TOP 25 COMPANIES AND BIOPHARMA REPORT.
Headquarters: New York, NY
HEADCOUNT: 92,400 YEAR ESTABLISHED: 1849 REVENUES: $53,647 (+2%) NET INCOME: $11,153 (-48%) R&D: $8,006 (+4%)
DRUGS APPROVED DRUG INDICATION Retacrit Anaemia in chronic kidney disease (CKD) (dialysis) Lorbrena Non-small cell lung cancer (NSCLC) Vizimpro Non-small cell lung cancer (NSCLC) Talzenna Breast cancer Daurismo Leukaemia, acute myeloid (AML) Seizalam Generalised seizures Doxercalciferol Hyperparathyroidism DRUGS FILED DRUG INDICATION NuThrax Anthrax prophylaxis Daptomycin Skin infections QUZYTTIR Urticaria PHASE III DRUG INDICATION PF-04965842 Eczema/Dermatitis PF-06425090 Clostridium difficile-associated diarrhoea (CDAD) Lagova Short stature in children, Adult growth hormone deficiency Rivipansel Sickle cell disease PF-06651600 Alopecia/Male pattern baldness Tanezumab Pain, lower back, Pain, cancer-induced, Osteoarthritis PF-06482077 Pneumococcal infection prophylaxis Fidanacogene Elaparvovec Haemophilia B ATM-AVI Gram negative infections, Pneumonia Tremelimumab Non-small cell lung cancer (NSCLC), Head & Neck cancer, Bladder cancer, Liver cancer, Small cell lung cancer (SCLC) Crenolanib Gastro-intestinal stromal tumours (GIST) Sulopenem Oral Prodrug General bacterial indications, Urinary tract infections (UTIs) SHP647 Ulcerative colitis, Crohn's disease Sulopenem IV General bacterial indications Maralixibat Cholestasis S/GSK1265744 LAP HIV treatment PF-06741086 Haemophilia A AN5568/ SCYX-7158 i Trypanosomiasis PF-05416266 Sickle cell disease TPOXX Smallpox treatment EARLY RESEARCH PROJECTS DRUG INDICATION PF-06753512 Prostate Cancer PF-06760805 Invasive Group B streptococcus infection PF-06886992 Serogroups ABCWY meningococcal infections PF-06928316 Respiratory Syncytial Virus Infection PF-06936308 Multiple Cancers PF-06647020 Biologic Cancer PF-06801591 Biologic Cancer Immunotherapy PF-06821497 Cancer PF-06863135 Biologic Multiple Myeloma PF-06873600 Metastatic Breast Cancer PF-06939999 Solid Tumors PF-06952229 Cancer PF-04518600 Biologic Cancer PF-06763809 Psoriasis PF-06817024 Biologic Atopic Dermatitis PF-06826647 Inflammatory Bowel Disease PF-06835375 Biologic Lupus PF-06939926 Biologic Duchenne Muscular Dystrophy PF-04447943 Sickle Cell Anemia PF-06865571 Non-alcoholic Steatohepatitis PF-06882961 Diabetes Mellitus- Type 2
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Lyrica epilepsy, neuropathy 2019 Chantix smoking cessation 2020 Sutent cancer 2021
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Prevnar 13 pneumoccal vaccine $5,802 4% Lyrica epilepsy, neuropathy $4,970 -2% Ibrance cancer $4,118 32% Enbrel rheumatoid arthritis $2,112 -14 Lipitor cholesterol $2,062 8% Xeljanz arthritis $1,774 32% Chantix smoking cessation $1,085 9% Sutent cancer $1,049 -3% Norvasc hypertention $1,024 11% Premarin menopause $832 -15%
In 2018, Pfizer reported revenues of $53,647 billion, an increase of two percent, as several of its biggest-selling medicines and vaccines continued to grow, including Ibrance, Eliquis, Xeljanz and Prevnar 13. Pfizer also reported growth in emerging markets and in bio-similars, which helped to absorb $1.7 billion in lost revenue because of products that recently lost marketing exclusivity. Eight billion dollars was invested during the year in research and development (R&D).
During the year, Pfizer unveiled plans to reorganize into three businesses, which became effective at the beginning of the company's 2019 fiscal year, and are Pfizer Biopharmaceuticals Group, that now includes biosimilars and a new Hospital business unit for anti-infectives and sterile injectables; Upjohn, an off-patent branded and generic medicines business based in China that is bringing 20 of its most iconic brands to more than 100 markets around the world; and a Consumer Healthcare business aligned with the growing trend of consumers taking their health into their own hands.
Also on the consumer side of the business, at the end of the year Pfizer and GlaxoSmithKline entered a joint venture to create a global consumer healthcare company. The deal calls for Pfizer contributing its consumer healthcare business to GlaxoSmithKline's existing consumer healthcare business. The 2017 global sales for the combined business were approximately $12.7 billion. The deal is expected to close in the second half of 2019.
The joint venture will be a category leader in pain relief, respiratory, vitamin and mineral supplements, digestive health, skin health and therapeutic oral health. It's expected to be among the largest consumer healthcare players in key geographies, including the U.S., Europe, China, India and Australasia. The joint venture will operate globally under the GSK Consumer Healthcare name. Following the integration, GSK intends to separate the joint venture as an independent company.
As we moved into 2019, it was announced that Dr. Albert Bourla, chief operating officer at the time, would be taking over the reins of the stripped down Pfizer organization as its new chief executive officer, succeeding Ian Read. Under Mr. Read, Pfizer received 30 FDA approvals and amassed a pipeline with the potential for approximately 25-30 approvals through 2022, of which as many as 15 have the potential to be blockbusters.
STERILE MANUFACTURING INVESTMENT
In terms of growth, Pfizer is investing $465 million to expand its U.S. manufacturing with technically advanced sterile in-jectable pharmaceutical production facilities in Portage, MI, which will create approximately 450 new jobs over the next several years. Known as Modular Aseptic Processing (MAP), the new 400,000 square foot production facility expands Pfizer's presence in Portage, located in Kalamazoo County, where the company now employs more than 2,200 people at one of its largest plants.
MAP will incorporate technically advanced aseptic manufacturing equipment, systems and design, including multiple, self-contained modular manufacturing lines. This allows the manufacturing line in each module to be entirely separate from all other manufacturing lines. Construction is expected to be completed in 2021. After the facility is validated by regulatory agencies, production should begin in 2024.
The investment is part of Pfizer's overall plan to invest approximately $5 billion in U.S.-based capital projects as a result of the enactment of the Tax Cuts and Jobs Act. During the next six years, the company expects to invest approximately $1.1 billion in Kalamazoo County, which is in addition to the $1 billion it has invested in the site over the past decade.
The Portage site is a primary global supplier of sterile injectable, liquids and semi-solid medicines, and active pharmaceutical ingredients (APIs), producing more than 150 products. Its biggest product is Solu-Medrol, a widely used injectable anti-inflammatory medicine.
CANCER RESEARCH COLLABORATIONS
Pfizer remained active during the year on the cancer research front. It inked a deal worth up to $520 million with Kineta Immuno-Oncology (KIO), to develop RIG-I agonist immunotherapies for the treatment of cancer.
Leap Therapeutics entered into a collaboration with Pfizer and Merck KGaA to evaluate Leap's GITR agonist, TRX518, in combination with avelumab, a human anti-PD-Ll IgGl monoclonal antibody, and chemotherapy. Avelumab has received accelerated approval by the FDA for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA and Pfizer.
Daiichi Sankyo also entered into a clinical trial collaboration agreement with Pfizer and Merck KGaA to evaluate the combination of [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), in combination with the checkpoint inhibitor avelumab and/or an investigational Merck KGaA DNA damage response PDR) inhibitor, in patients with HER2 expressing or mutated solid tumors.
A separate research collaboration to conduct preclinical studies evaluating [fam-] trastuzumab deruxtecan in combination with avelumab, the DDR inhibitor and other investigational compounds in Merck KGaA's and Pfizer's pipelines is also underway.
Aside from cancer, during the year Pfizer also signed a $425 million flu vaccine deal with BioNTech AG, a biotech focused on precise immunotherapies for the treatment of cancer and infectious disease. The multi-year R&D collaboration's goal is to develop mRNA-based vaccines for the prevention of influenza (flu).
Caption: Pfizer's headquarters in Manhattan. The American multinational pharmaceutical giant is again the world's largest drug maker with nearly $54 billion in revenue.
Headquarters: Basel, Switzerland
HEADCOUNT: 125,161 YEAR ESTABLISHED: 1996 REVENUES: $51,900 (+6%) PHARMA REVENUES: $44,751 (+6%) NET INCOME: $12,614 (+64%) R&D: $9,074 (+1%)
DRUGS APPROVED DRUG INDICATION Lutathera Neuroendocrine tumor Aimovig Migraine Hyrimoz Arthritis, rheumatoid, Psoriasis, Arthritis, psoriatic, Ankylosing spondylitis, Crohn's disease, Arthritis, juvenile idiopathic (JIA), Ulcerative colitis DRUGS FILED DRUG INDICATION Pretomanid Tuberculosis (TB) Brolucizumab Wet age-related macular degeneration PHASE III DRUG INDICATION Arzerra S.C. Relapsing-Remitting MS (RRMS) QAW039 Asthma, Nasal polyp PSMA-617 Prostate cancer Capmatinib Non-small cell lung cancer (NSCLC) Crizanlizumab Sickle cell disease QMF149 Asthma ABL001 Leukaemia, chronic myeloid (CML) PDR001 Melanoma Lamprene Tuberculosis (TB) QGE031 Urticaria LMI070 Spinal muscular atrophy Onalta Neuroendocrine tumour CAD106 Alzheimer's disease TKI258 Renal cell carcinoma (RCC) Bivalent Typhoid Fever Vaccine Typhoid BGJ398 Biliary cancer QPI-1002 Kidney transplantation CDZ173 Other immune indications CNP520 Alzheimer's disease AS-2 Anaesthesia, general Nerviano/ B-RAF solid tumors EARLY RESEARCH PROJECTS DRUG INDICATION AVXS-201 Rett syndrome CFZ533 solid organ transplantation CAD106 Alzheimer's disease CNP520 Alzheimer's disease CSJ117 severe asthma ECF843 dry eye HDM201 acute myeloid lymphoma KAE609 malaria KAF156 malaria LJC242 non-alcoholic steatohepatitis LJN452 non-alcoholic steatohepatitis LMI070 spinal muscular atrophy LNP023 IgA nephropathy LOU064 chronic spontaneous urticaria MOR106 atopic dermatitis QBW251 chronic obstructive pulmonary disease SAF312 chronic ocular surface pain UNR844 presbyopia VAY736 autoimmune hepatitis VAY785 non-alcoholic steatohepatitis VPM087 colorectal cancer ZPL389 atopic dermatitis Zolgensma IV formulation spinal muscular atrophy
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Exjade iron overload 2019 Afinitor Renal cell carcinoma 2020 Galvus Diabetes, type II 2022 Lucentis Wet AMD 2022 Promacta Thrombocytopaenic purpura, idiopathic 2023 Tasigna Leukaemia, chronic 2023 myeloid
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Gilenya autoimmune disease $3,341 5% Cosentyx Psoriasis, ankylosing spondylitis and psoriatic arthritis $2,837 37% Lucentis age-related macular degeneration $2,046 8% Tasigna chronic myeloid leukemia $1,874 2% Sandostatin acromegaly $1,587 -2% Gleevec Leukaemia, chronic myeloid (CML) $1,561 -20% Afinitor oncology $1,556 2% Galvus diabetes $1,284 4% Promacta Thrombocytopaenic purpura, idiopathic (ITP) $1,174 35% Tafinlar Melanoma $1,155 32%
With pharmaceutical sales of nearly $45 billion, Novartis slid into second just ahead of Roche in this year's report--up four spots from last year's sixth place ranking. Under the leadership of new chief executive, Vasant Narshimhan, 2018 saw Novartis involved in several deals that has the Swiss pharma giant focused more on medicines.
First it inked an $8.7 billion deal to acquire gene therapy company AveXis as part of its neuroscience strategy. AveXis is conducting several clinical studies for the treatment of spinal muscular atrophy, or SMA, an inherited neurodegenerative disease caused by a defect in a single gene. Their gene therapy candidate AVXS-101 has the potential to be the first one-time gene replacement therapy for SMA according to Novartis, and it currently has orphan drug designation from the U.S. Food and Drug Administration for the treatment of SMA.
The deal followed shortly after Novartis sold its stake in its consumer health-care joint venture to GlaxoSmithKline for $13 billion. The company also decided to spin off its Alcon eye-care unit and sold parts of its Sandoz generic-drugs unit, specifically the Sandoz U.S. dermatology business and generic U.S. oral solids portfolio, to Aurobindo Pharma USA for $800 million.
The Sandoz U.S. portfolios to be sold to Aurobindo include approximately 300 products as well as additional development projects. The sale includes the Sandoz U.S. generic and branded dermatology businesses as well as its dermatology development center. As part of the transaction, Aurobindo will acquire the manufacturing facilities in Wilson, NC, and in Hicksville and Melville, NY.
In another acquisition, Novartis bought cancer-drug maker Endocyte for $2.1 billion. Endocyte is a U.S. company developing a new treatment for prostate cancer. It specializes in radiopharmaceuticals, a new class of drug that carries radioactive substances directly to cancer cells so they can kill tumor cells at close range. It uses drug conjugation technology to develop targeted therapies with companion imaging agents, including 177LuPSMA-617, a potential first-in-class investigational radioligand therapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
The prostate cancer drug bolsters its capability in the field, which it expects to be a key growth driver moving forward, and joins another late-stage radiopharmaceutical directed at a rare form of gut cancer, acquired when it bought Advanced Accelerator Applications S.A. for $3.9 billion at the end of 2017.
EXPANDING MANUFACTURING CAPACITY
At the end of 2018, Novartis announced it had made an offer for the Frerich contract development and manufacturing organization (CDMO), CellforCure, from its parent, LFB. CellforCure is one of the first and largest CDMOs producing cell and gene therapies in Europe.
The deal has subsequently closed for an undisclosed amount and includes the cell and gene manufacturing facility located in Les Ulis, France. CellforCure is now a wholly owned Novartis manufacturing site, joining the network of cell and gene therapy sites including Morris Plains, NJ in the U.S. and Stein, Switzerland, where construction continues to progress on the 79 million [euro] facility.
The deal builds on a previously signed agreement in July 2018. Novartis signed a deal with CellforCure to produce CAR-T cell therapies including Kymriah (tisagenlecleucel), the first CAR-T cell therapy approved by the U.S. Food and Drug Administration (FDA) and indicated for two distinct, difficult-to-treat cancers in the U.S., EU, Switzerland, Canada and Australia. Novartis and CellforCure have successfully completed technology transfer and Kymriah clinical supply production is expected to begin by mid-2019.
In addition to the CellforCure deal, Novartis has made several steps to strengthen and expand its cell and gene manufacturing, including signing a strategic licensing, collaboration and share purchase agreement with Cellular Biomedicine Group (CBMG) to manufacture and supply Kymriah in China; expanding an alliance with the Fraunhofer Institute in Germany to support manufacturing for clinical trials and post approval manufacturing; and a contract manufacturing collaboration in Japan.
PARTNERSHIP FOR VIRTUAL TRIALS
Novartis formed an alliance with Science 37 to initiate up to 10 new clinical trials over the next three years. The studies will blend virtual and traditional models, with increasing degrees of decentralization towards a mostly "site-less" model. Novartis was an early investor in Science 37 and together have already initiated virtual trials for cluster headache, acne and nonalcoholic steatohepatitis (NASH).
The new decentralized trials in the U.S. will focus on dermatology, neuroscience and oncology, leveraging Science 37's proprietary Network Oriented Research Assistant (NORA) technology, which enables patients to participate in studies using mobile devices and telemedicine services. Through this alliance, the companies plan to apply Science 37's customized enterprise software to some of the leading clinical development programs of Novartis.
According to the Center for Information & Study on Clinical Research Participation (CISCRP), only 2% of the eligible population in the U.S. participate in clinical trials. Those who do participate attend an average of 11 trial site visits in six months, representing a significant burden for both patients and trial centers. By bringing the trial to the patient, Novartis aims to decrease the burden of clinical trial participation on patients and trial centers.
Caption: Novartis headquarters in Basel, Switzerland. Novartis is a Swiss multinational pharmaceutical company ranking number two in Big Pharma sales in 2018.
Headquarters: Basel, Switzerland
HEADCOUNT: 94,442 TOTAL REVENUES: $57,734 (+7%) PHARMA REVENUES: $44,654 (+5%) NET INCOME: $11,035 (+23%) R&D: $12,281 (+6%)
DRUGS APPROVED DRUG INDICATION Xofluza Influenza Trogarzo HIV treatment DRUGS FILED DRUG INDICATION Entrectinib Solid tumour indications, Non-small cell lung cancer (NSCLC) PHASE III DRUG INDICATION Risdiplam Spinal muscular atrophy RG7716 Macular oedema, Wet age-related macular degeneration (AMD) RG6042 Huntington's disease Ipatasertib Prostate cancer, Breast cancer Etrolizumab Ulcerative colitis, Crohn's disease Satralizumab Neuromyelitis optica (NMO) Idasanutlin Leukaemia, acute myeloid (AML) Balovaptan Autism spectrum disorders (ASD) Gantenerumab Alzheimer's disease RG6206 Duchenne muscular dystrophy Palovarotene Bone repair & regeneration Dalcetrapib Hyperlipidaemia HZN-001 Grave's disease Gefapixant Cough/Common cold MGL-3196 Familial hypercholesterolaemia, Nonalcoholic steatohepatitis (NASH), Liver fibrosis QGE031 Urticaria Lucentis SR Wet age-related macular degeneration (AMD) HMS5552 Diabetes, type II (maturity onset) Tearexaban Thrombosis, deep vein (DVT), Pulmonary embolism RG6264 Breast cancer EARLY RESEARCH PROJECTS DRUG INDICATION CHU solid tumors RG6026 relapsed or refractory non-hodgekin's lymphoma RG6058 tiragolumab solid tumors in combination with tecentriq RG6109 acute myeloid leukemia RF6114 metastatic ER-positive and HER2-negative breast cancer RG6123 solid tumors RG6146 oncology RG6148 HER2-positive breast cancer RG6160 relapse or refractory multiple myeloma RG6171 ER-positive and HER2-negative metastatic breast cancer RG6185 solid tumors RG6194 metatatic HER2-positive cancers RG7461 solid tumors RG6107 crovalimab paroxysmal nocturnal hemoglobinuria RG7828 hematologic tumors RG6151 asthma RG6173 asthma RG7835 autoimmune diseases RG7880 inflammatory diseases RG6147 geographic atrophy RG6127 chronic hepatitis B infection RG7861 infections caused by staphylococcus aureus RG7992 metabolic diseases RG6000 amyotrophic lateral sclerosis RG6237 neuromuscular disorders
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Herceptin breast cancer 2019 Avastin cancer 2019 Lucentis macular degeneraton 2020 Esbriet Pulmonary fibrosis, idiopathic 2021
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) MabThera /Rituxan rheumatoid arthritis $6,905 -8% Herceptin cancer $7,140 0% Avastin breast cancer $7,004 3% Perjeta breast cancer $2,836 27% Ocrevus Relapsing-Remitting MS (RRMS) $2,406 173% Xolair asthma $1,986 12% Actemra/ RoActemra rheumatoid arthritis $1,847 12% Lucentis macular degeneraton $1,697 18% Activase/TNKase myocardial infarction $1,313 6% Esbriet Pulmonary fibrosis, idiopathic $1,054 19%
Roche's pharma sales grew 5% to $44.6 billion in 2018. Key growth drivers were the new multiple sclerosis medicine Ocrevus and cancer medicines Perjeta, Tecentriq, Alecensa as well as the new haemophilia medicine Hemlibra. With sales of $2.4 billion in its first full year on key markets, Ocrevus is the most successful new product launch in Roche's history.
On the regulatory front, the Swiss pharma giant received several major approvals during the year. In the fourth quarter, FDA gave the green light to Tecentriq in combination with Avastin for a specific form of lung cancer. The regulator also granted accelerated approval for leukaemia drug Venclexta, and approved Xofluza, which is used to treat the flu.
At the end of the year it was announced that Roche's CEO, Daniel O'Day, was stepping down from the helm after being with the company for more than 30 years in various roles. William Anderson succeeded him as the new chief executive at the start of 2019, having previously served as CEO of Genentech since 2017.
In 2018, Roche concluded several oncology-focused transactions to advance its personalized healthcare strategy with three U.S.-based acquisitions.
Three years after buying a majority stake in Foundation Medicine for more than $1 billion as part of a research and development collaboration, Roche acquired the rest of the company in a $2.4 billion follow-on deal for the business, which selects cancer treatments for patients based on their genetic profile.
The deal came on the heels of Roche's $1.9 billion acquisition of oncology-focused electronic health record (EHR) software developer Flatiron Health. They make oncology-specific EHR systems, most notably an information exchange platform which allows researchers to access and learn from patient records. The company's message is that large amounts of data could be used to speed up and, in some cases, replace certain clinical trials where patients are randomly assigned to a specific treatment.
Roche also entered an agreement to acquire Ignyta, a U.S. based pharmaceutical company focused on developing cancer therapies, for $1.7 billion. The acquisition expands Roche's oncology portfolio globally. Ignyta will continue its operations in San Diego and will be responsible for the ongoing study of entrectinib, its most advanced cancer drug being studied in a range of solid tumor types. The company also has a portfolio of drugs in early stage of development that use gene therapy to kill the underlying diseases that drive cancer tumor growth. Ignyta employs an integrated "Rx/Dx" approach that combines precision medicines (Rx) and in-house molecular diagnostics (Dx) to both identify and target hard-to-treat cancers in hard-to-find patients.
Roche entered several cancer research collaborations during the year. In the cellular therapy arena, it formed a deal with SQZ Biotechnologies to jointly develop and commercialize certain products based on antigen presenting cells (APCs) created by the SQZ platform for the treatment of oncology indications. The companies are also expanding a 2015 collaboration to jointly develop therapeutics derived from peripheral blood mononuclear cells (PBMCs).
With Kymab Group, Roche entered a clinical trial agreement, under which it will provide its PD-L1 blocking antibody atezolizumab for use in combination in Kymab's upcoming Phase I-II clinical studies combining its lead investigational anti-ICOS antibody therapy KY1044 in patients with advanced solid cancers. Kymab will be responsible for conducting the clinical trials, and both companies will share data from the trials. Kymab continues to retain all commercial rights to KYI044.
Syapse and Roche entered into a multi-year strategic collaboration to help make precision medicine available to more cancer patients. Syapse and Roche will work jointly to develop software products and analytics solutions to provide the tools and insights healthcare providers need to practice precision medicine at scale, with the goal of improving patient outcomes. The companies will initially focus on four product programs: real-world evidence, so that physicians can make better care decisions; better understanding the health economics impact and patient outcomes of precision medicine; advancing electronic patient-reported outcomes to understand precision medicine's effect on health-related quality of life; and accelerating clinical trial enrollment by matching patients to precision trials at the point of care.
Roche entered research deals in therapeutic areas other than cancer as well during the year. In diabetes, it partnered with Zealand Pharma for the Phase 3 trials with dasiglucagon for treatment of congenital hyperinsulinism (CHI). Zealand is responsible for conducting the Phase 3 trials, while Roche Diabetes Care provides its Accu-Chek Combo pump system for this study.
Icagen entered into a license and collaboration agreement with Roche to develop and commercialize small molecule ion channel modulators for the treatment of neurological disorders. The program incorporates Icagen's platform for ion channels and is directed at a specific novel ion channel target expressed in neurons.
With BioMed X, Roche entered a research collaboration in the field of immunology. BioMed X launched a global call for applications to establish a new biomedical research group in Heidelberg, Germany with the goal of developing novel approaches for the treatment of several immune-mediated diseases.
Caption: Roche bolstered its oncology portfolio during the year, striking deals to buy Foundation Medicine, Flatirion Health and Ignyta. (Courtesy of Roche)
04 JOHNSON & JOHNSON
Headquarters: New Brunswick, NJ
HEADCOUNT: 135,100 REVENUES: $81,581 (+7%) PHARMA REVENUES: $40,734 (+12%) NET INCOME: $15,297 (N/M) R&D: $10,775 (+2%)
DRUGS APPROVED DRUG INDICATION Erleada HIV treatment Motegrity Prostate cancer Symtuza Constipation DRUGS FILED DRUG INDICATION Cabotegravir & Rilpivirine HIV treatment PHASE III DRUG INDICATION Ponesimod Relapsing-Remitting MS (RRMS) Aprocitentan Hypertension (HTN) Dapivirine HIV prophylaxis Redectane Nuclear imaging Seladelpar Primary biliary cirrhosis (PBC) Rilpivirine LAI HIV treatment MOR202 Multiple myeloma Pimodivir Influenza MVA-BN Filo Ebola haemorrhagic fever (EHF) prophylaxis Monovalent Ebola Vaccine Ebola haemorrhagic fever (EHF) prophylaxis Daratumumab Enhanze Multiple myeloma, Amyloidosis Zejula Prostate cancer TOP1630 Dry eye Ad26.Mos4.HIV HIV prophylaxis Abiraterone- Apalutamide FDC Prostate cancer Paliperidone 6-month Injectable Schizophrenia Uptravi IV Pulmonary hypertension TD-1473 Ulcerative colitis EARLY RESEARCH PROJECTS DRUG INDICATION Ipilimumab prostate cancer Pimodivir Kidney Failure, Chronic JNJ-64300535 Hepatitis B, Chronic JNJ-63723283 Neoplasm JNJ-67571244 Leukemia, Myeloid, Acute JNJ-67856633 Leukemia, Lymphocytic, Chronic, B-Cell JNJ-64619178 Neoplasms, Non-Hodgkin Lymphoma, Myelodysplastic Syndromes JNJ-64407564 Hematological Malignancies JNJ-63733657 Alzheimer Disease JNJ-63709178 Leukemia, Myeloid, Acute JNJ-61186372 Non-Small-Cell Lung Cancer JNJ-68284528 Multiple Myeloma
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Invega Sustenna Schizophrenia 2019 Prezista HIV 2019 Simponi Arthritis, rheumatoid 2022 Stelara Psoriasis 2023
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Stelara psoriasis $5,156 29% Remicade rheumatoid arthritis $4,890 -15% Zytiga prostate cancer $3,498 40% Xarelto deep vein thrombosis, pulmonary embolism $2,477 -1% Invega Sustenna schizophrenia $2,429 10% Simponi rheumatoid arthritis $2,084 14% Darzalex Multiple myeloma $2,025 63% Prezista HIV/AIDS $1,955 7% Imbruvica oncology $1,486 41% Opsumit hypertension $1,215 112%
Johnson & Johnson's (J&J) pharmaceutical segment sales in 2018 were $40.7 billion, an increase of 12% from 2017. U.S. sales accounted for $23.3 billion while international sales were $17.4 billion, an increase of 8.4% and 18% respectively. The pharma segment is focused on six therapeutic areas: immunology, infectious diseases and vaccines, neuroscience, oncology, cardiovascular and metabolism and pulmonary hypertension, a new therapeutic area, which was established with the $30 billion acquisition of Actelion in June 2017.
During the year, FDA approved J&J's cardiovascular drug Invokana (canagliflozin). The drug is meant to reduce the risk of major adverse cardiovascular events, including heart attack, stroke or death due to a cardiovascular cause in adults with type 2 diabetes who have established cardiovascular disease. It is the first and only oral diabetes treatment approved with this indication. FDA also signed off on a Janssen Phase lb/2 trial to evaluate a chimeric antigen receptorT cell (CAR-T) therapy in patients with relapsed or refractory multiple myeloma
In terms of acquisitions, while 2018 didn't witness anything on the level of the Actelion deal a year earlier, J&J did buy BeneVir Biopharm for as much as $1 billion. BeneVir uses itsT-Stealth Oncolytic Virus Platform to engineer oncolytic viruses tailored to infect and destroy cancer cells. Janssen intends to advance preclinical candidates as standalone therapies and in combination with other immunotherapies for the treatment of solid tumor cancers. BeneVir will maintain a research presence in Rockville, MD and become part of the Janssen Oncology Therapeutic Area.
RESEARCH AND DEVELOPMENT PARTNERSHIPS
During the year J&J entered a number of partnerships to advance its research and development activities. Biopharma Ireland Limited joined a global co-development and commercialization agreement with Janssen Biotech, one of the Janssen Pharmaceutical Companies of J&J, for TD-1473 and related back-up compounds for inflammatory intestinal diseases, including ulcerative colitis and Crohn's disease. The deal could be worth up to $1 billion and will see the two companies jointly develop and commercialize TD-1473 in inflammatory intestinal diseases, with the two companies sharing profits in the U.S. and expenses related to a potential Phase 3 program.
Arrowhead Pharmaceuticals entered into a license and collaboration agreement with Janssen to develop and commercialize ARO-HBV. In addition, Arrowhead entered into a research collaboration and option agreement with Janssen to potentially collaborate for up to three additional RNA interference (RNAi) therapeutics against new targets to be selected by Janssen. The transactions have a combined potential value of over $3.7 billion for Arrowhead.
argenx, a clinical stage biotech, entered a $1.6 billion global collaboration and license agreement for cusatuzumab (ARGX-110), an anti-CD70 SIMPLE AntibodyO, with Cilag GmbH, an affiliate of Janssen. Cusatuzumab is currently in development in a Phase 1/2 combination study with Vidaza for newly diagnosed, elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) who are unfit for chemotherapy.
MeiraGTx entered into a research collaboration and evaluation agreement with Janssen to use their proprietary riboswitch technology to engineer regulatable gene therapy constructs encoding proprietary gene sequences from Janssen. Evaluation of the performance of these constructs will determine the utility of this approach in future product development. MeiraGTx's gene regulation platform is a potentially transformative technology that incorporates an on/off switch for gene expression into the gene therapy vector which can then be activated using a small molecule. In this way, gene therapies can be switched on and off according to the patients' need and the dosing requirements of the therapy. Temporal control overlaying spatial regulation of gene expression has the potential to increase the utility and flexibility of gene therapy.
Together with Theravance Biopharma, J&J will develop TD1473, a first-in-class oral, gastrointestinal (GI) restricted pan-Janus kinase OAK) inhibitor for the treatment of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC).
NEW ASIA PACIFIC HO
Expanding its global footprint, and reflecting positive growth overseas, in May 2018 J&J opened its new Asia Pacific headquarters in Singapore. The new 15,800 square meter facility will bring together more than 1,000 employees from Johnson & Johnson's pharmaceuticals, medical devices and consumer businesses in one single location to spearhead new ideas and frameworks for healthcare of the future. The headquarters will feature a Design Lab, Leadership Lab, and Human Performance Institute. Johnson & Johnson's Asia Design Lab will be the first design lab outside of the U.S.
The new Singapore HQ has also been selected as the location for Johnson & Johnson's first global development center known as the Leadership Lab. The Leadership Lab aims to conduct over 200 leadership development classes and train 4,000 Asian leaders annually. As a think-tank, the Leadership Lab will create links with universities, research groups, governments, healthcare organizations and other partners to co-create new healthcare models and solutions to prototype capabilities required to author the next chapter of healthcare innovation in Asia.
The regional headquarters will also include Asia Pacific's first Human Performance Institute (HPI), offering proprietary leadership development initiatives to participants outside of Johnson & Johnson, with the goal to train 150,000 people in Singapore by 2020.
Caption: J&J maintained its spot at number four in this year's ranking on $40.7 billion in 2018 revenue.
Headquarters: Paris, France
HEADCOUNT: 104,226 YEAR ESTABLISHED: 2004 REVENUES: $39,419 (-2%) NET INCOME: $4,925 (+1%) R&D: $6,742 (+8%)
DRUGS APPROVED DRUG INDICATION Libtayo Skin cancer, non-melanoma Vaxelis Diphtheria prophylaxis, Hepatitis B pro phylaxis, Haemophilus influenzae type b (Hib) prophylaxis, Pertussis/Whooping cough, Polio prophylaxis, Tetanus DRUGS FILED DRUG INDICATION Isatuximab Multiple myeloma PHASE III DRUG INDICATION Fitusiran Haemophilia A, B Sutimlimab Anaemia, haemolytic Efpeglenatide Diabetes, type II (maturity onset) GZ402666 Pompe's disease GZ402671 Polycystic kidney disease (PKD) MEDI8897 RSV infections Fasinumab Osteoarthritis, chronic pain Rabies VRVg Rabies TetraMen-T Meningitis prophylaxis Picoplatin Small cell lung cancer (SCLC) Evinacumab Familial hypercholesterolaemia Mavorixafor General haematological indications VN-0105 Haemophilus influenzae type b (Hib) pro phylaxis, Diphtheria prophylaxis, Pertussis/Whooping cough, Polio prophylaxis, Teta nus prophylaxis Vutrisiran Amyloidosis Ozoralizumab Arthritis, rheumatoid EARLY RESEARCH PROJECTS DRUG INDICATION SAR2720 solid tumors SAR440234 leukemia SAR441000 solid tumors BIW001 hemophilia A ST400 beta thalassemia BIW003 sickle cell disease SAR443060 amyotrophic lateral sclerosis Next Gen PCV pneumococcal conjugate vaccines Virus Type 2 Vaccine HSV-2 therapeutic vaccine Respiratory Syncytial Virus Vaccine vaccines for infants 4-months and older SAR441169 psoriasis SAR439459+ cemiplimab advanced solid tumors cemiplimab(l) + REGN4018 ovarian cancer SAR439859+ palbociclib metastatic breast cancer sutimlimab immune thrombocytopenic purpura SAR443060 Alzheimer's disease SAR441169 psoriasis SAR441344 multiple sclerosis SAR408701 mAb solid tumors SAR439459 advanced solid tumors REGN5458 relapsing refractory multiple myeloma REGN4018 ovarian cancer
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Jevtana Prostate cancer 2021 Aubagio Relapsing-Remitting MS (RRMS) 2023 Myozyme Pompe's disease 2023 Apidra Diabetes, type I (juvenile onset) 2023
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Lantus diabetes $4,211 -19% Pentacel vaccines $2,066 0% Influenza Vaccines vaccines $2,017 12% Aubagio Relapsing-Remitting MS (RRMS) $1,945 10% Lovenox thrombosis $1,730 -3% Plavix heart attack, stroke $1,701 2% Myozyme / Lumizyme Pompe disease $992 11% Toujeo diabetes $992 8% Dupixent Eczema/Dermatitis $931 276% Fabrazyme Fabry disease $892 9%
Revenue fell slightly for Sanofi in 2018 as it continued to restructure its operations to focus on mature markets and across emerging markets. The French pharma major reported sales of $39.4 billion, down 2% from the year prior, and slid two spots to number five in this year's ranking.
During the year, Sanofi changed the organizational structure of two of its global business units, creating a new primary care unit that combines the product portfolios of the existing diabetes and cardiovascular unit with established products. The new primary care unit will focus exclusively on mature markets.
Sanofi also created a second new global business unit called China and emerging markets. This newly-formed business will focus on the growth opportunities in emerging markets, particularly in China, which is Sanofi's second largest market after the U.S.
In-line with these plans to focus efforts on emerging markets, particularly China, Sanofi launched global R&D operations in the country during the year. The new Global R&D Operations Hub is focused on digitalization and big data analysis and located in Chengdu, Sichuan province, China. The new R&D operations in China will serve as Sanofi's third pillar of Sanofi Global Clinical Sciences and Operations, joining facilities in France and the U.S.
The 66 million [euro] investment will support the clinical research and development of Sanofi's drugs by focusing on the management of global multi-center clinical trials data and files. The hub will bring together global data and analysis in an effort to accelerate the availability of trial results, from Phase I to Phase IV.
The Chengdu Hub will target therapeutic areas including diabetes and cardiovascular diseases, vaccines, oncology, immunology and inflammation, rare diseases, multiple sclerosis and neurology. It will leverage global cutting-edge biological technology for polypeptides, gene therapy, monoclonal antibodies and multi-specific antibodies. The Hub plans to recruit 300 local pharmaceutical R&D professionals by 2020.
In another major investment, Sanofi is pouring nearly $400 million into the construction of a new state-of-the-art vaccine manufacturing facility at the Sanofi Pasteur Canadian headquarters in Toronto, Ontario, Canada. The new facility will allow Sanofi Pasteur, the vaccines global business unit of Sanofi, to meet the growing demand of five-component acellular pertussis (5-acP) antigen. Upon completion in 2021, the new building will also be equipped to produce the antigens used in the diphtheria and tetanus vaccines.
M&A DEALS AND DIVESTMENTS
Sanofi signed a few acquisition and divestment agreements during the year as part of its refocused strategy. The largest deal in terms of dollars was the $11.6 billion acquisition of Bioverativ, a biopharma company focused on therapies for hemophilia and other rare blood disorders. Bioverativ was created from Biogen's hemophilia-focused spinoff launched in early 2017.
Hemophilia represents the largest market for rare diseases, with approximately 181,000 people affected worldwide, and is expected to grow above 7% per year through 2022. Bioverativ has approximately $10 billion in annual sales. It's extended half-life therapies, Eloctate and Alprolix for the treatment of hemophilia A and B, respectively, represented the first major advancements in the hemophilia market in nearly two decades when launched.
In 2016, Bioverativ generated $847 million in sales and $41 million in royalties.
Sanofi believes factor replacement therapy will remain the standard of care in hemophilia for many years due to its safety and increasingly superior long-acting profile. Sanofi will be able to leverage Bioverativ's clinical expertise and commercial platform to advance fitusiran, an investigational RNA interference (RNAi) therapeutic for hemophilia A and B, with or without inhibitors.
Bioverativ's pipeline includes a Phase III program for cold agglutinin disease, and early stage research programs and collaborations in hemophilia, and other rare blood disorders, including sickle cell disease and beta thalassemia.
In another acquisition, Sanofi purchased Ablynx, a biopharma company focused on the discovery and development of nanobodies, for approximately $4.8 billion. Sanofi said the acquisition is part of its innovation efforts focused on technologies addressing multiple disease targets with single multi-specific molecules.
Nanobodies are a new class of next-gen biologics. Ablynx's nanobody technology supports an extensive pipeline of more than 45 proprietary and partnered candidates for a range of therapeutic areas such as hematology, inflammation, immuno-oncology and respiratory diseases. Eight nanobodies have entered clinical development.
On the divestment front, Sanofi sold its European generics business to Advent International for roughly 1.9 billion [euro], as part of a continued effort to focus on its core areas of global medicines and emerging markets, specialty care and diabetes and cardiovascular. Sanofi's chief executive officer at the time, Olivier Brandicourt*, had planned to sell the business back in 2015 as part of the refocusing effort. Since then, Sanofi also sold its animal health business Merial, purchased Boehringer Ingelheim's consumer health assets, and made the aforementioned acquisitions of Ablynx and Bioverativ.
Sanofi also sold off its UK contract manufacturing organization (CMO) business. Recipharm bought the manufacturing center and business in Holmes Chapel, UK. The site manufactures flutiform for Vectura Group. As part of the transaction, Sanofi entered into a long-term supply agreement for the products currently manufactured at the facility, including metered dose inhalers and nasal sprays.
* Note: As this issue goes to press, Paul Hudson will begetting ready to take over the chief executive role upon Mr. Brandicourt's retirement.
Caption: Sanofi Pasteur, the vaccines division of the multinational pharmaceutical company, is investing 350 million [euro] in a new manufacturing facility.
Headquarters: Whitehouse Station, NJ
HEADCOUNT: 69,000 REVENUES: $42,294 (+5%) PHARMA REVENUES: $37,689 (+6%) NET INCOME: $6,220 (>100%) R&D: $9,752 (-6%)
DRUGS APPROVED DRUG INDICATION Delstrigo HIV treatment Pifeltro HIV treatment llumya Psoriasis Vaxelis Diphtheria prophylaxis, Hepatitis B pro phylaxis, Haemophilus influenzae type b (Hib) prophylaxis, Pertussis/Whooping cough, Polio prophylaxis, Tetanus DRUGS FILED DRUG INDICATION Relebactam Gram negative infections Ubrogepant Migraine Lusduna Diabetes, type I (juvenile onset), type II MK-7655A General bacterial indications PHASE III DRUG INDICATION V114 Pneumococcal infection prophylaxis Vericiguat Congestive heart failure (CHF) Gefapixant Cough/Common cold Ibrexafungerp Candidiasis, Aspergillosis infections Serlopitant Other dermatoses, Pruritus, Eczema/Dermatitis, Psoriasis Sarasar Hepatitis D treatment QMF149 Asthma Instiladrin Bladder cancer Atogepant Migraine Selumetinib Other neurological indications, solid tumors EARLY RESEARCH PROJECTS DRUG INDICATION MK-7684 Neoplasms MK-4280 Neoplasms M4344 advanced solid tumor MK-7264 Obstructive Sleep Apnea MK-2060 Kidney Failure, Chronic MK-8558 HIV-1 infection V114 Pneumococcal Infections V160 Cytomegalovirus Infections MK-5475 Pulmonary Arterial Hypertension MK-4334 Alzheimer's Disease M6495 Osteoarthritis, Knee
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Noxafil fungal infections 2019 RotaTeq Rotaviral gastroenteritis 2019 Bridion Anaesthesia, reversal 2021 Januvia diabetes 2022 Janumet diabetes 2022
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Keytruda cancer $7,171 88% Januvia diabetes, obesity $3,686 -1% Gardasil HPV vaccine $3,151 37% Janumet diabetes, obesity $2,228 3% Isentress HIV/AIDS $1,140 -5% Bridion Anaesthesia, reversal $917 30% Pneumovax vaccines $907 10% NuvaRing contraception $902 19% Simponi rheumatoid arthritis $893 9% Zetia/vytorin cholesterol $857 -36%
Merck's worldwide pharma sales were $37.7 billion in 2018, an increase of 6% compared with 2017. Growth was driven primarily by higher oncology drug sales, particularly from star pupil Keytruda--sales skyrocketed 88% from the year before to reach $7.2 billion. Revenue related to Lynparza and Lenvima also helped bottom line growth. Other revenue generators included higher sales of vaccines, driven primarily by human papillomavirus (HPV) vaccine Gardasil/Gardasil 9, as well as higher sales in the hospital acute care franchise, attributable to Bridion and Noxafil.
Growth in 2018 was hindered by declines in the virology franchise, including lower sales of hepatitis C virus treatment Zepatier, as well as lower sales of shingles vaccine Zostavax. Generic and biosimilar competition for cardiovascular drugs Zetia and Vytorin, and immunology product Remicade, also hurt growth.
During the year, Merck continued to build its oncology portfolio through acquisition and collaboration. In February it bought virus-based cancer drug firm Viralytics for $394 million. The deal gave Merck full rights to Cavatak, Viralytics' investigational on-colytic immunotherapy that is based on the company's proprietary formulation of an oncolytic virus that has been shown to preferentially infect and kill cancer cells. Cavatak is currently being evaluated in multiple Phase 1 and 2 trials, with Keytruda--the two companies formed a partnership back in 2015 to study the use of the Cavatak and Keytruda combination in melanoma, prostate, lung and bladder cancers.
With Dragonfly Therapeutics, Merck entered a deal to discover immunotherapies for solid tumor cancers, under which Merck has the option to license exclusive worldwide rights to products developed using Dragonfly's TriNKET technology platform for a number of solid-tumor programs.
Moderna Therapeutics and Merck expanded their 2016 collaboration to develop and commercialize personalized messenger RNA (mRNA) cancer vaccines to now include shared antigen mRNA cancer vaccines including mRNA-5671, Moderna's mRNA KRAS cancer vaccine. The two companies will now advance jointly mRNA-5671 in human studies, and plan to conduct combination studies with additional immuno-oncology therapies.
Evelo Biosciences entered into a clinical trial collaboration with Merck to evaluate EDP1503 in combination with Keytruda in multiple cancer indications; Rexahn Pharmaceuticals also entered into a clinical trial agreement to evaluate the combination of its RX-5902 and Keytruda in a Phase 2 breast cancer trial; Immutep and Merck are evaluating the combination of Immutep's lead immunotherapy product candidate eftilagimod alpha with Keytruda; and with Eisai, Merck partnered for the worldwide co-development and co-commercialization of cancer drug Lenvima--the companies will develop and commercialize Lenvima jointly, both as monotherapy and in combination with Keytruda.
REGULATORY MILESTONES AND CLINICAL PROGRESS
Keytruda continued to spread its wings during the year with multiple new indications across several tumor types, including approval from FDA for the treatment of cervical cancer, a type of non-Hodgkin lymphoma, hepatocellular carcinoma, Merkel cell carcinoma, and in combination with chemotherapy for the treatment of a type of lung cancer. It also received approvals from the European Commission, as well as Chinese and Japanese regulators.
Lynparza, which is being developed in a collaboration with AstraZeneca, received FDA approval for use in breast cancer and ovarian cancer. Additionally, Lenvima was approved in the U.S., EU, Japan and China for the treatment of hepatocellular carcinoma. The FDA and EC also approved two new HIV-1 medicines: Delstrigo, a once-daily fixed dose combination tablet of doravirine, lamivudine and tenofovir disoproxil fumarate; and Pifeltro (doravirine), a new non-nucleoside reverse transcriptase inhibitor to be administered in combination with other antiretroviral medicines.
In addition to the recent approvals, Merck has continued to advance its late-stage pipeline with several regulatory submissions. Keytruda is under review in the U.S. in combination with axitinib for renal cell carcinoma and has been granted Priority Review by the FDA.
The company's Phase 3 oncology programs includes Keytruda in the therapeutic areas of breast, cervical, colorectal, esophageal, gastric, hepatocellular, mesothelioma, nasopharyngeal, ovarian, renal and small-cell lung cancers; Lynparza for pancreatic and prostate cancer; and Lenvima in combination with Keytruda for endometrial cancer.
Additionally, the company has candidates in Phase 3 clinical development in several other therapeutic areas, including V114, a vaccine for pneumococcal disease that received Breakthrough Therapy designation; MK-7264, gefapixant, a selective, nonnarcotic, orally-administered P2X3-receptor agonist being developed for the treatment of refractory, chronic cough; and MK1242, vericiguat, an investigational treatment for heart failure.
On the drug discovery front, Merck and IRBM formed a new agreement in the peptide therapeutics area, continuing their long-standing history of collaboration that began in 2010.
According to the companies, there has been increasing interest in peptide research over the last 15 years. The pharma industry continues to make significant preclinical and clinical investments in peptide-based therapeutics for different areas, including metabolic diseases, oncology and cardiovascular disease. Over the last decade there have been numerous technological advancements in this field. Now characteristics that were previously considered a liability for peptides, such as screening systems for lead identification, half-life, stability, solubility, formulation and delivery routes, are no longer considered insurmountable obstacles.
IRBM has built broad expertise in peptide drug development, from initial target identification to the development of a clinical candidate with the required properties in terms of specificity, potency, pharmacokinetics, metabolism and toxicology. For this project, IRBM will be applying its expertise in phage display peptide library design and screening and in chemical peptide synthesis and optimization, to identify potential peptide leads for a specific Merck target.
Caption: Merck reported positive revenue growth in 2018 backed by strong sales of cancer drug Keytruda.
Headquarters: North Chicago, IL
HEADCOUNT: 30,000 YEAR ESTABLISHED: 2013 REVENUES: $32,753 (+16%) NET INCOME: $5,687 (+7%) R&D: $10,329 (+106%)
DRUGS APPROVED DRUG INDICATION Orilissa Endometriosis DRUGS FILED DRUG INDICATION Leronlimab HIV treatment Upadacitinib Arthritis, rheumatoid PHASE III DRUG INDICATION Veliparib Breast cancer, Non-small cell lung cancer (NSCLC), Ovarian cancer, Lung cancer Eltoprazine Attention deficit disorder/hyperactivity (ADD/ADHD) Abexinostat Renal cell carcinoma (RCC) Rova-T Small cell lung cancer (SCLC) ABBV 951 Parkinson's disease EARLY RESEARCH PROJECTS DRUG INDICATION ABBV-157 immune-mediated diseases ABBV-011 small-cell lung cancer ABBV-085 solid tumors ABBV-151 solid tumors ABBV-155 solid and hematologic tumors ABBV-167 solid and hematologic tumors ABBV-181 solid tumors ABBV-2029 solid and hematologic tumors ABBV-321 solid tumors ABBV-368 solid tumors ABBV-428 solid tumors ABBV-621 solid and hematologic tumors ABBV-647 solid tumors ABBV-744 acute myeloid leukemia and metastatic castration-resistant prostate cancer ABBV-927 solid tumors ABBV-0805 Parkinson's disease ABBV-951 Parkinson's disease Elezanumb (ABT-555) spinal cord injury ABBV-4083 filarial diseases CF Combo cystic fibrosis
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Humira rheumatoid arthritis 2023
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Humira rheumatoid arthritis 2023
AbbVie's revenues grew 16% to $32.8 billion in 2018 driven primarily by sales growth related to Mavyret, Imbruvica and Venclexta and the continued strength of Humira. The arthritis blockbuster again topped the 2018 list of top selling drugs, raking in $19.9 billion in sales--an increase of 8.2%. Bio-similar competition is expected to hurt Humira sales in 2019, but is not expected to be an issue in the U.S. until 2023.
Cancer drugs Imbruvica and Venclexta both reported positive growth. Imbruvica revenue was $3.6 billion, an increase of 39.5%, driven by market share growth in front-line chronic lymphocytic leukemia (CLL) and other approved indications. Venclexta increased its sales by more than 100% in 2018 primarily due to market share gains following FDA and EMA approvals in combination with Rituxan. Hep C drug Mavyret's sales increased by more than 100% in 2018 after its approval by FDA and EMA in the second half of 2017 as well as further geographic expansion in 2018. Mavyret's penetration into the market hurt revenues of fellow hep C drugViekira, whose sales decreased by 76% in 2018.
AbbVie's pipeline includes more than 60 compounds or indications in development across immunology, oncology and neuroscience, with additional targeted investments in cystic fibrosis and women's health.
AbbVie achieved a number of regulatory milestones for several key products in 2018, including regulatory approvals for cancer drugVenclexta in combination with Rituxan (rituximab) and in combination with azacitidine or decitabine; Imbruvica was also approved in combination with rituximab for cancer treatment. In addition, the company introduced Orilissa, the first FDA-approved oral treatment in over a decade for the management of moderate to severe pain associated with endometriosis.
With more than 30 programs in mid- and late-stage development, some highlights from AbbVie's pipeline advancements in 2018 including having completed registrational studies and submitted regulatory applications for the company's next-generation immunology assets, upadacitinib and risankizumab, in rheumatoid arthritis and psoriasis, respectively. In addition, the company initiated several Phase 3 programs for these assets including studies for upadacitinib in atopic dermatitis and ulcerative colitis, as well as risankizumab in Crohn's disease.
EXTENDS R&D ALLIANCE WITH CALICO
AbbVie and Calico extended their collaboration to discover, develop and market new therapies for patients with age-related diseases, including neurodegeneration and cancer.
Calico is the Alphabet-backed life sciences company that is led by former Genentech chairman and chief executive officer Arthur D. Levinson, Ph.D. Calico has a research and development facility in the San Francisco Bay Area and more than 150 employees.
The collaboration has been extended for an additional three years. Calico will be responsible for research and early development until 2022 and will advance collaboration projects through Phase Ha through 2027. AbbVie will continue to support Calico in its early R&D efforts and, following completion of Phase Ha studies, will have the option to manage late-stage development and commercial activities. Both parties will share costs and profits. AbbVie and Calico will each commit to contribute an additional $500 million to the collaboration.
Since 2014, the collaboration has produced more than two dozen early-stage programs addressing disease states across oncology and neuroscience and yielded new insights into the biology of aging.
In other R&D tie-ups, AbbVie and Calibr entered a collaboration to develop T-cell therapies aimed primarily at cancer, including solid tumors, leveraging advanced precision medicine technology. AbbVie gains exclusive access to Calibr's switchable CAR-T platform for up to four years. The companies will work together to develop T-cell therapies directed to solid tumor targets identified by AbbVie. AbbVie also has the option to develop additional cell therapies toward AbbVie-nominated targets and license existing Calibr cell therapy programs under development for hematological and solid cancers, including Calibr's lead program.
Calibr plans to enter this lead candidate into clinical studies for lymphoma in 2019. In addition, the agreement provides AbbVie with an option to acquire an exclusive license to Calibr's switchable CAR-T platform and programs within the first four years of the collaboration. The companies will share responsibility for preclinical development, and AbbVie is responsible for clinical development and commercialization. Calibr is eligible to receive success-based milestone payments and royalties.
Calibr's cell therapy program is designed to enhance safety, versatility and efficacy through a proprietary modular "switchable" CAR-T cell that uses antibody-based switch molecules to control the activation and antigen specificity of CAR-T cells. Calibr's technology may enable the development of universal CAR-T-based treatments across several types of hematological and solid tumor indications.
With Voyager Therapeutics, AbbVie entered an exclusive strategic collaboration and option agreement to develop and commercialize vectorized antibodies directed against tau for the treatment of Alzheimer's disease and other neurodegenerative diseases. The collaboration combines AbbVie's monoclonal antibody expertise, global clinical development and commercial capabilities with Voyager's gene therapy platform that enables generating adeno-associated viral (AAV) vectors for the treatment of neurodegenerative diseases.
In healthy individuals, tau is an abundant protein in the brain that promotes cellular stability and function. In the diseased brain, altered tau accumulates, resulting in impaired brain function and neuronal cell loss. One of the limitations with current biologic therapies for neurodegenerative diseases is that only a small amount of drug makes it into the brain. This collaboration aims to develop a potential one-time treatment using Voyager's gene therapy platform to reduce tau pathology through the delivery of an AAV vector antibody that encodes the genetic instructions to produce anti-tau antibodies within the brain.
Lastly, AbbVie took over full development and commercial responsibility for its collaboration with Galapagos to discover and develop new therapies to treat cystic fibrosis (CF).The investigational program comprises several clinical and preclinical compounds originally discovered and developed jointly by AbbVie and Galapagos. Galapagos will not pursue further research and development in CF, but is eligible for future milestones and royalties on commercialized programs. Galapagos retains the right to future development of GLPG-2737 in non-CF indications. AbbVie is eligible to receive undisclosed future milestones and royalties in non-CF indications.
Caption: Arthritis blockbuster Humira was again the top selling drug of 2018 with nearly $20 billion in sales.(Courtesy of Abbvie)
Headquarters: Brentford, Middlesex, UK
HEADCOUNT: 95,490 YEAR ESTABLISHED: 2000 REVENUES: $40,992 (+1%) PHARMA REVENUES: $30,807 (+2%) NET INCOME: $5,381 (-2%) R&D: $5,178 (-14%)
DRUGS APPROVED DRUG INDICATION Krintafel Malaria DRUGS FILED DRUG INDICATION Travivo Depression Cabotegravir & Rilpivirine HIV treatment PHASE III DRUG INDICATION GSK2857916 Multiple myeloma Daprodustat Anaemia in chronic kidney disease (CKD) (dialysis), Anaemia in chronic kidney disease (CKD) (non-dialysis) Fostemsavir Tromethamine HIV treatment Dostarlimab Ovarian cancer GSK3196165 Arthritis, rheumatoid Camvia CMV infections Vynpenta Vasculitis Staxyn Erectile dysfunction S/GSK1265744 LAP HIV treatment, Pre-exposure prophylaxis (PrEP) Entinostat Breast cancer Arzerra S.C. Relapsing-Remitting MS cAd3-EBO Z Ebola haemorrhagic fever (EHF) prophylaxis EARLY RESEARCH PROJECTS DRUG INDICATION 1795091 cancer 3368715 cancer 35371420 cancer 2636771 cancer 3145095 pancreatic cancer TSR-033 cancer 3036656 tuberculosis 3810109 HIV infection 2831781 ulcerative colitis 3358699 rheumatoid arthritis 2983559 inflammatory bowel disease 3858279 pain in osteoarthritis nemiralisib activated PI3K delta syndrome 3511294 asthma 2292767 respiratory diseases 3439171 muscle repair
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Priorix MMR prophylaxis 2019 Veramyst Rhinitis, seasonal allergy 2021 FluLaval Influenza prophylaxis 2022 Rotarix Rotaviral gastroenteritis 2022 Benlysta Systemic lupus erythematosus 2023
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Triumeq HIV $3,535 11% Seretide/Advair asthma, COPD $3,234 -20% Tivicay HIV $2,188 21% Breo Ellipta COPD $1,454 12% Hepatitis franchise Hepatitis A, B $1,079 21% Shingrix Shingles prophylaxis $1,047 n/a Ventolin asthma $984 0% Pediarix pediatric vaccine $908 -5% Lamictal anti-epileptic $824 -2% Flovent respiratory $794 3%
GlaxoSmithKline (GSK) reported revenue of $40.9 billion, up just 1% from the year before. The standout was Shingrix, GSK's vaccine for shingles, which had sales of $1.0 billion in its launch year. HIV medicines also continued to grow with $3.5 billion in sales for Triumeq, GSK's new top seller, and $2.2 billion forTivicay.
With the decline if its flagship product Advair, GSK continues to build its new respiratory portfolio with Trelegy Ellipta, the new three-in-one medicine for chronic obstructive pulmonary disease (COPD), and Nucala, GSK's biologic medicine for severe asthma. In addition to the positive launches of Shingrix and Trelegy Ellipta, GSK reported a strong start to sales of HIV drug Juluca.
During the year GSK implemented a new R&D approach to focus on science of the immune system, human genetics and advanced technologies. In fact, it made significant progress in reshaping its pharmaceuticals R&D portfolio to reflect this new strategy with 33 of 46 new medicines now targeting modulation of the immune system.
As part of the its ongoing prioritization and strengthening of its pharmaceuticals pipeline, GSK transferred its portfolio of approved and investigational rare disease gene therapies to Orchard Therapeutics. GSK became an investor in Orchard as a result, receiving a 19.9% equity stake along with a seat on the company's board. GSK and Orchard will exchange manufacturing, technical and commercial insights and learnings on the development of gene therapy medicines to ensure the success of the assets.
In other business news, GSK entered a deal to create a consumer healthcare joint venture with Pfizer and bought out Novartis' stake in GSK Consumer Healthcare. The combination of the iconic brands of GSK and Pfizer will create one of the largest consumer healthcare players in key geographies including the U.S., Europe, China, India and Australasia. Pfizer will contribute its consumer healthcare business to GlaxoSmithKline's existing consumer healthcare business. The 2017 global sales for the combined business were approximately $12.7 billion. Pfizer receives a 32% equity stake in the joint venture.
The joint venture will be a category leader in pain relief, respiratory, vitamin and mineral supplements, digestive health, skin health and therapeutic oral health.
Following the integration, GSK said it intends to separate the joint venture as an independent company. GSK may also sell all or part of its stake in the joint venture in a contemporaneous IPO.
PUMPED UP PIPELINE
GSK strengthened its pipeline through business development initiatives with 23andMe and Tesaro. First, bolstering its cancer assets, GSK added the ovarian cancer drug Zejula to its portfolio when it paid $5.1 billion for Tesaro. The deal significantly strengthens GSK's pharmaceutical business, accelerating the build of its pipeline and commercial capability in oncology. Zejula (niraparib), a major marketed product, is an oral poly ADP ribose polymerase (PARP) inhibitor that is currently approved in the U.S. and Europe. Clinical trials to assess the use of Zejula in "all-comers" patient populations, as a monotherapy and in combinations, for the significantly larger opportunity of first line maintenance treatment of ovarian cancer are also underway.
With 23andMe, GSK entered a multi-year collaboration expected to identify novel drug targets, tackle new subsets of disease and enable rapid progression of clinical programs. The four-year collaboration will focus on research and development of innovative new medicines and potential cures, using human genetics as the basis for discovery. The collaboration will combine 23andMe's large-scale genetic resources and advanced data science skills, with the scientific and medical knowledge and commercialization expertise of GSK. The goal of the collaboration is to gather insights and discover novel drug targets driving disease progression and develop therapies for serious unmet medical needs based on those discoveries.
With over 5 million customers, 23andMe offers those with an interest in genetics the opportunity to learn more about their personal genetic profile. 23andMe customers can also choose to participate in research and contribute their information to a unique and dynamic database, which is now the world's largest genetic and phenotypic resource.
GSK brings extensive drug discovery and development capabilities across a broad range of diseases and modalities, including small molecule, biopharmaceuticals and cell and gene therapies. It will apply its technologies, including access to additional data sources, in-house target validation and genetics expertise, and utilize its manufacturing, commercial operations and scale to support partner activities across research and development.
GSK entered several research collaborations during the year, some of which are highlighted here. A research pact with Fimbrion Therapeutics led to the identification of an orally available, small molecule development candidate for the treatment and prevention of urinary tract infections. The discovery partnership began its joint research efforts in July 2016.
A three-year extension was made to a tie-up with Neomed-Labs. Under the terms of this renewed agreement, Neomed-Labs will develop immunotools (antigens), immunochemical assays as well as functional assays and undertake the clinical testing for several GSK vaccine projects at the clinical stage.
Neomed-Labs is a spin-out from GSK's Clinical Laboratory Services since April 2015 with a three-year original agreement. Following a successful transition from GSK, Neomed-Labs became a fully independent CRO in 2017 and is now collaborating with major global vaccine manufacturers.
With Syngene International, another global contract research services company, GSK formed a multiyear R&D agreement that will focus on accelerating the discovery of new drug candidates using Syngene's discovery services platforms. Syngene will setup a customized discovery research laboratory to support projects across several therapeutic areas. A team of Syngene scientists will work closely with GSK's global R&D teams on discovery research projects to identify new drug candidates with the potential to address some of the world's most pressing healthcare needs.
Lastly, GSK entered a technology agreement with LabCorp's Covance Drug Development business. GSK will use Covance's Xcellerate Monitoring, Xcellerate Insights, and Xcellerate Clinical Data Hub solutions in a software-as-a-service (SaaS) model. A key component of the technology licensed by GSK is Xcellerate Monitoring, Covance's implementation of risk-based monitoring, which enables assessment and mitigation of risk at the study, site and patient level. It also allows sponsors to strategically guide site monitoring resources and build quality and efficiency into their clinical trials, from commencement to completion.
Caption: The GlaxoSmithKline headquarters building in Brentford, West London. The British global pharmaceuticals company reported just a 1 % increase in revenue last year.
Headquarters: Indianapolis, IN
HEADCOUNT: 38,680 REVENUES: $24,556 (+7%) EARNINGS: $3,232 (NM) R&D: $5,307 (-1%)
DRUGS APPROVED DRUG INDICATION Olumiant Arthritis, rheumatoid Emgality Migraine, Cluster headaches Vitrakvi solid tumors DRUGS FILED DRUG INDICATION Lasmiditan Migraine Nasal Glucagon Hypoglycaemia Empagliflozin & Linagliptin & Metformin XR Diabetes, type II (maturity onset) Tadalafil Versafilm Erectile dysfunction PHASE III DRUG INDICATION LY3298176 Diabetes, type II (maturity onset) Mirikizumab Psoriasis, Ulcerative colitis, Crohn's disease Pegilodecakin Pancreatic cancer Flortaucipir F 18 Nuclear imaging Solanezumab Alzheimer's disease Tradipitant Eczema/Dermatitis Tanezumab Pain, lower back, Pain, cancer-induced, Osteoarthritis EARLY RESEARCH PROJECTS DRUG INDICATION Aur A Kinase Inhibitor cancer BTLA Agonist Antibody immunology Dual Amylin Calcitonin Receptor Agonist diabetes Mellitus ID01 Inhibitor cancer Oxyntomodulin diabetes Mellitus TIM-3 Monoclonal Antibody cancer BAFF/IL-17 Bispecific Antibody immunology Cancer oncology ERK Inhibitor cancer IL-23/CGRP Bispecific Antibody immunology PACAP38 Antibody pain Basal Insulin Acylated diabetes Mellitus CD200R Antibody Agonist immunology GDF15 Agonist diabetes IL-2 Conjugate immunology PD-1 Antibody Agonist immunology BTK Inhibitor cancer CXCR1/2 Ligands Monoclonal Antibody immunology GGG Tri-Agonist Diabetes diabetes O-GlcNAcase Inhibitor Alzheim's neurodegeneration PD-L1/TIM-3 Bispecific Antibody cancer
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Eraxis Candidiasis 2020 Livalo Hyperlipidaemia 2021 Alimta Mesothelioma 2022
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Trulicity diabetes $3,199 58% Humalog diabetes $2,997 5% Alimta cancer $2,133 3% Cialis erectile dysfunction $1,822 -21 % Forteo osteoporosis $1,576 -10% Humulin diabetes $1,331 0% Taltz Psoriasis $938 68% Cyramza stomach cancer $821 8% Basaglar diabetes $801 85% Cymbalta anxiety, depression $708 -6%
Ascending the ranks, Eli Lilly's products are performing well and key late stage assets are advancing. Despite generic competition for one of the company's best-selling products, Cialis, and slipping sales for flagship insulin products Humalog and Humulin, and other established brands, Forteo, Cymbalta, and Erbitux, revenues for the year were up 7%. Burgeoning sales of psoriasis and psoriatic arthritis drug Taltz, up 68% for the year, and diabetes products Trulicity, Basaglar, and Jardiance, up 58%, 85%, and 47%, respectively, helped to offset established product declines.
Also, newly launched breast cancer drugVerzenio is off to good start, and Emgality, approved in September for migraine prevention, and more recently for preventing episodic cluster headaches, offers tremendous potential with estimated peak annual sales of approximately $700 million. Lilly's numerous late stage assets include another promising migraine drug, lasmiditan, pending approval, and, in addition to expanded indications for top sellers, such Alimta, promising new candidates include mirikizumab, an immunology therapy being studied in Crohn's disease, and tanezumab being studied in osteoarthritic, back, and cancer pain.
Additionally, broadening its oncology portfolio, the pending $8 billion acquisition of Loxo Oncology will provide Lilly entry into precision medicine with approved and investigational medicines.
In addition to the pending acquisition of Loxo Oncology, Lilly has recently made several strategic moves, including the divestiture of its Animal health business, Elanco, which raised $1.5 billion in its stock market debut, and the sale of antibiotic assets in China for $375 million.
The Loxo Oncology acquisition was the largest in a series of strategic transactions to expand its oncology pipeline with externally sourced, first-in-class therapies. Loxo's pipeline of targeted medicines is focused on cancers that are uniquely dependent on single gene abnormalities that can be detected by genomic testing.
Among its assets, LOXO-292, an oral RET inhibitor that has been granted Breakthrough Therapy designation by the FDA for three indications, has an initial potential launch in 2020. RET fusions and mutations occur across multiple tumor types, including certain lung and thyroid cancers as well as a subset of other cancers.
Also, Vitrakvi, an oral TRK inhibitor developed and commercialized in collaboration with Bayer, was recently approved by the FDA. Vitrakvi is the first treatment that targets a specific genetic abnormality to receive a tumor-agnostic indication at the time of initial approval. LOXO-195, a follow-on TRK inhibitor is also being studied by Loxo and Bayer for acquired resistance to TRK inhibition, and has a potential launch in 2022.
This past March, Elanco Animal Health became a fully independent company. The spin-off is intended to provide a greater focus on Lilly's human pharmaceuticals business, which the company is heavily investing in.
Lilly recently sold the rights in China for two legacy antibiotics, Ceclor andVancocin, as well as a manufacturing facility in Suzhou, to Eddingpharm, a China-based specialty pharmaceutical company, in a transaction valued at $375 million.
Thanks to a recent head-to-head study, Talz is performing even better than expected. Talz surpassed Humira in reducing PsA disease activity by half and completely clearing patient skin after 24 weeks, according to data from a Phase IIIB/TV study. Thirty-six percent of the 234 trial patients treated with Taltz achieved both markers at 24 weeks, compared to 28% of Humira patients. Taltz also achieved its secondary endpoints of matching Humira in disease activity and surpassing it in clearing skin.
Representing a significant approval for Lilly, Emgality injection was approved by the FDA for the treatment of episodic cluster headache in adults. Emgality is an innovative therapeutic approach for this neurologic disease and the first and only calcitonin gene related peptide antibody approved by the FDA for two distinct headache disorders. Emgality was first approved by the FDA in September 2018 for the preventive treatment of migraine.
Also, Cyramza received approval from the FDA as a single agent for the treatment of patients with hepatocellular carcinoma (HCC), marking the fifth FDA approval for Cyramza. Importantly, the FDA has also removed the boxed warning from the labeling, which should boost sales further.
Additionally, the FDA approved a new indication for top seller Alimta in combination with Merck's Keytruda for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer, with no EGFR or ALK genomic tumor aberrations.
From its pain portfolio, Lilly and Pfizer achieved positive results from a Phase III study evaluating tanezumab in moderateto-severe chronic low back pain, meeting the primary endpoint demonstrating a statistically significant improvement in pain. Furthermore, Lilly has acquired several pain assets, gaining rights to CNTX-0290 from Centrexion Therapeutics for $47.5 million upfront and as much as $575 million in potential development milestones. CNTX-0290 is a small molecule somatostatin receptor type 4 (SSTR4) agonist currently in Phase I testing as a potential non-opioid treatment for chronic pain conditions.
Lilly also acquired all assets related to Hydra Biosciences' program of TRPA1 antagonists, currently being studied for the potential treatment of chronic pain syndromes.
Lilly has not given up on its diabetes therapeutic endeavors. Lilly bolstered its diabetes portfolio with Chugai's oral GLP-1 agonist, OWL833, a Phase I-ready asset being studied in type 2 diabetes. Also, Lilly and Boehringer recently submitted a NDA for the fixed-dose combination tablet of empagliflozin, linagliptin and metformin extended release for type 2 diabetes.
Lilly has several immunology alliances underway leveraging platform technologies of partner companies. A global alliance with Avidity aims to develop new medicines in immunology and other indications leveraging Avidity's technology platform to potentially overcome barriers to the delivery of oligonucleotides and target genetic drivers of disease.
A research collaboration leveraging Aduro's cGAS-STING Pathway Inhibitor program aims to develop immunotherapies for autoimmune and other inflammatory diseases. Additionally, an agreement with AC Immune will research tau aggregation inhibitor small molecules for the potential treatment of Alzheimer's disease and other neurodegenerative diseases leveraging AC Immune's Morphomer platform technology.
Caption: Lilly reported revenues of nearly $25 billion in 2018, a growth of 7%.
Headquarters: Thousand Oaks, OA
HEADCOUNT: 21,500 YEAR ESTABLISHED: 1980 REVENUES: $23,747 (+4%) NET INCOME: $8,394 (NM) R&D: $1,182 (+13%)
DRUGS APPROVED DRUG INDICATION Aimovig Migraine DRUGS FILED DRUG INDICATION ABP 710 Arthritis, rheumatoid, Ankylosing spondylitis, Crohn's disease, Ulcerative colitis, Psoriasis, Arthritis, psoriatic, General cancer indications PHASE III DRUG INDICATION Renexus General eye disorders Blisibimod IgA nephropathy Rilotumumab Non-small cell lung cancer (NSCLC) Ganitumab Bone cancer (Osteosarcoma) Tremelimumab Non-small cell lung cancer (NSCLC), Head & neck cancers, Bladder cancer, Hepa toma, liver cancer, Small cell lung cancer (SCLC) Tezepelumab Asthma Brazikumab Crohn's disease CNP520 Alzheimer's disease EARLY RESEARCH PROJECTS DRUG INDICATION AMG 119 small-cell lung cancer AMG 212 prostate cancer AMG 404 hematology/oncology AMG 427 acute myeloid leukemia AMG 570 systemic lupus erythematosus AMG 596 glioblastoma AMG 701 multiple myeloma AMG 966 inflammatory bowel diseases AMG 160 prostate cancer AMG 330 acute myeloid leukemia AMG 420 multiple myeloma AMG 510 solid tumors AMG 592 inflammatory diseases AMG 598 obesity AMG 757 small-cell lung cancer AMG 176 hematologic malignancies AMG 397 hematologic malignancies AMG 424 multiple myeloma AMG 562 non-Hodgkin's lymphoma AMG 594 heart failure AMG 673 acute myeloid leukemia AMG 890 cardiovascular disease IMYGIC mid-to-late-stage metastatic melanoma
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Vectibix Colorectal cancer 2020 Nexavar Renal cell carcinoma (RCC) 2020 Nplate Thrombocytopaenic purpura, idiopathic (ITP) 2022
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Enbrel rheumatoid arthritis $5,014 -8% Neulasta chemotherapy induced neutropenia $4,475 -1% Prolia bone cancer $2,291 16% Aranesp chemotherapy induced anemia $1,877 -9% Xgeva bone cancer $1,786 13% Sensipar/ Mimpara renal disease $1,774 3% Epogen anemia $1,010 -8% Kyprolis multiple myeloma $968 16% Nplate immune thromboytopenia $717 12% Vectibix colorectal cancer $691 8%
While Amgen's newer drugsProlia, Xgeva, Blincyto, Kyprolis continue to drive growth, its mature flagship products are facing rising competition. Sales of Neulasta and Neupogen are declining due to biosimilar competition from several companies, including Mylan and Coherus Biosciences. Several others face generic competition as well, including Enbrel, Aranesp and Epogen. Meanwhile, sales of Amgen's new migraine drug, Aimvoig, were unimpressive in the first quarter of 2019, and it's up against strong competition from Lilly's Emgality andTeva's Ajovy.
Amgen is successfully advancing its pipeline with the approval of osteoporosis drug Evenity in April, and Kanjinti, a biosimilar of Roche's breast cancer drug Herceptin, in June. This is the third biosimilar from Amgen's portfolio to receive approval, providing the potential for long-term revenues. Amgen expects to launch additional biosimilars in 2019.
As part of an effort to bolster its R&D efforts, Amgen recently offered to acquire Nuevolution, a drug discovery platform biotech company based in Denmark, for approximately $167 million. The Nuevolution board has recommended accepting the offer and Amgen expects to settle by July 15. The two companies have collaborated since October 2016 for drugs targeting multiple indications including two cancer programs. Having Nuevolution's discovery platform in-house may aid Amgen's discovery efforts for small molecules against difficult-to-drug targets and make the process more efficient.
Additionally, to further enhance its manufacturing capabilities, Amgen is expanding its campus in West Greenwich, RI with a new $160 million next-gen biomanufacturing plant that will be the first of its kind in the U.S. It will manufacture products for the U.S. and global markets. Amgen plans to incorporate multiple innovative technologies into a single facility, which is expected to be built in half the construction time with approximately half of the operating cost required of a traditional plant. Next generation biomanufacturing plants require a smaller manufacturing footprint offering environmental benefits such as reduced water and energy consumption, and lower levels of carbon emissions.
Among its more significant approvals, Amgen and UCB gained FDA approval for EVENITY for the treatment of osteoporosis in postmenopausal women at high risk for fracture. EVENITY is the first and only bone builder with a unique dual effect that both increases bone formation and to a lesser extent reduces bone resorption (or bone loss) to rapidly reduce the risk of fracture.
In October, the FDA approved the expanded indication for KYPROLIS to include a once-weekly dosing option in combination with dexamethasone for patients with relapsed or refractory multiple myeloma. The approval was based on Phase IE data demonstrating that KYPROLIS achieved superior progression-free survival and overall response rates, with a comparable safety profile, versus twice-weekly. The FDA reviewed the application under its Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.
Also, Amgen's BLINCYTO gained approval for relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in Japan, and an expanded indication as a monotherapy to include adult patients with Philadelphia chromosome negative (Ph-) CD19 positive B-cell precursor acute lymphoblastic leukemia (ALL) by the European Commission. Developed by a joint venture between Amgen and Astellas Pharma Inc., BLINCYTO is the first-and-only bispecific T cell engager (BiTE) immunotherapy construct approved globally. It's also the first approved immunotherapy from Amgen's BiTE platform, an approach that helps the body's immune system target cancer cells.
Amgen and its biosimilar partner Allergan, recently received approval from the FDA for Kanjinti, a biosimilar of Roche's breast cancer drug, Herceptin, for all approved indications of the reference product, HER2 adjuvant and metastatic breast cancer, and HER2 metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Since December of last year, the FDA approved four biosimilar versions of Herceptin including Kanjinti: Pfizer's Trazimera, Merck/Samsung Bioepis' Ontruzant, and Celltrion/ Teva's Herzuma).
Kanjinti is the third biosimilar from Amgen's portfolio to receive approval in the U.S. and Europe, joining Amjevita (a biosimilar of Abbvie's Humira) and Mvasi (a biosimilar of Roche's cancer drug Avastin). Currently, Amgen has 10 biosimilar products in its portfolio and a biosimilar version of Johnson & Johnson/Merck's Remicade (ABP 710) is under review in the U.S. and EU.
The collaboration with Allergan includes the development and commercialization of four oncology antibody biosimilars. A biosimilar version of Roche's Rituxan is in late-stage development for non-Hodgkin's lymphoma and rheumatoid arthritis.
Innovative oncology efforts are advancing as well. Amgen recently reported early data from a Phase I trial of AMG 510 showing promising activity in a study of 35 patients targeting one of the most commonly mutated genes in cancer. Analysts are suggesting it has the potential to be the next cancer blockbuster. Out of 10 lung cancer patients receiving Amgen's AMG 510 in the earlystage study, five went into partial remission and another four saw their disease stabilize. One patient experienced a complete remission four months after treatment. Representing a 90% disease control rate which is quite remarkable for a Phase I trial.
MG 510 targets KRAS G12c mutation, which accounts for about 13% of non-small cell lung cancers and 3% to 5% of colorectal cancers, and has been the subject of research for decades. While Amgen's results in colon cancer were less robust, ifs still too early to tell.
Furthermore, several interesting early research collaborations are underway. Most recently, a collaboration with Intermountain Health aims to rapidly develop new medicines. Amgen's subsidiary deCODE genetics will have access to the genomes of 500,000 participants from a study carried out by Intermountain Healthcare. Amgen hopes to use this data to uncover new insights into specific diseases and develop new medicines that reach the right disease targets. The collaboration aims to improve success rates and reduce drug development cycle times. To date, Amgen has accelerated the development timeline from early preclinical work through clinical development with several of its molecules, including AMG 510, currently in Phase I.
In October, Amgen made an equity investment of $66 million in Oxford Nanopore Technologies, a UK-based company advancing a new generation of portable genetic sequencing technology to perform direct, real-time sequencing of DNA and RNA. de-CODE Genetics uses Oxford's sequencing technologies to conduct genome research, including the identification and validation of new targets. The investment aligns with Amgen's strategic focus on using human genetics to develop new medicines.
Caption: Amgen's 4% growth to $23.7 billion in 2018 sales rounds out this year's top 10 companies.
11 BRISTOL-MYERS SQUIBB
Headquarters: New York, NY
HEADCOUNT: 23,300 YEAR ESTABLISHED: 1887 REVENUES: $22,561 (+9%) NET INCOME: $4,952 (NM) R&D: $6,345 (-2%)
DRUGS FILED DRUG INDICATION Travivo Depression Lumateperone Schizophrenia PHASE III DRUG INDICATION BMS-986165 Psoriasis Relatlimab Melanoma BMS-986205 Melanoma, Bladder cancer Sparsentan Focal segmental glomerulosclerosis (FSGS), IgA nephropathy Brivanib Hepatoma, liver cancer Pamrevlumab Pancreatic cancer, Pulmonary fibrosis, idiopathic Tremelimumab Non-small cell lung cancer (NSCLC), Head & neck cancers, Bladder cancer, Hepatoma, liver cancer, Small cell lung cancer (SCLC) Anifrolumab Systemic lupus erythematosus (SLE) Fostemsavir Tromethamine HIV treatment Rimegepant Migraine RG6206 Duchenne muscular dystrophy Bempegaldesleukin Melanoma, Renal cell carcinoma (RCC) BHV-3500 Migraine EARLY RESEARCH PROJECTS DRUG INDICATION APJ Agonist cardiovascular FPR-2 Agonist cardiovascular LPA1 Antagonist fibrotic diseases BTK Max immunoscience RORyT immunoscience S1P1 Agonsit immunoscience TLR 7/8 Antagonist immunoscience TYK2 Inhibitor immunoscience Anti-CD73 oncology Anti-CTLA-4 NF oncology Anti-CTLA-4 Probody oncology Anti-ICOS oncology Anti-TIGIT oncology Anti-TIM-3 oncology BET Inhibitor oncology CD80/-CD3 Oncolytic Virus oncology EP4 Antagonist oncology HuMax-IL8 oncology NLRP3 Agonist oncology STING Agonist oncology
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Orencia rheumatoid arthritis 2021 Atripla HIV 2021 Simponi rheumatoid arthritis 2022 Onglyza diabetes 2023 Stelara psoriasis 2023
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Opdivo melanoma, lung cancer, renal cancer $6,735 36% Eliquis deep vein thrombosis and pulmonary embolism $6,438 32% Sprycel leukemia $2,000 0% Orencia SC rheumatoid arthritis $1,381 11% Yervoy oncology $1,330 7% Orencia rheumatoid arthritis $1,329 8% Baraclude hepatitis B $744 -29% Reyataz HIV/AIDS $427 -39% Empliciti multiple myeloma $247 7% Nulojix kidney transplant $138 31%
Moving up in the ranks this year, Bristol-Myers Squibb is making headway in its efforts to become a premier specialty Biopharma company, overcoming losses associated with its Hep C franchise and culminating in the Opdivo era. For the past several years BMS held steady at 14, inching closer to the top 10 this year, and now with the pending $74 billion Celgene acquisition, potentially to the top five in 2020.
In 2018, double digit growth for prioritized brands Opdivo, which grew by $443 million, Eliquis, which grew by $342 million, Yervoy, which grew by $115 million, as well as Orencia, helped to offset significant declines in established brands Baraclude, Reyataz, Sustiva, and Hepatitis C franchises (for which revenues have all but disappeared), representing a total of $1.5 billion in lost revenue as compared to 2017.
Continued growth in the first quarter of 2019, with revenues up 14%, reaffirms the trajectory of the company's priority brands. Eliquis grew by $419 million, up 28%, Opdivo grew by $290 million, up 19%,Yervoy grew by $135 million, up 54%, and Orencia and Sprycel, were up 8% and 5%, respectively.
The Mega M&A news on January third, when BMS announced plans to acquire Celgene in a transaction valued at approximately $74 billion, will result in leading franchises in oncology (in both solid tumors and hematologic malignancies) led by Opdivo and Yervoy as well as Revlimid and Pomalyst; Immunology and Inflammation (led by Orencia and Otezla) and Cardiovascular Disease with Eliquis. The acquisition also expands Phase III assets with six expected near-term product launches representing more than $15 billion in revenue potential. Furthermore, Celgene's Revlimid, for the treatment of multiple myeloma, is one of the world's best-selling drugs. Sales were $9.7 billion in 2018, up 18%.
Following the acquisition, Thomas Lynch Jr., BMS'chief scientific officer will leave the company on October 1st. Rupert Vessey, a Celgene research executive will serve as president, Research & Early Development, overseeing drug discovery and the early clinical development. He will report to CEO Giovanni Caforio, and serve as a member of the leadership team. For late-stage assets, oncology expert Samit Hirawat, will service as chief medical officer, joining the company from Novartis.
Additional post-closing changes include, Nadim Ahmed from Celgene, who will manage the combined company's hematology business. The rest of the combined company's commercial side, including its cancer, immunology and cardiovascular businesses, will be managed by Chris Boerner, currently BMS'chief commercial officer. David Elkins, currently the chief financial officer of Celgene, will serve as executive vice president and chief financial officer.
The company continues to expand indications for its top seller Opdivo, and in April announced four-year survival results from pooled analyses of four studies in patients with previously-treated advanced non-small cell lung cancer who were treated with Opdivo.
In August of last year, the FDA approved Opdivo as the first and only immuno-oncology treatment option for patients with metastatic small cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy. Approval for this indication was granted under accelerated approval based on overall response rate and duration of response.
Small cell lung cancer is one of two main types of lung cancer and accounts for about 10% to 15% of all lung cancers. It's an aggressive disease that often goes undetected until the cancer is advanced.
Additional indications for Opdivo now include melanoma and kidney cancer. In July, it was approved by the European Commission (EC) for the adjuvant treatment of melanoma with involvement of lymph nodes or metastatic disease for both BRAF mutant and wild-type melanoma patients. With this decision, Opdivo became the first PD-1 therapy to receive a EC approval in the adjuvant setting, gaining its eighth indication across six distinct tumor types. Also, in January, the EC approved the combination of Opdivo plus Yervoy for the first-line treatment of patients with intermediate- and poor-risk advanced renal cell carcinoma.
BMS is also evaluating the Opdivo/Yervoy combo in late stage trials in castration-resistant prostate cancer and advanced or metastatic renal cell carcinoma. Also, in partnership with Infinity Pharmaceuticals, a Phase II trial is evaluating Opdivo in combination with Infinity's IPI-549 in patients with advanced urothelial cancer.
Despite its many successes, several indications for Opdivo fell short. BMS withdrew its supplemental Biologics License Application for the Opdivo and low-dose Yervoy combo for the treatment of first-line advanced non-small cell lung cancer (NSCLC) in patients with tumor mutational burden. After discussions with the FDA, further evidence on the relationship between TMB and PD-L1 is required to fully evaluate the impact of Opdivo plus Yervoy in this indication.
Also, in May, a Phase III trial evaluating Opdivo plus radiation versus temozolomide plus radiation in patients with newly diagnosed 06-methylguanine-DNA methyltransferase (MGMT)-unmethylated glioblastoma multiforme (GBM), did not meet its primary endpoint of overall survival (OS) at final analysis. Likewise, a Phase II trial evaluating Opdivo versus Opdivo plus Yervoy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck, did not meet its primary endpoints.
Sprycel, the company's next highest-selling oncology drug, gained an additional hematology indication. In January, the FDA expanded the indication for Sprycel tablets to include the treatment of pediatric patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in combination with chemotherapy, and shortly thereafter received the same approval by the EC.
EARLY RESEARCH EFFORTS
BMS and Tsinghua University are collaborating to discover therapeutic agents against novel targets for autoimmune diseases and cancers. The collaboration brings together their respective scientific expertise and capabilities with a focus on validating new targets and generating early drug candidates for clinical development. Ts-inghua University will conduct research on projects and BMS will have an option to exclusively license therapeutic resulting agents.
The collaboration expands an existing relationship that began in 2012 focused on autoimmune target discovery, structural biology research, as well as the science of mapping the 3D protein structure of biological molecular targets.
Lastly, a clinical collaboration with Compugen is evaluating Compugen's COM701, an investigational anti-PVRIG antibody, in combination with Opdivo in patients with advanced solid tumors, including non-small cell lung, ovarian, breast and endometrial cancer. In conjunction with this collaboration, BMS will make a $12 million equity investment in Compugen. Should Opdivo prove successful in treating ovarian and breast cancer, the sky is the limit for this breakthrough therapy.
Caption: The deal to acquire Celgene for $74 billion could see BMS move into the top five pharma companies in the coming years.
12 GILEAD SCIENCES
Headquarters: Foster City, CA
HEADCOUNT: 11,000 YEAR ESTABLISHED: 1987 REVENUES: $22,127 (-15%) NET INCOME: $5,455 (+18%) R&D: $5,018 (+34%)
DRUGS APPROVED DRUG INDICATION Biktarvy HIV Symtuza HIV PHASE III DRUG INDICATION Filgotinib Arthritis, rheumatoid, Crohn's disease Ulcerative colitis Selonsertib Nonalcoholic steatohepatitis (NASH) Brincidofovir Smallpox treatment Momelotinib Myelofibrosis Andecaliximab Stomach cancer Cilofexor Sclerosing cholangitis EARLY RESEARCH PROJECTS DRUG INDICATION GS-6207 HIV/AIDS Vesatolimod HIV/AIDS GS-9722 HIV/AIDS GS-4224 hepatitis B virus Axicabtagene ciloeucel diffuse large B-cell lymphoma KTE-X19 chronic lymphocytic leukemia KITE-718 solid tumor KITE-439 solid tumor GS-4875 inflammatory bowel disease
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Truvada HIV 2019 Epclusa Hepatitis C 2019 Harvoni Hepatitis C 2019 Atripla HIV 2021
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Genvoya HIV treatment $4,624 26% Truvada HIV treatment $2,997 -4% Epclusa Pre-exposure prophylaxis (PrEP) $1,966 -44% Odefsey Hepatitis C treatment $1,598 44% Descovy Liver cirrhosis $1,581 30% Harvoni HIV treatment $1,222 -72% Atripla HIV treatment $1,206 -33% Biktarvy Hepatitis C treatment $1,184 n/a Letairis HIV treatment $943 6% Ranexa HIV treatment $758 6%
Climbing out of a two-year downturn, the light at the end of the tunnel revealed itself in the first quarter of 2019, with revenues up 4% to $5.3 billion and earnings up 28% to $2.0 billion. Still recovering financially from HCV franchise declines, Gilead has finally returned to growth thanks to its flagship FUV franchise andYescarta, its first commercially available CAR-T cancer therapy.
While chronic hepatitis C virus (HCV) product sales, which consist of Epclusa, Harvoni,Vosevi, and Sovaldi, were down nearly 60% to $3.7 billion in 2018, and down 26% in the first quarter of 2019 to $790 million, HIV product sales were up 12% to $14.6 billion for the year, primarily due to the launch of Biktarvy and the continued uptake of Descovy, Genvoya and Odefsey. In 1Q19, HIV product sales were up 13% to $3.6 billion, thanks to Biktarvy.
Yescarta, a chimeric antigen receptor (CAR) T cell therapy launched in the U.S. in October 2017 to treat large B-cell lymphoma, generated $264 million in sales in 2018. Resulting from the 2017 acquisition of Kite Pharma, Yescarta was the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL).Yescarta generated $96 million in sales in the first quarter compared to $40 million in 1Q18.
Kite Pharma, a Gilead company, is significantly expanding its ability to manufacture a variety of CAR-T therapies, including Yescarta, for both clinical and commercial use with a new biologics facility in Urbana, MD. Kite specializes in cancer treatments and the facility will focus on chimeric antigen receptor T (CAR-T) therapies, which uses a patient's white blood cells to destroy cancer cells. Producing these therapies requires complex processes and the new facility aims to better meet these specifications. It will become part of Kite's commercial manufacturing network that includes sites in CA and the Netherlands. Yescarta is also being investigated in solid tumors. To date, CAR-T therapies have only proven successful in blood cancers.
As of March 1, 2019, Daniel O'Day took the helm as Gilead's chairman and chief executive officer, succeeding John F. Milligan, Ph.D., who stepped down after a 28-year career with the company. Mr. O'Day previously served as CEO of Roche Pharmaceuticals, a position he held since 2012, and prior to that led Roche Diagnostics. His career spans three decades of leadership roles across North America, Asia Pacific and Europe.
In other recent executive moves, Gilead appointed Johanna Mercier as its new chief commercial officer, joining the senior leadership team on July 1, and succeeding Laura Hamill, who is departing from Gilead after less than a year in the role.
Also, Robin Washington, executive vice president and chief financial officer, plans to retire from her role, effective March 1,2020, and Alessandro Riva, MD, executive vice president, Oncology Therapeutics, has decided to leave the company to pursue another opportunity. The company has yet to name successors for these two roles.
Updates to Gilead's HIV and liver diseases programs include approvals in China of Harvoni for the treatment of HCV genotype 1-6 infection, Vemlidy for the treatment of chronic HBV infection, and Descovy for the treatment of HIV-1 infection. Also, findings from two studies support the further development of GS-6207, a first-in-class, investigational capsid inhibitor, which may represent a novel approach to HIV treatment due to its long-acting characteristics and potent antiviral activity seen in vitro.
However, recent results from a Phase III study evaluating the safety and efficacy of selonsertib, an investigational, once daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), for patients with bridging fibrosis due to nonalcoholic steatohepatitis (NASH), did not meet its primary endpoint of improvement in fibrosis without worsening of NASH.
Gilead's oncology and cell therapy programs recently achieved promising study results from a Phase I/II study evaluating KTEX19, an investigational CD19 chimeric antigen receptor T cell therapy, in relapsed or refractory acute lymphoblastic leukemia. With a median follow-up of 15 months following a single infusion of KTE-X19, 69% of patients achieved complete tumor remission, and the rate of undetectable minimal residual disease in patients who achieved complete tumor remission was 100%.
Also, two-year efficacy and safety data of Yescarta in patients with refractory large B-cell lymphoma, showed 39% of patients were in an ongoing response with a median follow up of 27 months.
Additionally, results from an ongoing Phase III study of filgotinib, an investigational, oral, selective JAK1 inhibitor, in moderate-to-severe active rheumatoid arthritis, achieved its primary endpoint of patients achieving an American College of Rheumatology 20 percent response (ACR20) at Week 24. The proportion of patients achieving the primary endpoint was significantly higher for filgotinib 200 mg plus MTX and filgotinib 100 mg plus MTX compared with MTX alone.
Lastly, a Phase II study of filgotinib in severe active ankylosing spondylitis (AS) achieved its primary endpoint of significantly greater improvements in AS Disease Activity Score at Week 12, with a mean change from baseline of -1.5 versus -0.6 for those treated with placebo. More patients receiving filgotinib also achieved an ASAS20 response compared to those treated with placebo.
In its most recent deal, Gilead will pay Nurix Therapeutics $45 million up front and as much as $2.3 billion in milestones under a global strategic collaboration to develop and commercialize a pipeline of innovative targeted protein degradation drugs for cancer and other challenging diseases. Dysregulated and/or mutated proteins play a central role in the development and progression of many human diseases. Nurix's technology platform is focused on the manipulation of the ubiquitin system and its component E3 ligases, the key enzymes responsible for controlling protein levels in human cells.
Under an alliance with Agenus, Inc. focused on the development and commercialization of novel immuno-oncology therapies, Agenus will receive $150 million upfront including $30 million equity investment, and the agreement also includes approximately $1.7 billion in potential milestones.
A strategic collaboration with Scholar Rock Holding Corp. aims to discover and develop highly specific inhibitors of transforming growth factor beta activation for the treatment of fibrotic diseases. Scholar Rock will receive $80 million upfront in payments, including the purchase of Scholar Rock stock, and the company is eligible to receive up to an additional $1.4 billion in potential payments across three programs.
Moreover, a global strategic collaboration with Tango Therapeutics aims to develop and commercialize a pipeline of innovative targeted immuno-oncology treatments. Tango will receive $50 million upfront and is eligible to receive approximately $1.7 billion in additional payments across all programs.
Finally, Gilead is not giving up on nonalcoholic steatohepatitis (NASH) and has partnered with several companies to help advance its efforts. Gilead and Novo Nordisk are collaborating on a clinical trial combining compounds from their respective pipelines in NASH. The trial will combine Novo Nordisk's semaglutide (GLP-1 analogue) and Gilead's cilofexor (FXR agonist) and firsocostat (ACC inhibitor). The companies are also exploring the potential to collaborate on preclinical research to advance understanding of the disease.
Under a licensing and collaboration deal withYuhan Corp. to develop novel NASH candidates, Gilead acquired global rights to small molecules against two targets for $15 million upfront and up to an additional $770 million in potential milestones.
Lastly, Gilead and insitro partnered to discover and develop NASH therapies leveraging insitro's Human (ISH) platform to create disease models for NASH and discover targets that have an influence on clinical progression and regression of the disease. The insitro Human (ISH) platform applies machine learning, human genetics and functional genomics to generate and optimize unique models to drive discovery and development. Gilead can advance up to five targets identified through this collaboration.
Caption: Truvada sales fell, but were offset by Gilead's other HIV medicine, Genvoya, which grew 26% during the year.
Headquarters: London, UK
HEADCOUNT: 64,400 YEAR ESTABLISHED: 1999 REVENUES: $22,090 (-2%) NET INCOME: $2,050 (-29%) R&D: $5,932 (+3%)
DRUGS APPROVED DRUG INDICATION Lumoxiti Leukaemia, hairy cell (HCL) Lokelma Hyperkalaemia DRUGS FILED DRUG INDICATION PT010 COPD PHASE III DRUG INDICATION DS-8201 Breast cancer Tezepelumab Asthma Tremelimumab Non-small cell lung cancer (NSCLC), Head & neck cancers, Bladder cancer, Hepa toma, liver cancer, Small cell lung cancer (SCLC) Savolitinib Renal cell carcinoma (RCC) Selumetinib Other neurological indications Zemfirza Glioblastoma multiforme, Ovarian cancer AZD4547 Non-small cell lung cancer (NSCLC) BHV3241 Other neurological indications, Parkinson's disease Tralokinumab Eczema/Dermatitis Anifrolumab Systemic lupus erythematosus (SLE) Brazikumab Crohn's disease PT001 Asthma PT005 COAD/COPD GemRIS Bladder cancer MEDI8897 RSV infections AZD3759 Non-small cell lung cancer (NSCLC) FKB-238 Non-small cell lung cancer (NSCLC) SAIT101 Non-Hodgkin lymphoma (NHL) PT027 Asthma EARLY RESEARCH PROJECTS DRUG INDICATION AZD0156 solid tumors AZD4573 hematological malignancies AZD4635 solid tumors AZD9496 breast cancer Imfinzi + dabrafenib + trametinib melanoma Imfinzi + azacitidine myelodysplastic syndrome MEDI0562 solid tumors MEDI3726 prostate cancer MEDI7247 hematological malignancies adavosertib solid tumors oleclumab solid tumors AZD4831 heart failure AZD9977 CV disease MEDI7219 type-2 diabetes AZD1402 asthma MEDI3506 COPD AZD0284 psoriasis MEDI0700 systemic lupus erythematosus MEDI1814 Alzheimer's disease MEDI7352 osteoarthritis pain AZD5634 cystic fibrosis
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Faslodex breast cancer 2019 Byetta diabetes 2020 Onglyza diabetes 2023
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Symbicort asthma $2,561 -9% Crestor cholesterol $1,433 -39% Nexium acid reflux $1,702 -13% Brilinta antiplatelet $1,321 22% Farxiga type 2 diabetes $1,316 29% Tagrisso lung cancer $1,860 95% Pulmicort asthma $1,286 9% Faslodex breast cancer $1,028 9% Zoladex prostate cancer $752 2% Lopressor hypertension $654 1%
While AstraZeneca's total revenue for 2018 was off 2% ($22.1 bn) compared to last year, product sales were actually up 4%, climbing to $21.0 billion. The UK-based pharma major also ended the year on a high note, with a strong performance in the fourth quarter, including product sales growth of 5% and total revenue growth of 11%.
Product sales growth for the year can be attributed to the strong performance of new medicines (+81%) and the sustained strength of emerging markets (+12%), particularly China sales, which were up by 28% for the year. Oncology sales increased by 50% with Tagrisso and Lynparza each doubling in sales, along with promising performance from Imfinzi. Asthma drug Fasenra sales reached $297 million in its first hill launch year.
Looking further into AstraZeneca's oncology performance, Tagrisso sales of $1.8 billion represented growth of 95%. Based on its performance in 2018, AstraZeneca anticipates it to be its biggest-selling medicine in 2019. Lynparza sales of $647 million grew 118%, driven by expanded use in the treatment of ovarian cancer and the medicine's first approvals for use in the treatment of breast cancer. Imfinzi sales of $633 million grew from $19 million the year before, reflecting ongoing launches.
Also in oncology news, AstraZeneca strengthened its development and commercialization collaboration with Innate Pharma in October 2018. The agreement extension enriched AstraZeneca's immuno-oncology portfolio with preclinical and clinical assets. It obtained full oncology rights to the first-in-class humanized anti-NKG2A antibody, monalizumab. It also gained option rights to IPH5201, an antibody targeting CD39, as well as four preclinical molecules from Innate Pharma's pipeline. In addition, Innate licensed the U.S. and EU commercial rights to recently FDA-approved cancer drug Lumoxiti, which was launched in the U.S. in the fourth quarter.
On the divestment front, AstraZeneca sold a few pieces of its portfolio at the end of the year to sharpen its focus in oncology. In November, it completed an agreement to divest the prescription medicine rights to Nexium in Europe, as well as the global rights (excluding the U.S. and Japan) to Vimovo, to Griinenthal. AstraZeneca received payments of $700 million for Nexium and $115 million for Vimovo. During the same month AstraZeneca struck a $1.5 billion deal with Sobi for the rights to its infant drug Synagis. In December, it completed an agreement with Covis Pharma to sell its rights to asthma medicine Alvesco, and nasal relief drugs Omnaris and Zetonna, for $350 million.
DRUG DISCOVERY TIE-UPS
Medlmmune, the global biologics research and development arm of AstraZeneca, entered an exclusive license agreement with Compugen, a provider of predictive discovery and development of first-in-class therapeutics for cancer immunotherapy, for the development of bi-specific and multi-specific immuno-oncology antibody products. Compugen is providing an exclusive license to Medlmmune for the development of bi-specific and multi-specific antibody products derived from a Compugen pipeline program. Medlmmune has the right to create multiple products under this license and will be solely responsible for all research, development and commercial activities under the agreement.
In other discovery news, AstraZeneca adopted Horizon Discovery's Edit-R crRNA libraries as part of its initiative to establish a functional genomics discovery platform. AstraZeneca also joined the Genomics Discovery Initiative (GDI), a collaborative functional genomics screening community facilitated by Horizon. AstraZeneca has been evaluating Horizon's Edit-R human whole genome crRNA library for gene knockout since late 2017, and added the company's platform of arrayed synthetic crRNA libraries for CRISPR-mediated transcriptional activation (CRISPRa).The libraries offer a tool for functional genomic screens in drug discovery, providing deeper insight into biological mechanisms for the purpose of understanding disease progression, host-pathogen relationships, drug interactions, and pathway analysis.
Also, Bicycle Therapeutics is expanding its collaboration with AstraZeneca to include additional targets in respiratory and cardio-metabolic diseases. The original collaboration was signed in late 2016 and with the expansion has a potential value in excess of $1 billion. Under the terms of the collaboration, Bicycle is responsible for identifying targets for an undisclosed number of respiratory, cardiovascular and metabolic diseases specified by AstraZeneca, while AstraZeneca is responsible for further development and product commercialization.
Lastly, Ionis Pharmaceuticals licensed its Generation 2.5 IONIS-AZ5-2.5 to AstraZeneca. IONIS-AZ5-2.5 is an antisense drug designed to inhibit an undisclosed target to treat a genetically associated form of kidney disease. Astra-Zeneca is responsible for developing and commercializing IONISAZ5-2.5.
AstraZeneca entered a couple clinical collaborations during the year as well. With Bavarian Nordic it formed a new collaboration to investigate CV301, the company's targeted immunotherapy candidate, and durvalumab (IMFINZITM), AstraZeneca's PDL1 inhibitor, in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic cancers. Also, Syndax Pharmaceuticals entered a clinical collaboration with AstraZeneca to evaluate the safety and efficacy of durvalumab in combination with SNDX-6352, Syndax's monoclonal antibody inhibitor of Colony-Stimulating Factor 1 Receptor (CSF1R), across a variety of solid tumors.
Caption: AstraZeneca's R&D site in China. Sales in the country were up 28% for the year. (Courtesy AstraZeneca)
Headquarters: Leverkusen, Germany
HEADCOUNT: 116,998 YEAR ESTABLISHED: 1971 REVENUES: $45,278 (+13%) PHARMA REVENUES: $19,154 (-1%) NET INCOME: $1,934 (-77%) R&D: $6,000 (+16%)
DRUGS APPROVED DRUG INDICATION Jivi Haemophilia A Vitrakvi Solid tumor indications DRUGS FILED DRUG INDICATION Darolutamide Prostate cancer PHASE III DRUG INDICATION Finerenone Diabetic nephropathy Vericiguat Congestive heart failure (CHF) Molidustat Anaemia in chronic kidney disease (CKD) (dialysis), Entinostat Breast cancer Staxyn Erectile dysfunction Vilaprisan Uterine fibroids LMTX Alzheimer's disease, Dementia, frontotemporal MQB-015 Onychomycosis EARLY RESEARCH PROJECTS DRUG INDICATION TRK Inhibitor cancer Rogarantinib cancer PTEFb Inhibitor cancer ATR Inhibitor cancer DHODH Inhibitor cancer Copanlisib cancer Regorafenib cancer Anetumab Ravtansine cancer CD22-Targeted Thorium Conjugate cancer MSLN-Targeted Thorium Conjugate cancer PSMA-Targeted Thorium Conjugate cancer CEACAM6 fb Antibody cancer ILDR2 fb Antibody cancer FXIa Inhibitor anticoagulation Anti-FXI Antibody anticoagulation Vasopressin Receptor Antagonist heart failure sGC Activator 2 Pulmonary hypertension P2X3 Antagonist 1 endometriosis P2X3 Antagonist 2 endometriosis P2X4 Antagonist endometriosis IRAK4 Inhibitor 1 endometriosis FVIII Gene Therapy hemophilia sGC Activator 3 acute respiratory distress syndrome PEG-ADM Inhale acute respiratory distress syndrome TASK Channel Blocker 2 obstructive sleep apnea IRAK4 Inhibitor 2 rheumatoid arthritis sGC Activator 1 chronic kidney disease Vasopressin V1a Receptor Antagonist chronic kidney disease
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Zetia hyperlipidaemia 2019 Nexavar renal cell carcinoma 2020 Xofigo prostate cancer 2022
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Xarelto atrial fibrillation $3,689 17% Eylea macular degeneration $2,581 21% Mirena women's health $1,350 6% Kogenate hemophilia $1,010 -8% Nexavar oncolgy $841 -11% Yasmin contraception $755 3% Precose diabetes $733 16% Adalat hypertension $722 -1% Asprin Cardio Myocardial infarction prophylaxis $658 0% Betaferon multiple sclerosis $643 -13%
After Bayer made the mega $63 billion deal for Monsanto, turning it into the world's largest agro-chemical maker and seed producer, it was forced to make some major overhauls.
The company announced at the end of the year it would be axing 12,000 jobs throughout the crop science, pharma and consumer units. Of the job losses, roughly 1,250 were in pharma with 350 related directly to a new manufacturing facility in Wuppertal, Germany that the company will not use, focusing all recombinant factor VIII production at its Berkeley, CA site instead.
In addition, as this issue went to press Bayer had already sold off the iconic Coppertone skin care brand and was still looking for a buyer for the Dr. Scholl's foot care brand and its animal health unit. China's Fosun International, parent of Fosun Pharma, was on the hunt for the animal health business, looking to partner with private equity to make an offer--the sale could be worth nearly $8 billion if it goes down.
With all the shake-ups, pharma sales were off by just one percent for the year ($19.2 bn) when factoring in exchange rates. Growth in pharma is being driven primarily driven by its top selling drug Xarelto and Eylea, with several promising late-stage R&D pipeline candidates. Sales of the oral anticoagulant Xarelto were up 17% and eye medicine Eylea climbed 21% while cancer drugs Stivarga and Xofigo, and the pulmonary hypertension treatment Adempas advanced by 13.5%.
Looking ahead to the eventual loss of exclusivity for Xarelto and Eylea, Bayer is amping up its oncology pipeline. At the end of 2017 it made a deal with Loxo Oncology to develop and commercialize larotrectinib and LOXO-195, Loxo Oncology's franchise of highly selective TRK inhibitors for patients with TRK fusion cancers. A year later, in November 2018, FDA approved larotrectinib, which is now sold under the brand name Vitrakvi.
More good news came on the cancer treatment front when Bayer reported positive results of the Phase III study of darolutamide, a novel androgen receptor antagonist of for the oral treatment of prostate cancer that is being developed jointly by Bayer and the Finnish biopharmaceutical company Orion Corporation.
Research and development of new immunotherapy approaches in oncology continued through a partnership with Compugen Ltd., a company focused on predictive discovery and development of therapeutics for cancer immunotherapy. COM902, its lead anti-TIGIT antibody, advanced into manufacturing for an investigational new drug (IND) application that was anticipated in 2019. The companies entered into a process development and manufacturing service agreement to produce COM902 for future use in clinical trials.
With the University of Texas MD Anderson Cancer Center it signed a five-year collaboration agreement to accelerate the development of novel targeted treatments based on patient or tumor characteristics for which current therapies have not shown satisfactory clinical efficacy. Bayer will contribute early stage as well as clinical assets from its development pipeline for further clinical development at MD Anderson Cancer Center. The MD Anderson Cancer Center will bring in its translational and clinical expertise to help accelerate ongoing and future clinical trials.
Bayer entered a few collaborations during the year outside the cancer realm. With the Broad Institute of MIT and Harvard, Bayer launched the joint Precision Cardiology Laboratory, which will pursue novel scientific insights to enable the development of new therapies for patients with cardiovascular diseases such as heart failure. Heart failure--a general diagnosis given when the heart doesn't pump effectively--is a composite of multiple factors, and as such requires new tools and methods to gain deeper knowledge to benefit patients. The scientists at the joint laboratory will combine Broad Institute's methods for basic science discovery such as single cell sequencing and clinical expertise with Bayer's long experience in drug development to discover new potential therapeutics.
Furthermore, Bayer and Haplogen GmbH, a Vienna-based biotechnology company, entered into a multi-year research collaboration agreement to identify new drug candidates for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD). COPD is a common and heterogeneous respiratory disease that causes breathlessness and predisposes to exacerbations and serious illness. Respiratory viral infections are one frequent cause of COPD exacerbations. One possible treatment approach for COPD exacerbations is to disrupt the multiplication of the responsible virus by inhibiting its replication. The goal of the research alliance is to develop new antiviral compounds addressing the high unmet medical need in reducing COPD exacerbations.
At the start of 2019, Bayer and Kyoto University agreed on a strategic research alliance to jointly identify new drug targets for the treatment of pulmonary diseases such as idiopathic pulmonary fibrosis. The goal of the research alliance is to identify specific targets and pathways that are causing the disease and to discover new treatments to modulate these pathways and prevent further lung functions decline. Bayer has an option for the exclusive use of the collaboration results.
Caption: Bayer continues to undergo major restructuring after its $63 billion purchase of Monsanto.
Headquarters: Petach Tivka, Israel
HEADCOUNT: 42,535 YEAR ESTABLISHED: 1901 REVENUES: $18,854 (-16%) LOSS: $2,472 (NM) R&D: $1,213 (-32%)
DRUGS APPROVED DRUG INDICATION Ajovy migraine DRUGS FILED DRUG INDICATION Eptinezumab migraine PHASE III DRUG INDICATION Fasinumab Osteoarthritis, chronic pain Multikine Head & neck cancers NeuVax Breast cancer TV-46000 Schizophrenia EARLY RESEARCH PROJECTS DRUG INDICATION TV-46046 contraception Omacetaxine + Cytarabine and Idarubicin acute myeloid leukemia Arsenic trioxide chronic myelogenous leukemia Metronidazole bacterial vaginosis
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Treanda Leukaemia, 2022 chronic lymphocytic
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Copaxone Relapsing-Remitting MS $2,366 -38% Bendeka Leukaemia, chronic lymphocytic Non-Hodgkin lymphoma $642 -2% Methylphenidate Hydrochloride Attention deficit disorder/hyperactivity (ADD/ADHD) $481 -29% ProAir HFA Asthma $397 -21% Austedo Huntington's disease, Tardive dyskinesia $204 750% Methylphenidate Hydrochloride Attention deficit disorder/hyperactivity ADD/ADHD) $192 -58% QVAR RediHaler Asthma $190 n/a Daptomycin Skin infections, Endocarditis $167 45% Metoprolol Succinate Hypertension $132 -13% Sildenafil Citrate Erectile dysfunction $122 205%
Teva's revenues in 2018 were $18.8 billion, a decrease of 16% compared to 2017, mainly due to generic competition to multiple sclerosis drug Copaxone, a decline in revenues in the U.S. generics business and loss of revenues following the divestment of products and discontinuation of activities, all of which are part of a global restructuring effort announced by the Israeli generics giant at the end of 2017. In terms of sales, the beginning of 2019 didn't show signs of hope. Revenues of $4.3 billion in the first quarter of 2019 continued the downward trend, marking a decrease of 15%.
At the time its plans were unveiled, Teva said it would undergo a major overhaul of its operations, restructuring in an effort to significantly reduce costs and simplify its organization, as it faced $35 billion of acquisition-related debt stemming from the $40.5 billion purchase of Allergan in 2016. The plan called for cutting $3 billion in costs by the end of 2019, including the elimination of 14,000 positions globally, more than 25% of Teva's total workforce. The majority of cuts occurred in 2018, but have carried over into this year as well.
Teva said it plans to pump up its generics portfolio globally, specifically in the U.S., through price adjustments and/or product discontinuation. It also continues to accelerate the restructuring of its manufacturing and supply network, including the closures or divestments of a significant number of manufacturing plants in the U.S., Europe, Israel and growth markets.
Teva said it will also close or divest a significant number of R&D facilities, headquarters and other office locations across all geographies. The company will also review all R&D programs in generics and specialty, to prioritize core projects and terminate other, non-core assets.
In one instance, Teva and Procter & Gamble agreed to terminate the PGT Healthcare partnership that the two companies established in 2011 to market OTC medicines. PGT Healthcare had grown into a significant presence in over 50 countries, mainly in Europe and Asia, using market-leading brands such as Vick's and ratiopharm. However after nearly seven years working together, the companies concluded that their priorities and strategies were no longer closely aligned. Each company took back its own brand and product assets to re-establish independent OTC businesses.
As part of the global restructuring process, during the year Teva unveiled plans to consolidate its North America Commercial business into New Jersey. Teva will establish its North America headquarters in Parsippany-Troy Hills, including more than 1,000 jobs and the transfer and creation of more than 800 positions. Teva accepted an offer of a 10-year and $40 million in tax savings incentives from the NJ Economic Development Authority to move forward with the plan. The moved marked yet another step forward and in-line with Teva's global restructuring effort to drive savings, restore financial security and stabilize its business by reducing the number of sites it operates to unify and simplify the organization, as well as improve productivity and efficiencies.
In 2018, Teva and Insilico Biotechnology entered an agreement to apply Insilico's technology for predictive biomanufacturing to create and implement more efficient production processes of Teva's biopharmaceutical therapeutics. Insilico's solutions for predictive bio-manufacturing are one of the key technologies to convert this value into higher quality therapies and to bring them faster to market. Insilico's Digital Twins of biopharmaceutical production processes employ metabolic models of producer organisms in combination with flexible process models and artificial intelligence to create optimized production processes by computational simulations. The collaboration will run for three years and will be based at Insilico's sites in Stuttgart, Germany and at Teva's West Chester, PA, location.
In another deal to bolster its biomanufacturing operations, Teva teamed up with Genedata, a provider of bioinformatics enterprise software, to use its workflow platform to streamline the identification, engineering, and characterization of novel biopharmaceuticals drugs. Teva will use Genedata Biologics as their backbone system across their antibody discovery operations. In addition, the platform will enable a thorough assessment of a drug candidate's developability profile and facilitate handovers to the Teva development and manufacturing organization.
In September 2018, Teva received approval from the FDA for its AJOVY (fremanezumab-vfrm) injection for the preventive treatment of migraine in adults. AJOVY, a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocksits binding to the receptor, is the first and only anti-CGRP treatment for the prevention of migraine.
Teva also received approval from the FDA at the end of the year for its ProAir Digihaler (albuterol sulfate 117 meg) inhalation powder, the first and only digital inhaler with built-in sensors which connects to a companion mobile application and provides inhaler use information to people with asthma and COPD. ProAir Digihaler is indicated for the treatment or prevention of bronchospasm in patients aged four years and older with reversible obstructive airway disease, and for prevention of exercise-induced bronchospasm (EIB) in patients aged four years and older. The device contains built-in sensors that detect when the inhaler is used and measure inspiratory flow. This inhaler-use data is then sent to the companion mobile app using Bluetooth Wireless Technology so patients can review their data over time, and if desired, share it with their healthcare professionals.
16 NOVO NORDISK
Headquarters: Bagsvaerd, Denmark
HEADCOUNT: 43,202 YEAR ESTABLISHED: 1989 REVENUES: $17,127 (flat) NET INCOME: $5,916 (+1%) R&D: $2,267 (+6%)
DRUGS FILED DRUG INDICATION Semaglutide Oral Diabetes, type II (maturity onset), General cardiovascular indications PHASE III DRUG INDICATION Somapacitan Short stature in children, Adult growth hormone deficiency Semaglutide Transdermal Diabetes, type II (maturity onset), Obesity EARLY RESEARCH PROJECTS DRUG INDICATION OG2023SC type 2 diabetes LAISema diabetes PYY 1562 obesity GG-co-agonist 1177 obesity Tri-agonist 1706 obesity PYY 1875 obesity
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Levemir diabetes 2019 Tretten Factor XIII deficiency 2021 Victoza diabetes 2023
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Victoza diabetes $3,857 10% NovoRapid diabetes $2,974 -2% Levemir diabetes $1,774 -17% NovoMix 30 diabetes $1,503 -4% Human insulin & devices diabetes $1,469 -4% Tresiba diabetes $1,274 14% NovoSeven Haemophilia A, B $1,249 -11% Norditropin SimpleXx Short stature in children $1,083 7% Saxenda obesity $613 58% Insulin Analogues diabetes $508 10%
Revenue was flat for Novo Nordisk in 2018 at $17.1 billion. The Danish firms sells medicines mainly in diabetes, which accounted for almost $15 billion worth of group sales. Victoza again was the companies top seller, raking in $3.9 billion, a 10% growth from the year before. The newly launched diabetes medicine Tresiba performed well, climbing 14% to $1.2 billion. However, the fastest grower in the portfolio was the new obesity drug Saxenda--it's $613 million in sales marked a 58% growth.
During the year, Novo Nordisk continued to broaden its diabetes portfolio and pipeline. In February 2018, it launched Ozempic, a new once-weekly GLP-1, in the U.S. The type 2 diabetes drug has now been launched in 11 countries in Europe and North America. In November, Novo Nordisk completed the Phase Ilia PIONEER program for oral semaglutide, a new once-daily GLP1 tablet also for people with type 2 diabetes. Novo Nordisk submitted the oral semaglutide file around the end of first quarter 2019 to FDA and requested priority review.
Also, Novo Nordisk struck a deal with Evotec AG to discover and develop novel small molecule therapies to treat diabetes and obesity, as well as co-morbidities such as nonalcoholic steatohepatitis (NASH), cardiovascular diseases, and diabetic kidney disease. Evotec will apply its drug discovery platform to design novel, safe and efficacious products. Once suitable preclinical candidates are selected, Novo Nordisk will use Evotec's INDiGO platform to move through preclinical studies to enter IND registration.
In an effort to grow the bio side of its business--group biopharmaceuticals sales decreased by 5% during the year to $2.8 billion--Novo Nordisk eliminated approximately 250 jobs in the U.S.
The company said it made the move as it continues to witness more modest growth in its diabetes franchises in recent years as a result of pricing pressures in the U.S., which accounts for approximately half of its revenue. One hundred of the staff reductions are from back-office positions in the company's U.S. headquarters in Princeton, NJ, and the remaining 150 are among diabetes treatment support positions. The company previously announced plans to cut 400 staff in Denmark and China, also as part of an effort to focus on investments in biologics and technology innovation.
Novo Nordisk also expanded its biopharm business with an agreement to acquire the U.S. and Canadian rights to Macrilen, the first FDA-approved oral growth hormone receptor indicated for the diagnosis of Adult Growth Hormone Deficiency (AGHD), a rare endocrine disorder, from Strongbridge Biopharma.
Expanding its capabilities in biotechnology innovation, Novo Nordisk purchased Berkeley Lights'Beacon Optofluidic platform to accelerate workflows in cell line development and to use the platform for future protein and antibody discovery.
Headquarters: Osaka, Japan
HEADCOUNT: 27,230 YEAR ESTABLISHED: 1781 REVENUES: $15,967 (+2%) NET INCOME: $1,684 (+62%) R&D: $2,935 (+4%)
DRUGS APPROVED DRUG INDICATION Takhzyro Hereditary angioedema Motegrity Constipation PHASE III DRUG INDICATION TAK-003 Dengue fever prophylaxis SHP655 Thrombocytopaenic purpura, thrombotic (TTP) TAK-609 Hunter syndrome TAK-721 Eosinophilic oesophagitis Camvia CMV infections SHP647 Ulcerative colitis, Crohn's disease TAK-640 Conjunctivitis, infectious Cenicriviroc Nonalcoholic steatohepatitis (NASH) Tedopi Non-small cell lung cancer (NSCLC) Maralixibat Cholestasis EARLY RESEARCH PROJECTS DRUG INDICATION TAK-573 relapsed refractory multiple myeloma TAK-164 gastrointestinal malignancies TAK-981 multiple cancers TAK-951 nausea and vomiting Kuma062 celiac disease TAK-018 Chron's disease TAK-681 short bowel syndrome TAK-671 acute pancreatitis TAK-531 Hunter syndrome TAK-653 treatment-resistant depression TAK-418 Kabuki syndrome MEDI-1341 Parkinson's disease VWE-120101 Huntingtion's disease TAK-426 Zika vaccine
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Uloric gout 2019 Dexilant acid reflux 2020
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Entyvio ulcerative colitis, Crohn's disease $2,428 34% Velcade multiple myeloma $953 -7% Leuprorelin prostate cancer, breast cancer, endometriosis $790 -1% Azliva hypertension $639 11% Dexilant acid reflux $624 5% Ninlaro multiple myeloma $561 34%
The largest, and only mega-deal of 2018 was Takeda's $62 billion acquisition of Dublin, Ireland-based Shire. The deal, announced in May and finalized in January 2019, propels Takeda into the top 10 pharma companies and is one of the largest overseas acquisition deals ever in Japanese history. Projected sales for 2019 are in the $30 billion range.
With the Japanese pharma market lagging, Takeda's purchase gives it an expanded geographic footprint, scale, and most importantly, a bigger foothold in the U.S. To offset pricing pressures in the U.S., the deal bolsters Takeda's portfolio of rare disease therapeutics, currently viewed as an under-saturated market of high value due to regulatory incentives and high drug prices.
In addition to creating leading positions in rare diseases and plasma-derived therapies, complementing strengths in oncology and vaccines, the deal bolsters its portfolios in gastroenterology and neuroscience as well.
While the Shire deal was being worked out, in September Takeda unveiled plans to move its U.S. headquarters and 1,000 employees from the suburbs of Chicago to the Boston area, where most of Shire's operations existed--3,000 of its employees in Lexington and Cambridge. The Japanese pharma giant is now the largest biopharma firm in the Boston area, which has overtaken rival California as the number one biotech hub in the world.
Takeda continued to diversify its cancer research activities with collaborations in immuno-oncology, an area of key strategic focus for the company. An alliance with Memorial Sloan Kettering aims to discover and develop novel CAR-T products for multiple myeloma, acute myeloid leukemia and solid tumor indications.
It also exercised an option under a research collaboration with Noile-Immune Biotech, licensing NIB-102 and NIB-103 for the treatment of various solid tumor indications, and will co-develop these CAR-T cell therapies with Noile using their "Prime" CAR-T platform. The company plans to gain regulatory approval for human testing of NIB-102 by the end of this year.
Through collaboration with external partners and the newly established translational cell therapy engine, Takeda is laying the foundation to deliver a rich pipeline of early-stage assets in the coming years.
Headquarters: Dublin, Ireland
HEADCOUNT: 16,900 YEAR ESTABLISHED: 2015 REVENUES: $15,787 (-1%) LOSS: $5,086 (NM) R&D: $2,266 (+8%)
DRUGS FILED DRUG INDICATION Ubrogepant Migraine Cabazitaxel Injection Prostate cancer PHASE III DRUG INDICATION Rapastinel Depression Atogepant Migraine Bimatoprost SR Glaucoma Abicipar Wet age-related macular degeneration (AMD) Relamorelin Gastroparesis Cenicriviroc Nonalcoholic steatohepatitis (NASH) ABP798 Non-Hodgkin lymphoma (NHL), Arthritis, rheumatoid Vitaros Erectile dysfunction Zydena General cardiovascular indications Vadadustat Anaemia in chronic kidney disease (CKD) (non-dialysis) ATM-AVI Gram negative infections Qapzola Bladder cancer Presbysol Refractive error, presbyopia Brazikumab Crohn's disease EARLY RESEARCH PROJECTS DRUG INDICATION Dalbavancin Bacterial Infections AGN-151587 Leber Congenital Amaurosis 10 RST-001 Advanced Retinitis Pigmentosa AGN-241751 Major Depressive Disorder ABI-M201 Ulcerative Colitis Ceftaroline Fosamil Hematogenously Acquired Staphylococcus
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Botox Blepharospasm 2020 Bystolic Hypertension 2021 Combigan Glaucoma 2023
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Botox Therapeutics chronic migraine, overactive bladder $3,577 13% Restasis dry eye $1,262 -14% Linzess irritable bowel syndrome $785 9% Lumigan ocular hypertension $684 -1% Bystolic hypertension $586 -5%
Just as this issue was getting ready to fly, AbbVie shook up the pharma world with its $63 billion acquisition of Allergan. The Botox-maker, and biggest name in medical aesthetics, helps AbbVie diversify a portfolio that includes the world's best-selling drug, Humira, which soon faces generic competition in Europe. The combined company will consist of several franchises with leadership positions across immunology, hematologic oncology, medical aesthetics, neuroscience, women's health, eye care and virology.
The mega-deal comes after Allergan tried to become more efficient by reducing costs and streamlining operations. At the beginning of 2018 it unveiled a restructuring plan that called for the elimination of 1,000 jobs as part of the effort. It also recently unloaded its generics business toTeva for $40 billion in 2016.
In September 2018 Allergan also divested products in its dermatology unit to Almirall, S.A. for $550 million. The products include Aczone, Tazorac, Azelex and Cordran Tape, as well as sarecycline, a new chemical entity currently under FDA review for the treatment of acne.
Allergan recorded $15.7 billion in revenues in 2018, a drop of 1% from the year before. Its top selling product is Botox, a cosmetic filler with pharmaceutical indications for chronic migraine and overactive bladder, which grew 13% with $3.5 billion in sales. The year wasn't so good for Allergan's other top seller, dry eye drug Restasis, which saw its revenue drop 14% to $1.2 billion.
A major highlight during the year saw Allergan and Amgen together win European approval for MVASI (biosimilar bevacizumab). MVASI is the first biosimilar bevacizumab approved by the EC and is approved for the treatment of certain types of cancers, including in combination with chemotherapy or other therapies for metastatic carcinoma of the colon or rectum, metastatic breast cancer, non-squamous non-small cell lung cancer, renal cell cancer, ovarian, fallopian tube, or primary peritoneal cancer, or metastatic carcinoma of the cervix.
In September 2017, MVASI became the first anti-cancer biosimilar, as well as the first biosimilar bevacizumab, to be approved by the FDA. Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars.
In acquisition news, Allergan bolstered its medical aesthetics portfolio, specifically facial injectables, when it paid $195 million for Bonti, Inc., a clinical-stage biotech focused on novel, neurotoxin programs for aesthetic and therapeutic applications.
Headquarters: Summit, NJ
HEADCOUNT: 8,852 YEAR ESTABLISHED: 1986 REVENUES: $15,281 (+18%) NET INCOME: $4,046 (+38%) R&D: $5,673 (-4%)
DRUGS FILED DRUG INDICATION Luspatercept Thalassaemia, Myelodysplastic syndrome Ozanimod Relapsing-Remitting MS Fedratinib Myelofibrosis DRUGS IN PHASE III DRUG INDICATION Liso-cel Non-Hodgkin lymphoma ide-cel Multiple myeloma Tislelizumab Hepatoma, Non-small cell lung cancer, Oesophageal, Liver, Stomach, Bladder cancer, Small cell lung cancer CC-486 Myelodysplastic syndrome, Leukaemia, lymphomas Marizomib (IV) Glioblastoma multiforme PDA-001 Crohn's disease T Cell Therapy Solid tumor indications EARLY RESEARCH PROJECTS DRUG INDICATION CC-93269 relapsed/refractory mutiple myeloma GEM333 acute myeloid leukemia CC-90002 non-Hodgekin's lymphoma Avadomide diffuse large B-cell lymphoma CC-90010 non-Hodgekin's lymphoma CC-90011 solid tumors CC-90006 psoriasis
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Thalomid leprosy 2019 Revlimid Myelodysplastic syndrome 2022 Abraxane Breast cancer 2022
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Revlimid multiple myeloma, mantle cell lymphoma $9,685 18% Pomalyst multiple myeloma $2,040 26% Otezla psoriasis $1,608 26% Abraxane breast, lung, pancreatic cancer $1,062 7% Vidaza myelodysplastic syndrome $594 -5% Thalomid leprosy $114 -14%
The year 2019 had barely begun when on January 3, BMS said it was paying roughly $74 billion to acquire Celgene, creating a top 10 company and a leading specialty biopharma in the areas of cancer, inflammatory and immunologic disease and cardiovascular disease.
The combined company offers leading oncology franchises in both solid tumors and hematologic malignancies with Opdivo and Yervoy as well as Revlimid and Pomalyst; a top five immunology and inflammation franchise with Orencia and Otezla; and the number one cardiovascular franchise led by Eliquis. The portfolio will include nine products with more than $1 billion in annual sales and significant potential for growth in the core disease areas of oncology, immunology and inflammation and cardiovascular disease.
When the news was announced, near-term launch opportunities included six expected product launches: two in immunology and inflammation, TYK2 and ozanimod; and four in hematology, luspatercept, liso-cel (JCAR017), bb2121 and fedratinib.
Together, the company will also have expanded capabilities in small molecule design, biologics/synthetic biologics, protein homeostasis, antibody engineering and cell therapy.
In 2018, growth was driven by strong product sales including Revlimid, $9.6 billion, up 18%; Pomalyst, $2 billion, up 26%; Otezla, $1.6 billion, up 26%; and Abraxane, $1 billion, up 7%.
Early in 2018, Celgene acquired Impact Biomedicines and its fedratinib for myelofibrosis and polycythemia vera, for $7 billion.
Celgene also plans to open a Research Incubator and Collaboration Center offering entrepreneurs lab space, resources and support to scientists and companies with potentially transformational approaches to accelerate medical innovations. Set to open this year, the facility houses 16,000 sq.-ft. of shared and fully equipped lab facilities on its campus in Summit, NJ.
Celgene formed several R&D partnerships, including a long-term discovery and development deal to identify new therapeutics in oncology with Evotec leveraging its preclinical discovery platform. This includes a phenotypic screening platform with unique compound libraries and associated target de-convolution capabilities. Celgene entered another discovery tie-up with Evotec in the field of targeted protein degradation that will leverage Evotec's Ranomics platform to identify drug targets that are traditionally difficult to track. The platform applies proteomics and transcriptomics at industrial scale to profile and select promising drug candidates based on cell profiles.
Headquarters: Ingelheim, Germany
HEADCOUNT: 50,370 YEAR ESTABLISHED: 1817 REVENEUS: $20,014 (-3%) PHARMA REVENUES: $15,204 (flat) NET INCOME: $2,373 (NM) R&D: $3,619 (+3%)
DRUGS FILED DRUG INDICATION Empagliflozin & Linagliptin & Metformin XR Diabetes, type II (maturity onset) PHASE III DRUG INDICATION Volasertib Leukaemia, acute myeloid (AML) MOR208 Non-Hodgkin lymphoma (NHL) Bl 695502 Non-small cell lung cancer (NSCLC), Colorectal cancer Bl 655130 Ulcerative colitis, Psoriasis Capsaicin/ Diclofenac Pain, acute Inhaled Fentanyl Pulmonary fibrosis, idiopathic, General respiratory disorders EARLY RESEARCH PROJECTS DRUG INDICATION GLP1R/GCGR agonist cardiometabolic diseases Amylin analog cardiometabolic diseases EmpaLinaMet XR cardiometabolic diseases MRNA vaccine cancer PD-1 antibody cancer Cysteine protease inhibitor respiratory diseases Non-receptor tyrosin kinase inhibitor respiratory diseases IL36R antibody immunology Nuclear receptor antagonist immunology TRPC 4/5 inhibitor central nervous system diseases
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Aptivus HIV 2019 Spiriva COPD, asthma 2019 Pradaxa pulmonary embolism 2021
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Spiriva COPD, asthma $2,849 -11% Pradaxa atrial fibrillation $1,755 8% Trajenta type 2 diabetes $1,650 18% Jardiance type 2 diabetes $1,726 51% Ofev idiopathic pulmonary fibrosis $1,299 25% Micardis hypertension $942 -5% Glyxambi diabetes $493 143%
Boehringer Ingelheim ended 2018 with flat pharma sales of $15.2 billion. As in previous years, the respiratory medicine Spiriva achieved the highest sales contributions with $2.8 billion, but this was an 11% drop from the year before due mostly to patent expiry. All other major products in Boehringer's portfolio performed well. The anticoagulant Pradaxa was the next top seller with $1.8 billion in sales followed by type 2 diabetes drugs Jardiance, which grew 51% to $1.7 billion and Trajenta, which grew 18% to $1.6 billion. Rounding out the companies billion dollar performers was idiopathic pulmonary fibrosis treatment Ofev, which recorded $1.3 billion, up 25%.
In June 2018, Boehringer unveiled major investment plans on the biologics R&D front, pumping roughly $262 million into a new Biologicals Development Center (BDC) at the company's site in Biberach, Germany. The BDC is part of the company's long-term strategy to grow its biologics pipeline, specifically immune oncology and immunology. The company's share of new biologics has been consistently increasing over the past few years and has now reached 40%.
The BDC will integrate biologics analytical and process development as well as manufacturing for clinical studies into one unit, while at the same time increasing development capacity. Following a staggered launch beginning in 2020, the new building will be home to 500 employees.
The new BDC adds to a number of major recent investments in its global biopharmaceuticals network aimed at increasing mammalian cell culture capabilities. This includes a large scale biopharmaceutical facility in Vienna, Austria, a new biopharmaceutical facility in Shanghai, China, and the expansion of existing large scale biopharmaceutical capacities in Fremont, CA.
On the cancer research front, Boehringer and Vanderbilt University expanded an existing collaboration to develop anti-cancer compounds, and formed a collaboration with OSE Immunotherapeutics to jointly develop OSE-172, a cancer immunotherapy.
In terms of filings, FDA granted Fast Track to Boehringer's nintedanib for the treatment of systemic sclerosis with associated lung disease. In addition, positive results were reported from a Phase III study confirming that Cyltezo, the first biosimilar from Boehringer to be approved by FDA, is equivalent to Humira. This is the first U.S. study to investigate an interchangeability designation for an adalimumab biosimilar.
Headquarters: Cambridge, MA
HEADCOUNT: 7,800 YEAR ESTABLISHED: 2003 REVENUES: $13,453 (+10%) NET INCOME: $4,431 (+75%) R&D: $2,597 (+15%)
DRUGS APPROVED DRUG INDICATION Trogarzo HIV DRUGS FILED DRUG INDICATION Lusduna Diabetes I, II Vumerity Relapsing-Remitting MS (RRMS) DRUGS IN PHASE III DRUG INDICATION BIIB093 Stroke, acute, Cerebral oedema BIIB074 Pain, neuropathic Tofersen Amyotrophic lateral sclerosis BAN2401 Alzheimer's disease Elenbecestat Alzheimer's disease SB8 Non-small cell lung cancer EARLY RESEARCH PROJECTS DRUG INDICATION BIIB061 multiple sclerosis BIIB076 Alzheimer's disease BIIB078 amyotrophic lateral sclerosis BIIB080 Alzheimer's disease BIIB095 neuropathic pain BIIB110 spinal muscular atrophy
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Tecfidera multiple sclerosis $4,274 1% Avonex multiple sclerosis $1,915 -11% Tysabri multiple sclerosis $1,864 -6% Spinraza spinal muscular atrophy $1,724 95% Eticovo rheumatoid arthritis $485 31% Plegridy multiple sclerosis $448 -9%
A steady growth trajectory has Biogen up in the rankings this year. In addition to its flagship multiple sclerosis franchise, the continued global launch of spinal muscular atrophy drug Spinraza, which contributed $518 million in revenues in the first quarter, up 42%, is driving growth.
Biogen continues to diversify its pipeline in neuromuscular diseases and movement disorders, and, with the recent acquisition of Nightstar Therapeutics, specialty ophthalmology. By the end of 2020 the company expect results across its clinical programs in MS, progressive supranuclear palsy, ALS, Parkinson's, pain, cognitive impairment in schizophrenia, epilepsy, stroke, and lupus.
In June, Biogen completed the acquisition of Nightstar Therapeutics, a gene therapy company focused on adeno-associated virus (AAV) treatments for inherited retinal disorders, in a transaction valued at approximately $800 million. Biogen added two mid--to late-stage clinical assets as well as preclinical programs in ophthalmology. NST's lead asset is NSR-REP1 for the treatment of choroideremia, a rare, degenerative, X-linked inherited retinal disorder, which leads to blindness and has no approved treatments. NSR-RPGR is NST's second clinical program for X-linked retinitis pigmentosa, which is also a rare inherited retinal disease with no approved treatments.
Further investing in its biosimilar business, under an asset transfer deal with its collaboration partner Samsung BioLogics, assets of Samsung Bioepis were transferred to Biogen on November 7th for approximately $677 million. Samsung Bioepis was founded in 2012 as an 85:15 joint venture between Samsung BioLogics and Biogen. Last June Biogen raised its stake in Bioepis, increasing its ownership to 49.9 percent.
Under the successful alliance, Biogen became the first company in Europe with approved biosimilars referencing the three most prescribed anti-TNF biologic treatments, with the launch of IMRALDI, a biosimilar referencing Abbvie's Humira.
After evaluating its manufacturing strategy, in March, Biogen sold its large-scale biologics manufacturing operations in Hillerad, Denmark, to Fujifilm Corp. for up to $890 million. As part of the deal, Fujifilm will use the Hillerad site to produce commercial products for Biogen, such asTYSABRI, and other third-party products.
In unfortunate R&D news, the discontinuation of aducanumab for Alzheimer's disease was a big disappointment. Biogen and partner Eisai discontinued global Phase III trials after futility analysis indicated the trials were unlikely to meet their primary endpoint.
On the upside, Biogen is a few months away from expanding its MS franchise with Vumerity, which has an FDA target action date in 4Q19. Recent Phase III study results showed Vumerity significantly reduced disease activity in newly diagnosed relapsing multiple sclerosis patients.
To support research efforts in neurological diseases, an alliance with C4 Therapeutics will investigate the use of C4's protein degradation platform to develop new treatments for neurological conditions, such as Alzheimer's and Parkinson's. Biogen will pay C4 up to $415 million in upfront and potential milestones.
Additionally, Biogen paid $74 million upfront to Skyhawk for research services and an exclusive license to therapeutic candidates for multiple sclerosis, spinal muscular atrophy and other neurological diseases to be developed using SkySTAR platform, which offers a new approach to target neurological conditions using selective RNA-modulating small molecules.
Headquarters: Tokyo, Japan
HEADCOUNT: 16,243 YEAR ESTABLISHED: 2005 REVENUES: $11,781 (flat) NET INCOME: $2,249 (+22%) R&D: $1,882 (-6%)
DRUGS PENDING DRUG INDICATION Xospata relapsed, refractory acute myeloid leukemia PHASE III DRUG INDICATION IMAB362 Stomach cancer, Gastro-intestinal adeno carcinoma, Oesophageal cancer Enfortumab Vedotin Bladder cancer Crenolanib Gastro-intestinal stromal tumours (GIST), Leukaemia, acute myeloid (AML), Soft tissue sarcoma EARLY RESEARCH PROJECTS DRUG INDICATION ASP8374/PTZ-201 cancer ASP1948/PTZ-329 cancer ASP1951/PTZ-522 cancer ASP9801 cancer ASP0892 peanut allergy ASP3772 prevention of pneumococcal disease ASP0367/MA-0211 duchenne muscular dystrophy ASP1235/AGS62P1 acute myeloid leukemia MucoRice-CTB diarrhea prophylaxis
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Vesicare overactive bladder 2019 Myrbetriq overactive bladder 2022
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Xtandi prostate cancer $3,004 13% Prograf liver transplantation $1,431 -1% Myrbetriq overactive bladder $1,328 17% Vesicare overactive bladder $857 -7% Mycamine Candidiasis $311 -16% Micardis hypertension $204 -18%
Astellas reported flat revenues of $11.7 billion for 2018. It's prostate cancer drug Xtandi was again its top seller with $3 billion in sales, up 13%, while development is ongoing to expand the indication to earlier stages of prostate cancer.
The year kicked off for Astellas closing its $450 million purchase of Mitobridge at the end of January 2018. At the time, the two companies had an existing R&D collaboration in place focused on developing drugs that target mitochondrial function. These drug candidates have the potential to treat genetic, metabolic or neurodegenerative disorders as well as conditions of aging. MA-0211, the most advanced program emerging from the collaboration, was in Phase 1 studies for Duchenne Muscular Dystrophy (DMD).
The year continued with the Japanese pharma major on the acquisition hunt and bolstering its cell and gene therapy capabilities. It acquired Universal Cells, gaining the proprietary Universal Donor Cell technology to create cell therapy products that do not require Human Leukocyte Antigen (HLA) matching, potentially overcoming a huge treatment challenge by reducing the risk of rejection.
Next, Astellas inked a deal for UK-based gene therapy company Quethera, which is focused on developing novel treatments for ocular disorders. Astellas gains Quethera's ophthalmic gene therapy program, which uses a recombinant adeno-associated viral vector system (rAAV) to introduce therapeutic genes into target retinal cells for the treatment of glaucoma.
At the end of the year, Astellas purchased Potenza Therapeutics following the successful outcome of a collaboration agreement to build a portfolio of novel immuno-oncology (IO) therapies. The clinical IO therapies developed may also provide a platform for IO combinations with Astellas' existing non-IO programs for life cycle management and future novel IO combinations. Together the companies discovered and developed three investigational new drugs (INDs) with the potential to treat various cancers that are non-responsive or resistant to the current generation of IO therapies. These programs target immune stimulation, immune checkpoint inhibition, and regulatory T cell function and include: ASP8374/ PTZ-201, an anti-TlGIT antibody and ASP1948/PTZ-329, an antiNRP1 antibody, both of which are currently in Phase I studies; and ASP1951/PTZ-522, a novel format GITR agonistic antibody, which has achieved IND clearance.
During the year, Astellas expanded its cell and gene therapy infrastructure on three fronts, beginning construction of new research, development and manufacturing facilities, in Japan and the U.S. The Center for Active Ingredient for Biopharmaceuticals will be built at the Toyama Technology Center of Astellas Pharma Tech, a production subsidiary of Astellas. It will be capable of manufacturing antibodies for use in both clinical trial materials and commercial products, while also manufacturing products that include other modalities such as cell therapy. The new Center for Multimodality CTM, at the Tsukuba Biotechnology Research Center of Astellas in Japan, will be responsibile for the manufacture of CTM for use in early-stage clinical trials designed for the purpose of developing cell therapies and gene therapies for patients in Japan, U.S. and Europe. Lastly, the Astellas Institute for Regenerative Medicine, a center of the R&D of regenerative medicine and cell therapy located in Massachusetts, will move to a new location within the state and will be upgraded.
Headquarters: Tokyo, Japan
HEADCOUNT: 31,800 YEAR ESTABLISHED: 1921 REVENUES: $11,710 (+4%) NET INCOME: $982 (+4%) R&D: $1,959 (+4%)
DRUGS APPROVED DRUG INDICATION REXULTI schizophrenia Samsca/JINARC/ JYNARQUE Autosomal Dominant Polycystic Kidney Disease DRUGS FILED DRUG INDICATION LONSURF gastric cancer PHASE III DRUG INDICATION brexpiprazole major depressive disorder, adjunctive therapy, agitation associated with Alzheimer-type dementia TAS-116 gastrointestinal stromal tumor ASTX727 myelodysplastic syndrome fremanezumab migraine TAS-118 gastric cancer SGI-110 acute myeloid leukemia ASTX727 Myelodysplastic syndromes tolvaptan Syndrome of inappropriate antidiuretic hormone secretion vadadustat renal anemia delamanid Multidrug-resistant tuberculosis QPF-105 Peripheral parenteral nutrition EARLY RESEARCH PROJECTS DRUG INDICATION TAS0313 solid cancer TAS0728 solid cancer ASTX029 solid cancer TBI-1301 synovial sarcoma TBI-1501 acute lymphoblastic leukemia OPC-167832 tuberculosis
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Ability Maintena, schizophrenia, $2,307 36% Rexulti, Samsca hyponatremia Jinarc
Revenue in Otsuka's pharmaceutical segment was up 4% for the year at $11.7 billion. In the company's main area of psychiatry and neurology, sales of antipsychotic agent Ability Maintena grew 36% to $2.3 billion. Also, the new antipsychotic agent Rexulti was launched in April 2018 for schizophrenia.
Otsuka's research areas are in psychiatric and neurological diseases, hematological cancers, and kidney, cardiovascular, and infectious diseases. The company is placing an emphasis on discovery and development platforms for antibody development as a means to increase the efficiency of drug discovery across its programs and in addition to conventional R&D processes.
Towards efforts to diversify its portfolio, Otsuka acquired clinical stage biotech Visterra for approximately $430 million. The company's Hierotope platform, comprised of novel computational and experimental technologies, enables the design and engineering of precision antibody-based therapies that specifically bind to, and modulate, disease targets that are not adequately addressed by current technologies in antibody therapeutics. Visterra's pipeline includes programs targeting IgA nephropathy and other kidney diseases, cancer, chronic pain and infectious diseases.
During the year Otsuka reinforced its commitment to provide new advancements in digital medicine products and care models to address the needs of patients suffering from severe mental illness. With Proteus Digital Health, based in CA, it signed an expanded global collaboration for the further development and commercialization of a portfolio of medicines including the Ability Mycite (aripiprazole tablets with sensor) offering, which received NDA approval from the FDA in November 2017.
In another deal Otsuka America and Click Therapeutics signed a collaboration agreement for Otsuka and Click to develop and commercialize a prescription digital therapeutic for treatment of Major Depressive Disorder (MDD).This collaboration will leverage Click's ability to discover and validate a software application and deploy it commercially, with Otsuka's expertise in developing approved prescription therapies for patients with serious mental illnesses.
Otsuka says digital therapeutics align naturally with psychiatry and have significant potential to transform mental healthcare. Together, with its partners, Otsuka aims to bring to market a new offering that will provide a novel treatment for patients with MDD.
On the cancer research front, Osaka University and Otsuka Pharmaceutical entered into a licensing agreement for novel CAR-T cell therapy for multiple myeloma. It also teamed up with Takara Bio for co-development and sales rights in Japan to NYESO-1 siTCR and CD19 CAR gene therapies.
Expanding its global reach, Otsuka announced during the year the establishment of a new foreign subsidiary, Otsuka Pharmaceutical (Singapore), which held an opening ceremony on in May 2018.
Headquarters: Canonsburg, PA
HEADCOUNT 35,000 YEAR ESTABLISHED 1970 REVENUES: $11,434 (-4%) NET INCOME: $353 (-49%) R&D: $705 (-10%)
DRUGS APPROVED DRUG INDICATION Yupelri COAD/COPD Symfi Lo HIV Cimduo HIV treatment Symfi Lo HIV treatment Vancomycin HCL Staphylococcal infections DRUGS FILED DRUG INDICATION Dolutegravir, Emtricitabine & TenofowAlafenamide HIV BPaL Tuberculosis (TB) DRUGS IN PHASE III DRUG INDICATION Aspart Diabetes, type I (juvenile onset) M710 Macular oedema TPM/Daptomycin Skin infections, Bacteraemia
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Glatiramer Acetate Multiple Sclerosis $541 372% EpiPen Anaphylaxis, General allergy indications $218 -49% Esomeprazole Magnesium GERD, Ulcers $202 -3% Fentanyl Pain $193 -6% Zonalon Pruritus $173 13%
It was a challenging year for Mylan, plagued with valsartan recalls, remediation efforts, and ongoing drug shortages for EpiPen. Financially, the first quarter revealed the company's tribulations are far from over, with revenues down 7% to $2.5 billion and a loss of $25 million, as compared to earnings of $87.1 million in 1Q18. North America sales were down 6% and sales in Europe were down 14% primarily driven by a competitive environment and the impact of the $58.8 million Morgantown plant remediation activities, partially offset by new product sales, including Wixela Inhuband Fulphila (biosimilar to Neulasta), and increased market share on Glatiramer Acetate Injection.
On November 20, Mylan initiated a voluntarily recall of certain valsartan-containing products due to detected trace amounts of an impurity, N-nitrosodiethylamine (NDEA), (classified as a probable human carcinogen) contained in the API Valsartan, manufactured by Mylan Laboratories. Valsartan is used for the treatment of high blood pressure, heart failure, and to reduce cardiovascular mortality following a heart attack.
In December, the recall was expanded to include another 104 lots, including Amlodipine and Valsartan Tablets, Valsartan Tablets and Valsartan and Hydrochlorothiazide Tablets.
Additionally, Mylan's manufacturing license for valsartan was suspended by European authorities after NDEA was found in some batches of the hypertension drug made at the company's facility in Hyderabad, India.
Also in November, the company received a warning letter from the FDA relating to its manufacturing facility in Morgantown, West Virginia, citing problems with cleaning and quality control systems. As part of the ongoing restructuring and remediation activities, Mylan discontinued a number of products from the site while transferring some products to other sites. That being said, Mylan does not expect to have any significant new product launches from the site in 2019.
To top that off, May 10th 2019 marked one year of the EpiPen shortage, which is expected to drag on. According to a statement last August, Mylan's manufacturing partner Meridian Medical Technologies, a Pfizer company, continued to experience interruptions in the production of EpiPen (epinephrine injection, USP) and EpiPen Jr. At that time, over the past few months, there was intermittent supply as the company explored several options with Pfizer to help stabilize supply. Sterile injectables require a highly complex and technical manufacturing and assembly process and despite the company's best efforts, further supply shortages were anticipated. In June, Pfizer and Mylan announced that they are working with the FDA to extend the expiration dates by four months on all lots of EpiPen, with the exception of EpiPen Jr., in an effort to help alleviate shortages.
In more recent bad news, in May, 44 states filed a lawsuit alleging pharmaceutical companies colluded to fix the prices on their generic drugs, in which Mylan is a defendant. According to a UBS estimate, Mylan faces litigation charges of $1.1 billion.
On the bright side, Mylan and Fujifilm Kyowa Kirin Biologics Co. were granted marketing authorization from the EU for Hulio, a biosimilar to AbbVie's Humira, for all indications. Mylan plans to launch Hulio across various markets in Europe on or after October 16. Humira is the world's top-selling drug with nearly $20 billion in sales in 2018.
Headquarters: Tokyo, Japan
HEADCOUNT: 14,887 YEAR ESTABLISHED: 2005 REVENUES: $8,659 (flat) NET INCOME: $688 (-14%) R&D: $2,129 (+10%)
DRUGS APPROVED DRUG INDICATION Vanflyta relapsed, refractory acute myeloid leukemia DRUGS FILED DRUG INDICATION Pexidartinib bone cancer Quizartinib acute myeloid leukemia PHASE III DRUG INDICATION DS-8201 breast cancer Tesetaxel breast cancer VN-0105 Haemophilus influenzae type b (Hib) prophylaxis Heartcel Congestive heart failure Pentavac Diphtheria prophylaxisr
DRUGS COMING OFF PATENT DRUG INDICATION YEAR Nexium GERD 2019 Relenza Influenza 2019
TOP SELLING DRUGS DRUG INDICATION 2018 SALES (+/-%) Lixiana deep vein thrombosis $1,061 53% Nexium GERD $706 -10% Benicar Hypertension $486 -45% Namenda Alzheimer's disease $453 3% Injectafer Anaemia, iron-deficiency $399 29% Loxonin Musculoskeletal inflammation $275 -16% Venofer Anaemia in chronic kidney disease $261 -7% Prolia Osteoporosis $247 18% Inavir Influenza $164 -28%
It was busy and transformative year for Daiichi-Sankyo, as it returns to the top 25, and 2019 is shaping up to be another year of change for the company. Daiichi recently made organizational changes to oversee strategic priorities that aim to deliver seven new molecular entities in oncology by 2025. Sunao Manabe took the helm as CEO on June 17th succeeding George Nakayama, who will continue to serve as chairman.
As part of its efforts to establish a more efficient production system and become a global pharma innovator with a competitive advantage in oncology, Daiichi transferred and sold domestic manufacturing and assets for 41 long-listed products, from antacids to antibiotics, to Alfresa Pharma Corp. for $78 million. Daiichi has been focusing on oncology, targeting 500 billion yen ($4.5 billion) in annual sales from the business in fiscal 2025 from 20 billion yen in 2017.
In June, Ministry of Health, Labor and Welfare (MHLW) of Japan approved VANFLYTA (quizartinib) for the treatment of relapsed/refractory FLT3-ITD acute myeloid leukemia (AML), as detected by an MHLW-approved test. Quizartinib is aimed at treating AML patients with a specific genetic mutation called FLT3.
However, in May, independent experts on an advisory panel to the U.S. FDA voted 8-3 against the treatment after assessing data presented by the company. The FDA is not bound by these recommendations and the NDA for quizartinib is currently under FDA Priority Review. A decision is expected by August 25, 2019. On June 24, Daiichi received a Complete Response Letter from the FDA and will determine the next steps in the U.S.
Separately, an advisory committee voted 12-3 in favor of the approval of pexidartinib, another treatment from Daiichi, that aims to treat a type of rare, non-cancerous tumor usually affecting joints and limbs. If approved by the FDA, pexidartinib would be the first and only therapy for tenosynovial giant cell tumor, which is associated with severe morbidity or functional limitations, and not amenable to improvement with surgery. Pexidartinib is among the seven new molecular entities that Daiichi is committed to delivering from its oncology pipeline by 2025.
A clinical trial collaboration with Merck KGaA and Pfizer is evaluating the combination of trastuzumab deruxtecan (DS8201), an HER2 targeting antibody drug conjugate (ADC), in combination with the checkpoint inhibitor avelumab and/or an investigational Merck KGaA, DNA damage response (DDR) inhibitor, in patients with HER2 expressing or mutated solid tumors. A separate research collaboration is evaluating trastuzumab deruxtecan in combination with avelumab, the DDR inhibitor and other investigational compounds in Merck KGaA's and Pfizer's pipelines.
Additionally, a global development and commercialization agreement with AstraZeneca is exploring trastuzumab deruxtecan for multiple HER2 expressing cancers including breast and gastric cancer, as well as non-small cell lung and colorectal cancer. The companies will jointly develop and commercialize trastuzumab deruxtecan as a monotherapy or a combination therapy. Daiichi Sankyo will be responsible for manufacturing and the supply of trastuzumab deruxtecan.
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|Date:||Jul 1, 2019|
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