AND BEYOND DRUG INDICATION Fremanezumab chronic migraine, cluster headache Fasinumab osteoarthritis pain Reslizumab SC asthma CT-P10 biosimilar to Rituxan CT-P6 biosimilar to Herceptin EARLY RESEARCH PROJECTS DRUG INDICATION Omacetaxine acute myeloid leukemia pridopidine Huntington's disease Omacetaxine chronic myeloid leukemia mepesuccinate PXVX0047 adenoviral infection Cisplatin and ovarian cancer doxorubicin DRUGS COMING OFF PATENT DRUG INDICATION YEAR Treanda cancer 2019 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Copaxone multiple sclerosis $4,223 5% Treanda cancer $661 -11% ProAir asthma $565 3% Qvar asthma $462 18% Azilect Parkinson's disease $410 7% Nuvigil insomnia $200 -46%
Headquartered in Israel, Teva is the world's largest generic medicines producer, leveraging its portfolio of more than 1,800 molecules to produce a wide range of generic products in nearly every therapeutic area. In specialty medicines, Teva has the world-leading innovative treatment for multiple sclerosis (MS) as well as late-stage development programs for other disorders of the central nervous system (CNS), including movement disorders, migraine, pain and neurodegenerative conditions, as well as a broad portfolio of respiratory products.
The Generic medicines segment includes chemical and therapeutic equivalents of originator medicines in a variety of dosage forms, such as tablets, capsules, injectables, inhalants, liquids, ointments and creams. Teva is the leading generic drug company in the U.S. and Europe. This segment includes the OTC business, conducted primarily through PGT, a consumer healthcare joint venture with P&G, as well as its active pharmaceutical ingredient (API) manufacturing business.
Specialty medicines includes Teva's core therapeutic areas of CNS medicines such as Copaxone and Azilect and respiratory medicines such as ProAir and QVAR. The specialty medicines segment also includes products in other therapeutic areas, such as Bendeka/Treanda in oncology and ParaGard in women's health.
Teva's revenues in 2016 were $21.9 billion, up from $19.6 the year before. The Generics segment makes up 55% of sales, followed by the Specialty (39%) and Other (6%) segments. In geographic terms, the U.S. accounts for the bulk of sales with a 53% share, followed by Europe (25%) and ROW markets (22%).
Of note during the year, in August, Teva completed its acquisition of Allergan's worldwide generic pharmaceuticals business, Actavis Generics. At closing, Teva paid Allergan roughly $33.4 billion. The acquisition significantly expanded its generics product portfolio and pipeline, and R&D capabilities.
As part of the Actavis acquisition, Teva divested certain products in the U.S. and Europe, to meet antitrust regulatory requirements. It sold its Actavis Generics assets and operations in the UK and Ireland to Accord Healthcare for approximately $768 million. The sale included a portfolio of generic medicines plus a manufacturing plant in Barnstaple, England.
During the year, Mayne Pharma completed its $652 million transaction with Teva and Allergan, gaining 37 approved and five filed generic pharmaceutical products. This transaction is among the largest generic pharmaceutical divestitures and followed Teva's purchase of Allergan's generic drug business.
Also, Impax Laboratories signed definitive agreements with Teva and affiliates of Allergan for the acquisition of a broad portfolio of generic products across solid oral, inhalable, injectable and topical dosage forms for $586 million. The deal also includes the return to Impax of its rights to its pending abbreviated new drug application (ANDA) for the generic equivalent to Concerta (methylphenidate hydrochloride).
In October 2016, Teva completed the acquisition of Anda Inc., the fourth largest distributor of generic pharmaceuticals in the U.S., from Allergan for $500 million.
During the year, Teva entered into a collaborative agreement with Regeneron Pharmaceuticals to develop and commercialize Regeneron's pain medication product, fasinumab. It paid Regeneron $250 million upfront and will share the global commercial benefits of this product, as well as ongoing associated research and development costs of approximately $1 billion, equally with Regeneron. Following the termination of the Phase II clinical study for chronic low back pain in October 2016, Teva and Regeneron planned to design a Phase III study in chronic low back pain that excludes patients with advanced osteoarthritis.
Teva and Celltrion entered into an exclusive partnership to commercialize two of Celltrion's mAb biosimilar candidates in the U.S. and Canada. CT-P10 is a proposed mAb biosimilar to Rituxan (rituximab), which is used to treat Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Rheumatoid Arthritis (RA), Wegener's Granulomatosis and Microscopic Polyangiitis (MPA). CT-P6 is a proposed mAb biosimilar to Herceptin (trastuzumab), which is used to treat HER2-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Rituxan and Herceptin have combined annual sales of approximately $6.5 billion in the U.S. and Canada. Teva will be responsible for all commercial activities in the U.S. and Canada, pending regulatory approvals. Celltrion has responsibility for completing all clinical development and regulatory activities. Celltrion receiveed $160 million upfront.
Teva also completed the acquisition of Representaciones e Investigaciones Medicas, S.A. de C.V. (Rimsa), a pharmaceutical manufacturing and distribution company in Mexico, for $2.3 billion. It also established a new business venture with Takeda--Teva Takeda Yakuhin Ltd.--to address the growing importance of generics in Japan.
At the end of the year, Teva entered into an agreement to sell its royalties and other rights in Ninlaro (ixazomib) to a subsidiary of Takeda, for a $150 million upfront payment, with additional consideration of up to $150 million dependent on future sales. Also, it entered into a license agreement for research, development, manufacture and commercializing of Attenukine with a subsidiary of Takeda, for a $30 million upfront payment, with additional milestone payments of up to $280 million and royalties.
TEVA, ABCELLERA EXPAND RESEARCH COLLABORATION
Follows a successful mAb discovery alliance completed between the two companies last year
Canadian biotechnology company AbCellera Biologies has entered a new therapeutic antibody discovery collaboration with Teva to discover new antibodies against membrane protein targets.
The current agreement follows a successful first collaboration completed between the two companies last year.
The deal will see AbCellera Biologies use its monoclonal antibody (mAb) screening platform to support the discovery of antibodies that modulate the function of an undisclosed membrane protein target elected by Teva Pharmaceutical.
As part of the agreement, AbCellera will receive an upfront payment and research support, in addition to milestone and royalty payments based on Teva's development and commercialization of antibodies generated under the current partnership. Further terms of the agreement have not yet been disclosed.
AbCellera founding chief executive officer Carl Hansen said, "We are excited to expand our relationship with the innovative team at Teva. This follow-on project marks an important step in establishing AbCellera's platform as an enabling technology for difficult target classes that have proven intractable by conventional antibody discovery methods."
Steffen Nockm, senior vice-president and global head, Teva Pharmaceutical Industries, said, "We are pleased to extend our work with AbCellera utilising this company's novel biologics technology. This agreement will be complementary to our existing antibody discovery process, with the potential to strengthen Teva's capabilities in novel biologics discovery."
Headquarters: Indianapolis, IN
HEADCOUNT: 42,066 YEAR ESTABLISHED: 1876 REVENUES: $21,222 (+6%) NET INCOME: $2,738 (+14%) R&D: $5,244 (+9%) DRUGS APPROVED DRUG INDICATION Synjardy cardiovascular outcomes Jardiance reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease Lartruvo soft tissue sarcoma with doxorubicin DRUGS PENDING DRUG INDICATION Baricitinib rheumatoid arthritis PHASE IIB AND BEYOND DRUG INDICATION nasal glucagon severe hypoglycemia LY3314814 Alzheimer's disease Lasmiditan migraine Galcanezumab chronic and episodic migraine Solanezumab Alzheimer's disease Tanezumab pain indications including osteoarthritis pain Abemaciclib metastatic breast cancer, KRAS mutant non small cell lung cancer Ixekizumab axial spondyloarthritis Empagliflozin chronic heart failure Ramucirumab first-line gastric cancer, 2nd line hepatocellular carcinoma EARLY RESEARCH PROJECTS DRUG INDICATION BAFF/IL-17 immune diseases CXCR1/2 immune diseases DGAT-2 inhibitor dyslipidemia GIP/GLP-1 diabetes Co-agonist Peptide Insulin-Fc/Dula diabetes Oxyntomodulin diabetes AB42 Antibody Alzheimer's disease D1 potentiator dementia N3pG-AB Monoclonal Alzheimer's disease Antibody Tau Antibody Alzheimer's disease Angiopoietin 2 MAb cancer CSF-1R Monoclonal cancer Antibody FGFR3-ADC cancer TGF[beta] RI Kinase cancer DRUGS COMING OFF PATENT DRUG INDICATION YEAR Cialis erectile dysfunction 2017 Strattera ADHD 2017 Effient anticoagulant 2017 Forteo osteoporosis 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Humalog diabetes $2,769 -3% Cialis erectile dysfunction $2,472 7% Alimta cancer $2,283 -8% Forteo osteoporosis $1,500 11% Humulin diabetes $1,366 4% Cymbalta anxiety, depression $931 -9% Strattera ADHD $855 9% Zyprexa schizophrenia $725 -23% Erbitux head and neck cancer $687 42% Effient anticoagulant $535 2%
While Lilly dropped a spot to number 13 this year revenues were up from $19.9 billion to $21.2 billion in 2016. U.S. sales were $11.5 billion while outside the U.S. sales were $9.7 billion. The Indianapolis, IN-based company reported revenue growth across its three largest therapeutic areas. The Endocrinology segment increased 15% to $8 billion primarily driven by growth of Trulicity, Forteo, Jardiance, Trajenta, and Basaglar. Oncology grew 6% to $3.7 billion due to higher volumes for Cyramza and Erbitux, and Cardiovascular grew 5% to $3.2 billion, mostly due to higher realized price for Cialis. Revenue in Neuroscience decreased 7% to $2.7 billion as a result of lower volumes for Zyprexa and Cymbalta following patent expirations.
On the drug development front, the company reported two new molecular entities (NMEs) were approved by regulatory authorities in 2016, Ixekizumab (Taltz), a neutralizing monoclonal antibody to interleukin-17A for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, and Olaratumab (Lartruvo), a human lgG1 monoclonal antibody for the treatment of advanced soft tissue sarcoma.
During the year, Lilly continued its successful Alzheimer's disease collaboration with AstraZeneca. It received Fast Track designation from the FDA for the AZD3293 development program, an oral beta secretase cleaving enzyme (BACE) inhibitor currently in Phase III trials. The FDA's Fast Track program is designed to expedite the development and review of new therapies to treat serious conditions and tackle key unmet medical needs.
AZD3293 has been shown in Phase I studies to reduce levels of amyloid beta in the cerebro-spinal fluid of people with Alzheimer's and healthy volunteers. The progression of Alzheimer's disease is characterized by the accumulation of amyloid plaque in the brain. BACE is an enzyme associated with the development of amyloid beta and inhibiting BACE is expected to prevent the formation of amyloid plaque and eventually slow the progression of the disease.
AstraZeneca received a $100 million milestone payment from Lilly now that AZD3293 has moved into Phase III testing in the Amaranth study.
The two companies also announced the planned initiation of a new Phase III trial for AZD3293, named Daybreak,which will study the safety and efficacy of AZD3293 in people with mild Alzheimer's dementia.
The alliance between the two companies was formed in 2014 for the development and commercialization of AZD3293/ LY3314814. Lilly leads clinical development, working with researchers from AstraZeneca's neuroscience research and development team, while AstraZeneca is responsible for manufacturing. The companies have joint responsibility for commercialization of the molecule and will share all future costs equally for development and commercialization, as well as net global revenues post-launch.
In another Alzheimer's alliance, Lilly and AstraZeneca are codeveloping MEDI1814, an antibody selective for amyloid-beta 42 (A[beta]42), which is in Phase I development. AstraZeneca received a $30 million upfront payment from Lilly.
In another clinical trial collaboration, Lilly and Boehringer Ingelheim teamed up to battle metastatic breast cancer. The collaboration will evaluate the safety and tolerability of abemaciclib (LY2835219), Lilly's cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor, in combination with BI 836845, Boehringer's insulin-like growth factor (IGF)-1/IGF-2 ligand neutralizing antibody, in patients diagnosed with HR+, HER2- mBC. Based on the Phase lb trial results, the collaboration has the potential to expand to Phase II trials in patients with HR+, HER2- mBC and other solid tumors.
Lilly's abemaciclib is designed to block the growth of cancer cells by specifically inhibiting CDK 4 and CDK 6. In many cancers, uncontrolled cell growth arises from a loss of control in regulating the cell cycle due to increased signaling from CDK 4 and CDK 6. Boehringer's BI 836845 is an IGF ligand-neutralizing antibody that binds to both IGF-1 and IGF-2 preventing activation of the respective receptor, resulting in decreased growth-promoting signaling, which may decrease tumor growth. In a Phase lb/ II trial, BI 836845 has shown promising preliminary efficacy and good clinical safety in combination with everolimus and exemestane in patients with HR+ mBC.
The rationale for the collaboration is based upon the hypothesis that these two agents, in combination, could offer a more complete pathway interference and could potentially prolong cell cycle arrest. For HR+, HER2- mBC patients, this could translate to a reversal of resistance to hormone therapy.
Lastly, Regen BioPharma entered into an agreement with Lilly to receive compounds for drug discovery purposes and allows Regen to share structural information on compounds of mutual interest. Regen will examine 21,000 Lilly compounds in its NR2F6 high-throughput screening program to identify activators and inhibitors of this protein. NR2F6 is a molecular switch known as an "orphan nuclear receptor," which controls genes associated with the immune response as well as genes associated with the ability of cancer stem cells to propagate. Lilly has an option to negotiate a compound purchase agreement, a license agreement, or a research collaboration agreement for further research and development of material of mutual interest.
DAVE RICKS TAKES LILLY'S HELM
John Lechleiter retires as CEO
At the end of 2016 John Lechleiter retired as president and chief executive officer of Lilly, a post he held since 2008. He joined Lilly in 1979 as a senior organic chemist in process research and development. In the mid1980s he served as director of pharmaceutical product development for the Lilly Research Centre Limited in England. He later held roles in project management, regulatory affairs, product development, and pharma operations. In 2005, he was named president and chief operating officer and joined the board of directors.
Mr. Lechleiter's successor is Dave Ricks, who has served as president and chief executive officer of Lilly since January 1, 2017. He became chairman of the board of directors on June 1,2017. A 20-year Lilly veteran, Mr. Ricks served as president of Lilly Bio-Medicines from 2012 to 2016. Previously, he was president of Lilly USA, the company's largest Dave Ricks affiliate, from 2009 to 2012. He served as president and general manager of Lilly China, operating in one of the world's fastest-growing emerging markets, from 2008 to 2009. He was also general manager of Lilly Canada from 2005 to 2008, after roles as director of pharmaceutical marketing and national sales director in that country. Mr. Ricks joined Lilly in 1996 as a business development associate and held several management roles in U.S. marketing and sales before moving to Lilly Canada.
14 BRISTOL-MYERS SQUIBB
Headquarters: New York, NY
HEADCOUNT: 25,000 YEAR ESTABLISHED: 1887 REVENUES: $19,427 (+17%) NET INCOME: $4,457 (+185%) R&D: $4,940 (-17%) DRUGS APPROVED DRUG INDICATION Opdivo squamous cell cancer of the head and neck, dMMR or MSI-H metastatic colorectal cancer, relapsed or refractory classical Hodgkin lymphoma (cHL) Orencia highly active and progressive disease in adult patients with rheumatoid arthritis Empliciti multiple myeloma DRUGS PENDING DRUG INDICATION Opdivo advanced or metastatic urothelial carcinoma, dMMR or MSI-H metastatic colorectal cancer PHASE IIB AND BEYOND DRUG INDICATION Prostvac oncology Opdivo adjuvant melanoma , 1 st line head and neck, 1 st line glioblastoma, 1 st line hepatocellular carcinoma Opdivo + Yervoy 1st line non-small cell lung cancer, 1st line small cell lung cancer, 1 st line renal cell carcinoma, 1st line head and neck, 1st line gastric cancer Opdivo + Empliciti multiple myeloma Empliciti multiple myeloma PROSTVAC metastatic castration--resistant prostate cancer EARLY RESEARCH PROJECTS DRUG INDICATION Factor Xla Inhibitor thrombosis HSP47 fibrosis PEG-FGF21 fibrosis Anti-IP10 ulcerative colitis BTK Max rheumatoid arthritis S1P1 Agonist autoimmune diseases TYK2 Inhibitor autoimmune diseases Nivolumab immunoscience Anti-CD73 solid tumors Anti-GITR solid tumors Anti-OX40 solid tumors Anti-TIGIT solid tumors Cabiralizumab solid tumors Glypican3-ADC hepatocellular carcinoma Mesothelin-ADC solid tumors DRUGS COMING OFF PATENT DRUG INDICATION YEAR Reyataz HIV/AIDS 2017 Sustiva HIV/AIDS 2017 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Opdivo melanoma, lung $3,774 301% cancer, renal cancer Eliquis deep vein thrombosis $3,343 80% and pulmonary embolism Orencia rheumatoid arthritis $2,265 20% Sprycel leukemia $1,824 13% Hepatitis C HCV $1,578 -2% Franchise Baraclude hepatitis B $1,192 -9% Sustiva HIV/AIDS $1,065 -15% Franchise Yervoy oncology $1,053 -6% Reyataz HIV/AIDS $912 -20% renal cancer
Headquartered in New York City, Bristol-Myers Squibb's (BMS) sales grew 17% to $19.4 billion in 2016 from $16.5 billion the year before. Most of the revenue comes from sales in the U.S. (55%) while Europe accounts for 22% and ROW markets including Japan contributed 23 % of sales revenue.
Overall, growth was driven by strong performance in the company's Oncology segment, the largest revenue contributor in 2016, accounting for nearly 35% of the company's total revenue. This segment reported a rise of more than 62% in 2016 compared to 2015, mainly driven by Opdivo, with nearly $3.8 billion in sales, up a staggering 301%. Yervoy, Sprycel, and newly launched Empliciti to treat multiple myeloma, also contributed to growth.
The Virology segment contributed 24% of BMS's total revenue, which fell 11% to $4.7 billion in 2016, compared to $5.3 billion in 2015. With increased competition in this segment, the company reported declines for all of its products, including its Hepatitis C franchise, its hepatitis B drug Baraclude, and its HIV drugs Reyataz and Sustiva.
The Immuno-Science segment, which includes Orencia, contributed nearly 12% of the company's total revenue in 2016, driven by a 20% increase in Orencia sales to $2.3 billion compared to 2015.
The Cardiovascular segment, represented by the drug Eliquis, contributed 17% of BMS's total revenue in 2016. Eliquis sales soared 80% to $3.3 billion in 2016, compared to $1.9 billion in 2015, due to wide use and the strength of its prescription trends.
The Neuroscience segment, represented by the drug Ability, reported a drop of 83% in Abilify revenue to $128 million following competition launched during the year.
Also, the Matured Products segment and all other products showed a 17% drop in revenue to $2.1 billion due to increased competition.
In 2016, BMS received 19 approvals for new medicines and additional indications and formulations of currently marketed medicines in major markets--the U.S., EU and Japan--as well as multiple regulatory milestone achievements for Opdivo. BMS also said it encountered a significant setback in first-line lung cancer with the announcement of negative results of CheckMate-026. As a result, BMS did not pursue an accelerated regulatory pathway for the Opdivo+Yervoy combination therapy in first-line lung cancer, but BMS is still pursuing a broad program in this area encompassing combinations of Opdivo+Yervoy, Opdivo and chemotherapy, and Opdivo combined with Yervoy and chemotherapy.
ACQUISITIONS AND PARTNERSHIPS
BMS made several acquisitions and entered licensing transactions to focus resources on growth opportunities that drive the greatest long-term value. BMS is focused on the following core therapeutic areas: oncology, including IO, immunoscience, cardiovascular and fibrotic diseases. Significant transactions from 2016 are summarized below.
In December, BMS and Nitto Denko entered into an exclusive worldwide license agreement granting BMS the right to develop and commercialize Nitto Denko's investigational siRNA molecules targeting HSP47 in vitamin A containing formulations, which includes Nitto Denko's lead asset ND-L02-s0201, currently in a Phase lb study for the treatment of advanced liver fibrosis.
The agreement also grants BMS the option to receive exclusive licenses for HSP47 siRNAs in vitamin A containing formulations for the treatment of lung fibrosis and other organ fibrosis.
In July 2016, BMS acquired all of the outstanding shares of Cormorant, a private pharmaceutical company focused on the development of therapies for cancer and rare diseases. The acquisition provides BMS with full rights to Cormorant's lead candidate HuMax-IL8, a Phase I/II monoclonal antibody that represents a potentially complementary IO mechanism of action to T-cell directed antibodies and co-stimulatory molecules.
In April 2016, BMS acquired all of the outstanding shares of Padlock, a private biotechnology company dedicated to creating new medicines to treat destructive autoimmune diseases. The acquisition provides BMS with full rights to Padlock's PAD inhibitor discovery program focused on the development of potentially transformational treatment approaches for patients with rheumatoid arthritis. Padlock's PAD discovery program may have additional utility in treating systemic lupus erythematosus and other autoimmune diseases.
In February 2016, BMS and Pfizer entered into a collaboration and license agreement with Portola to develop and commercialize the investigational agent andexanet alfa in Japan. Andexanet alfa is designed to reverse the anticoagulant activity of Factor Xa inhibitors, including Eliquis. BMS and Pfizer are responsible for all development and regulatory activities for andexanet alfa in Japan and for exclusively commercializing the agent in Japan. Portola retains the rights to andexanet alfa outside of Japan and will be responsible for the manufacturing supply.
In addition to the above transactions, BMS provided notice of terminations to the California Institute for Biomedical Research pertaining to a research collaboration agreement for the development of anti-fibrotic preclinical compounds and Dual Therapeutics pertaining to a research collaboration agreement for the development of anti-cancer preclinical compounds.
BMS OPENS EXPANDED BIOLOGICS FACILITY
$280 Million Project Increases Workforce, Adds New Capabilities
In May 2016, BMS completed a major expansion at its Devens, MA biologics facility designed to accelerate development of the company's growing portfolio of biologics.
The $280 million project adds two new buildings to the 89-acre Devens campus: a Biologics Development Building for designing processes for the early production of investigational medicines, and a Clinical Manufacturing Building where investigational medicines will be produced to support clinical trials. Both are new capabilities for Devens, a site that had previously focused solely on large-scale, bulk biologics manufacturing.
The expansion increases the site's workforce, with approximately 200 new jobs having been added at the project's initial completion rising to approximately 350 jobs over time. The two new buildings also add approximately 200,000 square feet to a site now comprised of eight major buildings in a 600,000 square-foot complex. In addition, the buildings add to the major investment the company has made at Devens, a former military base. When combined with the company's initial $750 million investment to build the facility, the expansion project brings the company's total investment at the site to more than $1 billion.
Headquarters: Leverkusen, Germany
HEADCOUNT: 115,200 YEAR ESTABLISHED: 1971 REVENUES: $49,274 (-3%) PHARMA REVENUES: $17,300 (+15%) NET INCOME: $4,330 (-4%) R&D: $2,936 (+15%) DRUGS APPROVED DRUG INDICATION Kovaltry hemophilia A Xofigo castration-resistant prostate cancer and bone metastases Gadavist / Gadovist contrast agent for supra-aortic or renal artery disease Kyleena low-dose levonorgestrel-releasing intra-uterine system Stivarga second-line unresectable hepatocellular carcinoma DRUGS PENDING DRUG INDICATION Regorafenib second-line treatment for unresectable liver cancer Rivaroxaban secondary prophylaxis of acute coronary syndrome DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION Amikacin Inhale pulmonary infection BAY 1841788 non-metastatic castration-resistant prostate cancer, metastatic hormone- sensitive prostate cancer Ciprofloxacin DPI non-cystic fibrosis bronchiectasis Copanlisib various forms of non-Hodgkin lymphoma Damoctocog alfa hemophilia A pegol Finerenone diabetic kidney disease Radium-223 dichloride combination treatment of castration- resistant prostate cancer Regorafenib colon cancer, adjuvant therapy Rivaroxaban prevention of major adverse cardiac events, anticoagulation in chronic heart failure, prevention of venous thromboembolism, peripheral artery disease Tedizolid pulmonary infection Vericiguat chronic heart failure DRUGS COMING OFF PATENT DRUG INDICATION YEAR Levitra erectile dysfunction 2018 Avelox antibiotic 2019 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Xarelto atrial fibrillation $3,085 25% Eylea macular degeneration $1,712 28% Kogenate hemophilia $1,228 -3% Mirena women's health $1,099 4% Nexavar oncolgy $917 -6% Betaferon multiple sclerosis $773 -14% Yaz women's health $714 -7% Adalat hypertension $657 -5% Aspirin Cardio cardiovascular $567 -1% Glucobay diabetes $543 -5%
Leverkusen, Germany-based Bayer rounds out this year's top 15, jumping up four spots from number 19 on $17.3 billion in revenues, which grew from $15 billion in 2015. The Pharmaceuticals segment focuses on cardiology and women's healthcare, and on specialty therapeutics in the areas of oncology, hematology and ophthalmology.
Pharmaceuticals performed well driven by key growth products, including the cardiovascular drug Xarelto, and Eylea, for macular degeneration. Xarelto sales jumped 25% to $3 billion, due to expanded volumes in Europe and Japan, while Eylea also made substantial gains, seeing its sales rise 28% to $1.7 billion.
PHASE III AND BEYOND
In May 2016, a Phase III study investigating regorafenib (Stivarga) in unresectable liver cancer reached its primary endpoint, a statistically significant improvement of overall survival. The study investigated regorafenib in patients with hepatocellular carcinoma whose disease had further progressed during prior treatment with sorafenib (Nexavar). Based on these data, it submitted regorafenib for marketing authorization for the treatment of unresectable liver cancer in Europe, Japan and the U.S. in 3Q16.
In June 2016, Bayer agreed with Orion Corp. to expand the global clinical development program for the androgen receptor (AR) antagonist BAY-1841788 (ODM-201). A new Phase III study is evaluating BAY-1841788 in men with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) who are starting first-line hormone therapy.
Also in June, Bayer formed a new research partnership with the U.S. National Surgical Adjuvant Breast and Bowel Project (NSABP) for a Phase III study that will investigate regorafenib as a single agent for adjuvant treatment following completion of standard adjuvant chemotherapy in patients with advanced but not yet metastatic colon cancer.
In September 2016, a Phase III trial was initiated to evaluate vericiguat, a soluble guanylate cyclase (sGC) stimulator, in patients suffering from chronic heart failure with reduced ejection fraction. The development and commercialization of vericiguat are part of the worldwide strategic collaboration between Bayer and Merck & Co. in the field of sGC modulation.
In terms of filings and approvals during the year, in February 2016, Bayer received approval from the European Commission for Kovaltry for the treatment of hemophilia A in patients of all age groups. Kovaltry is an unmodified recombinant factor VIII product that in clinical trials has demonstrated efficacy and tolerability as an on-demand therapy and for prophylactic use two or three times per week by hemophilia A patients. In March 2016, Kovaltry was approved by the FDA and the Japanese Ministry of Health, Labour and Welfare (MHLW).
Also in March 2016, the Japanese MHLW granted marketing authorization for Xofigo for the treatment of adult patients with castration-resistant prostate cancer and bone metastases.
In May 2016, the FDA approved Gadavist/Gadovist (gadobutrol) as the first contrast agent for use with magnetic resonance angiography (MRA) to evaluate known or suspected supra-aortic or renal artery disease in patients of all ages.
Additionally, the FDA approved Bayer's new low-dose levonorgestrel-releasing intrauterine system with the brand name Kyleena. The new system releases the lowest daily hormone dose in an intrauterine system for up to five years of protection against pregnancy. Bayer also completed the corresponding decentralized registration procedure for the EU. On this basis, it is expected that the health authorities of the EU member states will grant national marketing authorizations in the coming months.
In November 2016, an expansion of indications was filed for Stivarga (regorafenib) in the U.S., Japan and Europe. The filings pertain to the second-line treatment of patients with unresectable hepatocellular carcinoma. The FDA granted priority review status to regorafenib in the registration process for the expansion of indications. The Japanese Ministry of Health, Labour and Welfare (MHLW) granted priority review status for the registration filing in January 2017.
During the year, Bayer entered several partnerships to advance its drug development initiatives. Bayer and Evotec entered into a five-year, multi-target research partnership to develop multiple clinical candidates for the treatment of kidney diseases such as chronic kidney disease in diabetes patients. Both companies will contribute drug targets and a comprehensive set of high-quality technology platforms to jointly develop innovative treatment options for these severe conditions. The partners will share responsibilities during preclinical development of potential candidates.
Bayer receives exclusive access to selected candidates as well as to Evotec's CureNephron target pipeline. Bayer will be responsible for any subsequent clinical development and commercialization. Evotec will receive a minimum of 14 million [euro] over the contract period including research payments and an undisclosed license fee. In addition, Evotec is eligible to receive preclinical, clinical and sales milestones of potentially over 300 million [euro].
Back in 2012, Bayer and Evotec entered into a five-year partnership in the therapeutic area of endometriosis. Currently in its fourth year, this alliance has delivered four preclinical candidates and one first-in-class clinical program has been initiated.
Bayer and X-Chem entered an expanded global drug discovery collaboration across multiple therapeutic areas and target classes. Bayer has expanded access to X-Chem's DEX technology, which is based on DNA-encoded libraries of small molecules with more than 120 billion molecules. The collaboration aims to discover lead structures for complex drug targets in areas of high unmet medical need. X-Chem received an upfront payment, research and development funding, as well as development milestones totaling as much as $528 million. Bayer has an exclusive option to license any programs under the collaboration. X-Chem will also receive royalties and sales milestones. The companies have been working together since 2012 and Bayer has licensed two programs of small molecules from X-Chem that address complex target structures such as protein:protein interactions. The new multi-year collaboration expands the scope and duration of the partnership.
Regeneron Pharmaceuticals and Bayer will jointly develop a combination therapy of the angiopoietin2 (Ang2) antibody nesvacumab and the vascular endothelial growth factor (VEGF) trap aflibercept, for the treatment of serious eye diseases. Two separate Phase II studies are evaluating the combination therapy as a co-formulated single intravitreal injection in patients with wet age-related macular degeneration or diabetic macular edema.
Preclinical data demonstrates that angiopoietins act together with the VEGF family to promote the formation and maturation of blood and lymphatic vessels in the eye. Ang2 and VEGF together therefore have the potential to influence the pathological development of new blood vessels and the permeability of blood vessel walls in certain diseases of the eye.
Regeneron and Bayer currently collaborate on the global development and commercialization of Eylea (aflibercept) Injection and on the global development of REGN2176-3, the Platelet Derived Growth Factor Receptor Beta (PDGFR-beta) antibody rinucumab co-formulated in a single intravitreal injection with aflibercept, which is currently in Phase II trials in patients with wet age-related macular degeneration.
With the Broad Institute it formed a strategic partnership in the field of genome and drug research in cardiology aimed at using findings from human genetics to develop new cardiovascular therapies, and in the field of oncology, to identify and develop active ingredients that target tumor-specific gene alterations.
Also, with the German Cancer Research Center it formed a partnership for the development of new therapeutic options in oncology, especially in immunotherapy. It teamed up with ImmunoGen in the field of antibody-drug conjugates (ADCs) for novel tumor therapies. With Janssen Research & Development, Bayer is furthering development of Xarelto (rivaroxaban), and with MorphoSys AG, partnered on antibody-drug conjugates using MorphoSys's HuCAL technology.
Headquarters: Ingelheim, Germany
HEADCOUNT: 45,692 YEAR ESTABLISHED: 1817 REVENUES: $16,699 (+3%) NET INCOME: $1,952 (+13%) R&D: $3,279 (flat) DRUGS APPROVED DRUG INDICATION Tiotropium Respimat asthma maintenance treatment Jardiance reduce the risk of cardiovascular death in type 2 diabetes DRUGS PENDING DRUG INDICATION BI 695501 biosimilar candidate to Humira Glyxambi fixed dose combination, type 2 diabetes PHASE MB AND BEYOND DRUG INDICATION Empagliflozin heart failure Nintedanib lung diseases, coloretal cancer alteplase stroke Idarucizumab hemorrhage BI 695502 colorectal neoplasms Afatinib NSCLC, head and neck cancer HCP1202 COPD EARLY RESEARCH PROJECTS DRUG INDICATION BI 836845 castrate resistant prostate cancer BI 655130 psoriasis BI 836826 chronic, B-cell lymphocytic leukemia BI 836880 solid tumors BI 836909 multiple myeloma BI 836858 acute myeloid leukemia BI 690517 diabetic kidney disease DRUGS COMING OFF PATENT DRUG INDICATION YEAR Combivent Respimat COPD 2018 Spiriva COPD 2018 Mirapex restless legs syndrome 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Spiriva COPD $3,155 -19% Pradaxa atrial fibrillation $1,459 4% Trajenta type 2 diabetes $1,188 20% Micardis hypertension $1,010 -3%
While Boehringer's top seller Spiriva fell faster than expected in 2016, diabetes drug Jardiance, with $460 million in sales, has the potential to surpass the company's flagship product. With its new cardiovascular label, which was approved in the U.S. at the end of last year, EvaluatePharma estimates that 2017 in-market Jardiance revenues could top $929 million, rising to $3.5 billion by 2022.
Over the course of the next few years, Jardiance prospects could be further augmented if upcoming trials succeed in chronic heart failure patients with or without diabetes. However, Jardiance will compete with other products in the SGLT2 inhibitor class. Contenders include Johnson & Johnson's Invokana, with trial results expected this year, and Astrazeneca's Farxiga.
Boehringer has not been at the forefront of the immuno-oncology revolution, but it's trying to make a mark in this field with a focus on combinations, specifically with cancer vaccines. Its strategy hinges on developing its anti-PD-1 antibody, BI 754091, which is only in Phase I development. The company plans to pair BI 754091 with various cancer vaccine approaches, including those using peptides, RNA and vectors, the most advanced of which are currently in clinical development.
The company also expanded its immuo-oncology efforts via an alliance with ViraTherapeutics to jointly develop a next-gen oncolytic virus therapy platform and to investigate ViraTherapeutic's lead candidate VSV-GP alone and with other therapies.
Boehringer's biosimilar endeavors include both early and late stage assets. Following postive results from the Phase III VOLTAIRE-RA study of its adalimumab biosimilar candidate BI 695501, the company is seeking regulatory approval from the FDA and EMA. Also, in a Phase I study, its bevacizumab biosimilar candidate has demonstrated bioequivalence to Avastin, an angiogenesis inhibitor that is used to treat a variety of cancers.
In the way of investments, the company established a digital lab as an independent subsidiary focused on digital solutions in healthcare, and opened a commercial production site for biopharmaceuticals in China. With the founding of BI X, Boehringer will develop prototypes for new products and solutions and test them with the company's business units in pilot phases to help ensure that data accrued at BI X are being quickly integrated into the digital lab's parent house.
Additionally, as part of the company's efforts to grow its contract development and manufacturing of mAbs and recombinant proteins in China, the company recently opened a commercial production site in Shanghai. With an initial investment of more than 70 million [euro], the site represents the first biopharma facility established by a leading, multinational biopharma manufacturer in China utilizing mammalian cell culture technology.
17 NOVO NORDISK
Headquarters: Bagsvaerd, Denmark
HEADCOUNT: 42,446 YEAR ESTABLISHED: 1989 REVENUES: $15,841 (flat) NET INCOME: $5,375 (+5%) R&D: $2,064 (+4%) DRUGS APPROVED DRUG INDICATION Xultophy diabetes Rebinyn haemophilia B Fiasp diabetes DRUGS PENDING DRUG INDICATION Semaglutide type 2 diabetes PHASE IIB AND BEYOND DRUG INDICATION Oral semaglutide type 2 diabetes N8-GP haemophilia A Somapacitan growth disorder EARLY RESEARCH PROJECTS DRUG INDICATION LAI287 type 1 and 2 diabetes PI406 type 1 and 2 diabetes PYY 1562 type 2 diabetes, obesity AM833 obesity GG-co-agonist 1177 obesity FGF21 obesity Tri-agonist 1706 obesity Concizumab haemophilia A and B Subcutaneous N8-GP haemophilia A and B DRUGS COMING OFF PATENT DRUG INDICATION YEAR Levemir diabetes 2019 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Victoza diabetes $2,841 8% NovoRapid diabetes $2,827 -7% Levemir diabetes $2,421 -10% Human insulins diabetes $1,572 -4% NovoMix diabetes $1,485 -9% Norditropin HGH deficiency $1,243 9%
As the prevalence of diabetes has grown in the U.S. and around the world, so too has the demand for effective treatments. In response, Novo Nordisk, the Denmark-based diabetes giant, made two major expansion announcements in 2016. First, in April, it unveiled plans to invest more than $110 million 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.
Novo Nordisk has invested nearly $350 million in France over the past 15 years and today employs 1,100 employees at the site. The planned expansion is estimated to create around 250 new jobs once the facilities are fully operational within three to four years.
Also, in March, the company began construction of a new mega $1.8 billion production facility in Clayton, NC, that will produce active pharmaceutical ingredients (API) for a range of the company's current and future GLP-1 and insulin products. When fully operational in 2020, the site will take on production capacity for diabetes care products in the U.S. Once complete, the new facility will measure 833,000 square feet and have a footprint of 417,639 square feet--the equivalent to approximately seven football fields.
The new site is situated adjacent to Novo Nordisk's current 457,000 square foot facility. Expanded several times since it was inaugurated in 1996, Novo Nordisk's current plant in Clayton is one of the company's strategic production sites responsible for formulation, filling and packaging of diabetes medicines. The plant also assembles and packages the company's FlexPen and FlexTouch prefilled insulin devices for the U.S. market.
Once the new site becomes operational, the diabetes API production organization in Clayton will be named DAPI-US (Diabetes Active Pharmaceutical Ingredients-US). It will be part of the Danish diabetes API production organization in Kalundborg, which will be named DAPI-Denmark.
Back in August 2015, Novo Nordisk laid out plans to invest $2 billion into production facilities in Clayton; Malov, Denmark; and Kalundborg, Denmark, with $1.8 billion of this amount being invested in the Clayton plant. That same day, the company announced a decision to initiate Phase III development of oral semaglutide, a GLP-1 analogue formulated as a once-daily tablet for the treatment of type 2 diabetes.
18 MERCK KGAA
Headquarters: Darmstadt, Germany
HEADCOUNT: 50,000 YEAR ESTABLISHED: 1668 REVENUES: $15,828 (+13%) NET INCOME: $1,716 (+41%) R&D: $2,081 (+11%) DRUGS APPROVED DRUG INDICATION Bavencio bladder cancer, metastatic merkel cell carcinoma DRUGS PENDING DRUG INDICATION Cladribine tablets relapsing-remitting multiple sclerosis Avelumab metastatic urothelial carcinoma PHASE IIB AND BEYOND DRUG INDICATION Avelumab non-small cell lung cancer, 1 st, 2nd line, gastric cancer, 1 st, 3rd line, ovarian cancer, renal cell cancer, locally advanced head and neck cancer MSB 11022 chronic plaque psoriasis, biosimilar to adalimumab EARLY RESEARCH PROJECTS DRUG INDICATION M2698 solid tumors M3814 solid tumors Avelumab hematological malignancies M2951 systemic lupus erythematosus M1095 psoriasis TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Rebif multiple sclerosis $1,834 -7% Erbitux oncology $927 -6% Gonal-f fertility $793 6% Concor cardiovascular disease $454 -10% Glucophage type 2 diabetes $409 -14% Euthyrox hormone therapy $350 3%
In Merck KGaA's Healthcare division, it discovers, develops and manufactures prescription medicines used to treat cancer, multiple sclerosis, and infertility, among other things, as well as over-the-counter pharmaceutical products for colds and pain.
The Healthcare business sector comprises four businesses: Biopharma, Consumer Health, Biosimilars, and Allergopharma. In 2016, Healthcare generated 45% of group sales, or $15.8 billion. Europe and North America generated 60% of Healthcare's sales in 2016, while in recent years the company has steadily expanded its presence in growth markets. In 2016, Asia-Pacific and Latin America accounted for 33% of sales.
Biopharma is the largest of the Healthcare businesses and operates in four franchises. During the year, new data on Rebif, Biopharma's top-selling drug and leading multiple sclerosis (MS) therapy were presented at both the American Academy of Neurology's (AAN) Annual Meeting in April 2016 and the Congress of the European Academy of Neurology (EAN) in May 2016.
In June 2016, the company reached a major regulatory milestone with the submission for registration of cladribine tablets to the European Medicines Agency (EMA). The company says that cladribine tablets, if approved, could lead to high and sustained efficacy through selective modulation of B and T cells resulting in lasting resolution of inflammation.
Erbitux (cetuximab) remains the second best-selling drug in the portfolio of the Biopharma business and is the company's flagship product in oncology. In April 2016 Merck reached a major milestone regarding its expansion in growth markets with the positive results of the pivotal Chinese Phase III TAILOR study.
Also, through a strategic alliance with Pfizer, the company continued to make progress in the development and envisaged commercialization of avelumab, an investigational fully human anti-programmed death-ligand 1 (PD-L1) antibody.
The positive results from JAVELIN Merkel 200, the pivotal Phase II study in patients with metastatic Merkel cell carcinoma (MCC) treated with avelumab in second or subsequent lines of therapy, were presented at the American Society of Clinical Oncology (ASCO) 2016 annual meeting.
In terms of facility expansions, Merck KGaA continued to invest in its manufacturing network across the globe. In 2016, it completed the construction of a new facility in Nantong, China and expanded a plant in Rio de Janeiro, Brazil, as well.
The company also unveiled plans to invest more than 50 million [euro] in a new packaging center of excellence at its pharmaceutical manufacturing site in Darmstadt while also completing the expansion of its plant in Tres Cantos, Spain. In Aubonne, Switzerland, it pushed forward with the construction of a new packaging center there as well.
In the U.S., the company revealed plans for a new $115 million hub in Burlington, MA, that will serve as a major center of operations for the North American Life Science business. The new campus will also house an M Lab Collaboration Center.
Headquarters: Osaka, Japan
HEADCOUNT: 29,900 YEAR ESTABLISHED: 1781 REVENUES: $15,565 (-3%) NET INCOME: $1,038 (+40%) R&D: $2,806 (-9%) DRUGS APPROVED DRUG INDICATION Alunbrig ALK+ metastatic non-small cell lung cancer Ninlaro relapsed/refractory multiple myeloma Adcetris consolidation treatment in post-transplant Hodgkin lymphoma DRUGS PENDING DRUG INDICATION Entyvio PSC, GvHD, IO colitis Takecab PPI partial responder Rasagiline Parkinson's Cabozantinib solid tumors PHASE MB AND BEYOND DRUG INDICATION CX601 perianal fistulas in CD AD-4833 delay of MCI TAK-003 Dengue vaccine Relugolix uterine fibroids, endometriosis, prostate cancer EARLY RESEARCH PROJECTS DRUG INDICATION TAK-202 solid tumors TAK-659 hematologic malignancies TAK-788 NSCLC TAK-831 schizophrenia, ataxia TAK-935 epilepsy TAK-079 rheumatoid arthritis DRUGS COMING OFF PATENT DRUG INDICATION YEAR Actoplus MET XR type 2 diabetes 2018 Prevacid GERD 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Entyvio ulcerative colitis, $1,287 66% Crohn's disease Velcade multiple myeloma $1,237 -15% Leuprorelin prostate cancer, breast $1,026 -8% cancer, endometriosis Pantoprazole peptic ulcer $667 -26% Azilva hypertension $601 13% Dexilant acid reflux $563 -16% Alogliptin diabetes $441 0% Uloric gout and hyperuricemia $379 -1% Colcrys gout $350 -16% Takecab Acid-related diseases $306 307%
In the U.S. Takeda launched a new strategy in 2016. The goal is to refocus efforts based on recent product launches in inflammatory bowel disease (IBD) and major depressive disorder (MDD), including the creation of business units to support efforts in these areas. As part of this strategy, Takeda transferred the rights to develop and commercialize Contrave (naltrexone HCl/bupropion HCl) in the U.S. back to Orexigen, allowing the company to focus resources in areas such as MDD, IBD, gout and diabetes.
Following the launch of Entyvio (vedolizumab) in the U.S., Takeda created a dedicated Specialty business unit and acquired a U.S.-based biologics manufacturing facility for the manufacture of Entyvio and other biologics. Takeda also created a General Medicine business unit to support operations and marketing of the company's medicines in the areas of central nervous system (CNS), gastroenterology, gout and diabetes.
The new U.S. strategy and reorganization comes under the leadership of Takeda president Ramona Sequeira, who was appointed president in June 2015.
In its home base of Japan, Takeda formed a new business venture with Teva called Teva Takeda Yakuhin Ltd. Mr. Hiroshi Matsumori has been appointed chief executive officer and president of Teva Pharma Japan Inc. Takeda, an R&D driven pharma company, and Teva, a global generics company, will work to meet the needs of patients and growing importance of generics in Japan through the provision of off-patent drugs.
On the R&D front, Takeda unveiled plans for a new 100 million [euro] manufacturing plant in Singen, Germany, to support its global vaccine strategy and Phase III dengue vaccine candidate. In September, Takeda initiated the Tetravalent Immunization against Dengue Efficacy Study (TIDES), a Phase III double-blind, randomized, placebo-controlled trial, evaluating the efficacy of the vaccine candidate to protect against dengue fever. The study is also evaluating vaccine safety and immunogenicity with two doses of the vaccine candidate or placebo.
Headquarters: Dublin, Ireland
HEADCOUNT: 16,700 YEAR ESTABLISHED: 2015 REVENUES: $14,571 (+15%) NET INCOME: $14,695 (+275%) * R&D: $2,576 (+9%) * includes income from discontinued operations DRUGS APPROVED DRUG INDICATION Juvederm Volbella XC moderate to severe facial wrinkles and folds Avycaz complicated urinary tract infections Linzess chronic idiopathic constipation Rhofade persistent facial erythema DRUGS PENDING DRUG INDICATION Vraylar maintenance treatment of schizophrenia PHASE IIB AND BEYOND DRUG INDICATION Brazikumab moderate-to-severe Crohn's disease ulipristal acetate uterine fibroids Linaclotide abdominal pain in non-constipation sub-types of IBS AGN-195263 dry eye syndromes Ubrogepant migraine, with or without aura EARLY RESEARCH PROJECTS DRUG INDICATION Abicipar pegol macular degeneration DRUGS COMING OFF PATENT DRUG INDICATION YEAR Pylera stomach ulcers 2018 Delzicol Crohn's disease 2020 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Restasis dry eye $1,488 42% Botox chronic migraine, $1,189 44% Therapeutics overactive bladder Linzess/Constella irritable bowel syndrome $643 40% Bystolic hypertension $641 -1% Namenda XR Alzheimer's disease $628 -17% Alphagan/ glaucoma, $546 33% Combigan ocular hypertension Asacol/Delzicol ulcerative colitis $415 -30% Lo Loestrin contraception $404 15% Lumigan ocular hypertension $326 25%
After selling off its generics business to Teva last year for roughly $40 billion, Allergan was active on the acquisition front in 2016, picking up a handful of biotechs to bolster its pipeline. In April it acquired Topokine Therapeutics, a clinical-stage biotech focused on topical medicines for fat reduction, for $85 million upfront, gaining XAF5, a topical agent in late-stage development for the treatment of steatoblepharon (undereye bags).
In September it inked a deal to buy Vitae Pharmaceutical for $639 million, strengthening its dermatology pipeline with the addition of VTP-43742, a Phase II orally active ROR[gamma]t (retinoic acid receptor-related orphan receptor gamma) inhibitor for the potential treatment of psoriasis and other autoimmune disorders.
In the same month, Allergan bought Tobira Pharmaceuticals, a clinical-stage biopharma company developing therapies for nonalcoholic steatohepatitis (NASH) and other liver disease, for up to $1.7 billion if certain milestones are met. The acquisition adds Cenicriviroc (CVC) and Evogliptin, two development programs for the treatment of the multi-factorial elements of NASH, including inflammation, metabolic syndromes and fibrosis.
In November Allergan paid $125 million for Chase Pharmaceuticals Corp., another clinical-stage biotech developing treatments for neurodegenerative disorders including Alzheimer's disease (AD). The deal expands Allergans central nervous system (CNS) pipeline with a Phase III-ready AD candidate--Chase's lead compound, CPC-201, and certain backup compounds.
During the year Allergan entered several licensing agreements. One was with MedImmune, AstraZeneca's global biologics R&D arm, for the global rights to MEDI2070, an anti-IL-23 monoclonal antibody currently in Phase II development for the treatment of moderate-to-severe Crohn's disease and ulcerative colitis and other related conditions. Allergan paid $250 million upfront with potential payments of as much as $1.3 billion in milestones.
With Adamis Pharmaceuticals, Allergan entered into a licensing agreement with through its wholly owned subsidiary, Watson Laboratories, to commercialize Adamis'Epinephrine Pre-filled Syringe (PFS) product candidate for the emergency treatment of anaphylaxis. Watson obtains commercial rights for the U.S. in exchange for an upfront fee and potential regulatory and performance based milestones totaling up to $32.5 million. Additionally, Watson will pay royalties based on future sales of the PFS in the U.S.
In emerging markets, Allergan, again through Watson Labs, inked a $106 million generic oncology deal with China's CSPC Pharmaceutical Group relating to the product technology licensing and commercialization of an oncology drug in the global market.
Headquarters: Cambridge, MA
HEADCOUNT: 7,400 YEAR ESTABLISHED: 2003 REVENUES: $11,449 (+6%) NET INCOME: $3,703 (+4%) R&D: $1,973 (-2%) DRUGS APPROVED DRUG INDICATION Spinraza spinal muscular atrophy Fampyra improvement of walking in MS Flixabi infliximab biosimilar to Remicade DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION Aducanumab Alzheimer's disease E2609 Alzheimer's disease Obinutuzumab non-Hodgkin's lymphoma EARLY RESEARCH PROJECTS DRUG INDICATION BIIB054 Parkinson's disease BIIB067 SOD-1-amyotrophic lateral sclerosis DRUGS COMING OFF PATENT DRUG INDICATION YEAR Tysabri multiple sclerosis 2017-2020 Tecfidera multiple sclerosis 2018 TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Tecfidera multiple sclerosis $3,968 9% Avonex multiple sclerosis $2,314 -12% Tysabri multiple sclerosis $1,964 4% Eloctate hemophilia $513 61% Plegridy multiple sclerosis $482 42%
Coming off a year that ended well for Biogen, rumors of a merger with Sanofi arose following the appointment Michel Vounatsos as its new chief executive officer on December 19, and the approval of Spinraza, a potential blockbuster to treat spinal muscular atrophy, on December 23. A Sanofi-Biogen deal would create a 60% stronghold in the oral MS market.
Spinraza, which was developed by Ionis Pharmaceuticals and licensed by Biogen, was approved under Priority Review by the FDA and is the first treatment for spinal muscular atrophy in pediatric and adult patients. Analysts estimate that Spinraza could generate revenues of as much as $428 million in 2017, with sales potentially reaching $2 billion by 2020.
Also in December, Biogen presented positive data from the Phase lb PRIME study, showing its investigational drug aducanumab slows cognitive decline in patients in the early stages of Alzheimer's disease, while reducing the amyloid plaque levels compared to the placebo group.
Aducanumab is currently being evaluated in two global Phase III studies, ENGAGE and EMERGE, which are designed to evaluate its safety and efficacy in slowing cognitive impairment and the progression of disability in early AD. The success of this drug would add billions in annual sales to Biogen's top line, but that's counting chickens before they hatch.
Moreover, Biogen recently paid Bristol Myers-Squibb $300 million upfront, plus as much as $410 million for milestones and potential royalties, for BMS-986168, a Phase II-ready antibody targeting extracellular tau, the protein that forms the deposits in the brain associated with Alzheimer's Disease and other neurodegenerative tauopathies such as Progressive Supranuclear Palsy. Biogen plans to rapidly initiate Phase II studies for BMS-986168 in both indications.
In another asset acquisition, Biogen acquired Remedy Pharmaceuticals' Phase III candidate, CIRARA for the potential treatment of large hemispheric infarction, a severe form of ischemic stroke where brain swelling often leads to stroke-related morbidity and mortality. The FDA recently granted CIRARA Orphan Drug status, along with Fast Track designation.
Meanwhile, in the multiple sclerosis space, revenue from Biogen's top-selling drug, Tecfidera, reached nearly $4.0 billion, up 9%. Even though there was a slight softening in overall market, particularly in the U.S., the European market continues to grow, albeit at a slower pace.
Equally significant, Fampyra was granted marketing authorization in the EU. As the first treatment to address both the unmet need of walking improvement in MS, as well as clinical efficacy in MS, it has potential to substantially impact this market. Biogen has a license from Acorda Therapeutics for rights in all markets outside the U.S.
In the way of strategic business ventures, Bioverativ, the spinoff of Biogen's global hemophilia business, began trading January 2017. Sales of its hemophilia drugs, Eloctate and Alprolix generated combined revenues of $847 million in 2016, up 53%.
Biogen's pipeline aims to address some of the greatest challenges in medicine, including Alzheimer's disease, Parkinson's, and ALS, let's hope they succeed. We'll have to see about Biogen becoming a potential takeover target.
Headquarters: Lexington, MA
HEADCOUNT: 23,906 YEAR ESTABLISHED: 1986 REVENUES: $11,397 (+78%) NET INCOME: $327 (-75%) R&D: $1,440 (-8%) DRUGS APPROVED DRUG INDICATION Cuvitru primary immunodeficiency Xiidra dry eye disease Glassia emphysema due to severe AAT deficiency Intuniv ADHD Ady novate hemophilia A children and surgical settings ONIVYDE with 5-FU metastatic adenocarcinoma of the pancreas and leucovorin DRUGS PENDING DRUG INDICATION Natpar hypoparathroidism SHP465 ADHD DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION Glassia acute graft vs. host disease Calaspargase pegol acute lymphoblastic leukemia Cinryze antibody mediated rejection Gattex short bowel syndrome SHP555 chronic constipation SHP620 cytomegalovirus infection Vonvendi Von Willebrand disease EARLY RESEARCH PROJECTS DRUG INDICATION SHP611 MLD SHP622 Friedreich's ataxia SHP 623 neuromyelitis optica SHP631 neurocognitive decline associated with Hunter syndrome SHP655 hereditary thrombotic thrombocytopenic purpura SHP656 hemophilia A TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Vyvanse ADHD $2,014 17% Hemophilia hematology $1,789 n/a Immunoglobulin immunology $1,144 n/a Therapies Lialda ulcerative colitis $792 16% Cinryze hereditary angioedema $680 10% Elaprase Hunter syndrome $589 7%
At the beginning of 2016, Irish drug maker Shire catapulted itself into the top 25 companies after it bought American pharma firm Baxalta. The $32 billion mega-deal creates a global biotech projected to generate over $20 billion in annual revenues by 2020.
The combination of the two pharmaceutical giants creates a world leader in rare diseases, a platform for which Shire will now have leading products in each of the following growing, multi-billion-dollar therapeutic areas: hematology; immunology; neuroscience; lysosomal storage diseases; gastrointestinal/endocrine; and hereditary angioedema (HAE).
The combined company will also have a growing franchise in oncology, with approved products and innovative compounds in development, as well as a robust late-stage ophthalmics pipeline.
Altogether, there will be more than 60 programs in development, including over 50 that will address rare diseases, and the newly-approved Baxalta products Adynovate,Vonvendi and Obizur. Shire anticipates more than 30 recent and planned product launches from the combined pipeline, contributing approximately $5 billion in annual revenues by 2020.
On the heels of the deal, towards the end of the year, Shire unveiled plans to expand its operations in Cambridge, MA, establishing a rare disease innovation hub and increasing its footprint in Kendall Square, leasing a 343,000-sq.-ft. building with occupancy anticipated for the first quarter of 2019.
Shire will create a cross-disciplinary campus with teams spanning research, clinical development, medical affairs, business development, and other related functions. It will retain its current office, lab, and manufacturing space in Mass., including its presence in Lexington, where it's been located since 2007. Shire currently employs more than 3,000 people in the state and as part of its growth in Kendall Square, Shire is undertaking a strategic review to identify which specific functions will be located there over time and plans to add nearly 400 positions.
At the tail end of the year, Shire U.S. Manufacturing entered into a multi-year supply agreement for an undisclosed product with AMRI. The product has been in AMRI's portfolio through the required stages of development. This is the second such multi-year agreement between AMRI and Shire, as AMRI has also been supplying a neuroscience product to Shire.
Headquarters: Summit, NJ
HEADCOUNT: 7,000 YEAR ESTABLISHED: 1986 REVENUES: $11,229 (+21%) NET INCOME: $1,999 (+25%) R&D: $4,470 (+21%) DRUGS APPROVED DRUG INDICATION Revlimid monotherapy for the maintenance treatment of multiple myeloma, multiple myeloma in hematopoietic stem cell transplant, relapsed/refractory mantle cell lymphoma DRUGS PENDING DRUG INDICATION Enasidenib acute myeloid leukemia DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION CC-486 myelodysplastic syndrome Luspatercept myelodysplastic syndrome, beta-thalassemia Revlimid follicular lymphoma: first-line, indolent lymphoma: relapsed/refractory Otezla ankylosing spondylitis Ozanimod relapsing multiple sclerosis, ulcerative colitis Mongersen Crohn's disease EARLY RESEARCH PROJECTS DRUG INDICATION durvalumab multiple myeloma, acute myeloid leukemia CC-122 multiple myeloma, relapsed/refractory lymphoma, chronic lymphocytic leukemia CC-90002 myelodysplastic syndrome, acute myeloid leukemia, solid tumors AG-881 acute myeloid leukemia CC-90009 acute myeloid leukemia romidepsin diffuse large B-cell lymphoma CC-90001 fibrosis CC-90006 autoimmune disorders PNK-007 multiple myeloma cell therapy TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Revlimid multiple myeloma, $6,974 20% mantle cell lymphoma Pomalyst multiple myeloma $1,311 33% Otezla psoriasis $1,017 116% Abraxane breast, lung, $973 1% pancreatic cancer Vidaza myelodysplastic syndrome $608 3%
Coming off a successful 2016, results for 1Q17 were equally impressive, with revenues up 18% to nearly $3.0 billion. Celgene's three top-selling drugs, Revlimid, Pomalyst and Otezla, climbed 20%, 33%, and 24%, respectively. The new year also began with positive Phase II data of ozanimod in Crohn's disease and Phase III trials planned by year-end. Ozanimod, an immunomodulatory drug, is also in Phase III trials in relapsing multiple sclerosis (RMS), which met the primary endpoint in reducing relapse rate compared to weekly interferon (Avonex), and demonstrated significant reductions in brain atrophy compared to Avonex. An NDA to the FDA, based on the trials for RMS, is expected by the end of this year.
In other R&D news, Celgene's NDA for enasidenib in relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation was granted Priority Review and given a Prescription Drug User Fee Act (PDUFA) action date of Aug. 30,2017. Also, the FDA approved an expanded indication for Revlimid as a maintenance treatment for multiple myeloma following autologous hematopoietic stem cell transplant, making it the first and only treatment to receive FDA approval for maintenance following auto-HSCT.
When it comes to alliances, Celgene is known for its costly pursuit of drug development partnerships, which has thus far led to a diverse pipeline appealing assets. At the start of this year, Celgene acquired Delinia, Inc. for $300 million upfront and as much as additional $475 million, expanding its pipeline of potential next-gen medicines for autoimmune disorders. The transaction expands Celgene's inflammation and immunology pipeline with Delinia's lead program, DEL106, as well as related programs with potential to treat systemic lupus erythematosus and rheumatoid arthritis.
Entering the immunotherapy race, a global immuno-oncology alliance with BeiGene aims to advance a PD-1 inhibitor program for solid tumor cancers. This set Celgene back $263 million and a $150 million equity investment. The deal complements Celgene's partnership with AstraZeneca to develop durvalumab in hematological malignancies and expand its presence in China's cancer market.
Other recent deals include a TriNKET platform pact with Dragonfly to develop natural killer cell-based immunotherapies. Celgene has the exclusive option to license as many as four candidates with potential to treat acute myeloid leukemia, multiple myeloma, and additional hematological malignancies.
Headquarters: Canonsburg, PA
HEADCOUNT 35,000 YEAR ESTABLISHED 1970 REVENUES: $11,077 (+18%) SPECIALTY SEGMENT: $5,630 (+10%) NET INCOME: $480 (-43%) R&D: $827 (+23%)
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 most prescribed autoinjector with over 90% market share in the U.S. and worldwide.
DRUGS PENDING DRUG INDICATION proposed biosimilar neutropenia of pegfilgrastim proposed biosimilar breast cancer of trastuzumab insulin glargine type 2 diabetes EARLY RESEARCH PROJECTS DRUG INDICATION proposed biosimilar rheumatoid arthritis to abatacept DRUGS IN PHASE IIB AND BEYOND DRUG INDICATION revefenacin chronic obstructive pulmonary disease
During 2016 the generic giant Mylan made two major acquisitions. First it boosted its over-the-counter (OTC) portfolio when it paid nearly $10 billion for Swedish drug maker Meda, adding a range of branded and generic pharmaceuticals. Meda's key products include the allergy therapy Dymista (azelastine/fluticasone) and Elidel (pimecrolimus) for dermatitis and eczema. The deal reduces Mylan's reliance on generic drugs with the addition of specialty brands that are less prone to pricing pressure and competition.
In another deal worth $1 billion, Mylan bought the non-sterile, topicals-focused specialty and generics business of Renaissance Acquisition Holdings, which nets Mylan a complementary portfolio of approximately 25 branded and generic topical products, a pipeline of approximately 25 products, and an established U.S. sales and marketing infrastructure targeting dermatologists. The business also brings Mylan an integrated manufacturing and development platform and a topicals-focused contract development and manufacturing organization.
The dermatology/topicals space has long been an area of focus for Mylan and one that it has targeted for expansion. Renaissance had approximately $370 million in 2015 revenues and has approximately 1,200 employees. The business's commercial segment has a diversified portfolio of specialty brands and generic products in the dermatology space, as well as a pipeline of complex topical generics and brands in active development. Also, the acquisition includes two manufacturing sites with capabilities and capacity in creams, ointments, aerosols/foams, gels, suspensions, liquids and suppositories.
Mylan was also active on the biosimilar front during the year. In a deal worth up to $250 million, it entered into an exclusive global collaboration agreement with Momenta Pharmaceuticals to develop and commercialize six of Momenta's biosimilar candidates, including abatacept--Bristol-Myers Squibb's rheumatoid arthritis drug Orencia. The companies are jointly responsible for product development, and Mylan will lead worldwide commercialization. The collaboration builds on Mylan's existing biologics 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 submitted three biosimilar applications and one insulin application in the U.S. and EU in 2016.
On the new product front, Mylan made several generic advances during the year. Following FDA approval it launched Azacitidine injection, a generic of Celgene's (CELG) Vidaza injection. It also launched Propafenone Hydrochloride extended-release capsules, the generic of GlaxoSmithKline's Rythmol capsules. The company then launched Hydralazine Hydrochloride injections, a generic version of Novartis's Apresoline injection.
Mylan currently has over 250 abbreviated new drug applications (or ANDAs) pending FDA approval. A few other recent launches include: Clindamycin Palmitate Hydrochloride, a generic version of Cleocin solution; Doxycycline Hyclate delayed-release tablets, a generic version of Doxteric; Armodafinil tablets, a generic version of Nuvigil; and Frovatriptan Succinate tablets, a generic version of Frova tablets. The FDA has also accepted its ANDA for fluticasone propionate and Salmeterol, a generic version of GlaxoSmithKline's Advair Diskus, with a GDUFA date of March 28,2017.
Headquarters: Tokyo, Japan
HEADCOUNT: 11,238 YEAR ESTABLISHED: 1921 REVENUES: $10,240 (-16%) NET INCOME: $866 (-32%) R&D: $1,446 (-17%) DRUGS APPROVED DRUG INDICATION Rexulti schizophrenia Abilify irritability in pediatric autism spectrum disorder Mikeluna glaucoma and ocular hypertension DRUGS PENDING DRUG INDICATION Samsca/JINARC hepatic edema, cardiac edema Abilify Maintena bipolar I / depot injection Zosyn complicated skin, soft tissue infections PHASE IIB AND BEYOND DRUG INDICATION Rexulti major depressive disorder / oral, agitation associated with dementia ASC-01 major depressive disorder AVP-786 agitation associated with dementia Lu AA36143 alcohol dependence Lonsurf colorectal cancer, gastric cancer TAS-118 pancreatic cancer, gastric cancer SGI-110 acute myeloid leukemia, myelodysplastic syndrome Samsca/Jinarc autosomal dominant polycystic kidney disease AKB-6548 anemia associated with chronic kidney disease OPC-12759E dry eyes SGI-110 myelodysplastic syndrome EARLY RESEARCH PROJECTS DRUG INDICATION Rexulti schizophrenia / depot injection Lu AF20513 Alzheimer's demetia / injection ASTX660 solid tumors, lymphomas OPB-111077 solid tumors TAS-117 solid tumors TAS-119 solid tumors TAS3681 prostate cancer QCV-C02 colorectal cancer TOP SELLING DRUGS DRUG INDICATION 2016 SALES (+/-%) Abilify schizophrenia $817 -72% Samsca/Jinarc hyponatremia $419 18% Abilify Maintena schizophrenia $490 41%
The pharmaceutical business of The Otsuka Group focuses on the priority areas of the central nervous system and oncology. To support global expansion efforts, Otsuka recently announced plans to construct a new pharmaceutical manufacturing facility in Mima City, Japan, which is scheduled to begin operations in 2020. Otsuka currently manufactures pharmaceuticals and ingredients at five factories in Japan.
Also, the recent acquisition of Neurovance, Inc. expands Otsuka's attention-deficit hyperactivity disorder (ADHD) strategy in the CNS therapy area to develop new products that also address issues of patient compliance and the challenging side effects from existing medications. Neurovance is developing centanafadine, a non-stimulant, triple reuptake inhibitor in patients with ADHD, and it has shown comparable efficacy to stimulant drugs with a potentially lower risk of abuse.
The company's antipsychotic drug Ability gained approval in Japan for the additional indication of irritability in pediatric autism spectrum disorder. This is the fourth indication for Otsuka's top seller, after schizophrenia, bipolar I disorder, and depression.
Under its alliance with development partner Lundbeck, Health Canada approved REXULTI for the treatment of schizophrenia. REXULTI, which became commercially available in Canada this spring, was discovered by Otsuka and will be co-marketed by the two companies. Separately, the U.S. FDA approved a labeling update of REXULTI for maintenance treatment of schizophrenia.
Otsuka and Lundbeck also recently announced positive results from Phase III trials evaluating brexpiprazole in the treatment of agitation in dementia of the Alzheimer's type, which showed improvements in symptoms relative to placebo.
Additionally, results from the companies Phase III trials of nalmefene in alcohol dependency demonstrated a statistically significant difference compared to placebo for the primary endpoint. This candidate is anticipated as a new, potentially continuous treatment option for the purpose of reducing alcohol consumption and social reintegration.
Among its late stage assets, Otsuka and Proteus Digital Heath have resubmitted an application to the FDA for the first potential digital medicine, which consists of Abilify embedded with the Proteus ingestible sensor in a single tablet, intended for serious mental illness. If approved, the drug/device would provide digital records of medication ingestion and share information with healthcare providers. The NDA has an anticipated action date in 4Q17.
Caption: The headquarters of pharmaceutical giant Pfizer in Manhattan, New York. With $52.8 billion in 2016 revenue, Pfizer again is the top (bio)pharma company in the world.
Caption: Novartis headquarters in Basel. Switzerland. The Swiss multinational pharmaceutical company ranks number two in Big Pharma sales in 2016 with $48.5 billion of revenues.
Caption: Sales of Merck's cancer drug Keytruda grew 150% in 2016 to $1.4 billion.
Caption: Roche's $6.6 billion cancer drug Herceptin grew 1 % during the year while arthritis drug RoActerma reached $1.6 billion in sales on 15% growth.
Caption: Roche headquarters in Basel, Switzerland. With $38.4 billion in sales, Roche is the fourth largest drug maker in the world.
Caption: UK-based GSK moved into the top five with nearly $38 billion in drug sales for 2016.
Caption: J&J's headquarters in New Brunswick, NJ. A 24% increase in oncology sales helped boost revenues to $33.5 billion for the year.
Caption: AbbVie's HQ in Chicago, IL. The maker of blockbuster Humira delivered its strongest year yet since launching four years ago.
Caption: Dave Ricks
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|Date:||Jul 1, 2017|
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