Voxelotor

With the multinational pharma corporation (MNCs) annual reporting season for 2023 recently completed, GBI reviews company reports for performance highlights and trends, both globally and in the China market.The last 12 months saw the collapse of a mountain of COVID-19 vaccine sales, meaning that Pfizer lost its position as the leading pharma revenue generator globally to Johnson & Johnson. The lack of COVID competition allowed Merck, Sharp & Dohme’s PD-1 inhibitor Keytruda (pembrolizumab) to emerge as the world’s top-selling drug. However, the fact that more than half of the leading top - 20 blockbusters are either already off-patent or facing loss of exclusivity by 2028 underlines the urgency behind the recent surge in deal-making by Big Pharma. Meanwhile, in China, the success of one crucial product has seen Merck, Sharp & Dohme eclipse AstraZeneca as the market’s leading MNC pharma. J&JDisplaces Pfizer at Top of Revenue LeaderboardAfter underwhelming returns from its COVID-19 vaccine, the US giant Johnson & Johnson (J&J) returned to form in 2023. Focusing solely on pharmaceutical sales (as per all sales figures in this report), J&J generated USD 54.76 billion after growth of 4.8% year-on-year (YOY). J&J products occupied 4 of the top-20 selling drugs globally if co-development partnerships are included. The portfolio is led by auto-immune disease drug Stelara (ustekinumab), which hit USD 10.85 billion in 2023 sales, up 9% YOY, but faces its first biosimilar competitors in 2024, the first approved in Europe in January this year. Anti - CD38 antibody Darzalex (daratumumab), used to treat multiple myeloma (MM), hit USD 9.74 billion, up 22.2% YOY, and retains market exclusivity until 2029.Of the firm’s new launches, chimeric antigen receptor (CAR) T cell therapy Carvykti (ciltacabtagene autoleucel), in-licensed from China’s Legend Biotech, was a strong performer, with sales reaching USD 500 million during the year, up from USD 133 million in 2022. CEO Joaquin Duato underlined that “with more than 2,000 patients treated with Carvykti, it's already the fastest launched CAR-T in the market overall”. J&J is seeking approval for Carvykti as a second-line or later MM therapy, with a PDUFA date of April 4, 2024, and has taken steps to expand its lentivirus manufacturing capabilities in the US, as well as sites in the Netherlands and Switzerland, to meet expected growing demand for the therapy. An FDA investigation into the safety of CAR-Ts in general was also shrugged off by J&J, Duato noting: “We remain confident in ... both the risk-benefit of Carvykti in the indication that is being studied and at the same time on the potential of Carvykti to be a USD 5 billion plus asset at peak year sales”. Low-Key Deal-MakingAlthough J&J made no blockbuster multi-billion-dollar acquisitions during 2023, the firm has worked quietly to strongly expand its pipeline.“ CFO Wolk underlined the firm’s deal making during the year, when USD 3 billion was deployed for licensing and acquisitions. ”That included the purchases of antibody drug conjugate (ADC) specialist Ambrx for USD 2 billion and atrial fibrillation medtech firm Laminar for USD 400 million “as well as more than 50 smaller early stage licensing deals and partnerships that complement our current  Innovative Medicine and MedTech pipelines”. The firm expects another strong year of 5%-6% growth in 2024.PfizerRecord Year of Approvals Bodes Well for FutureHaving led the world for the last two years in revenue terms, Pfizer’s fall from its COVID pinnacle of USD 99 billion biopharmaceutical sales in 2022 was faster than had been predicted after sales targets were missed due to cancelled government contracts for COVID-19 therapy Paxlovid (nirmatrelvir/ritonavir) and vaccine Comirnaty. Revenues from pharma sales were down -45% YOY, however, excluding COVID-19 products, global sales were up a respectable 7% YOY.Pfizer had 3 products in the global top-20 rankings, including the anticoagulant Eliquis (apixaban), the Prevnar family of vaccines, and the Comirnaty COVID vaccine. However, both Eliquis and Prevnar face patent expiration in 2026, while Comirnaty is unlikely to feature heavily in 2024. Nevertheless, Pfizer’s in-house pipeline and recent acquisitions are expected to produce a soft landing. There were a record nine US FDA new drug approvals during 2023, for: migraine therapy Zavzpret (zavegepant), RSV vaccine Abrysvo, alopecia treatment Litfulo (ritlecitinib), growth hormone Ngenla (somatrogon), multiple myeloma drug Elrexfio (elranatamab), ulcerative colitis drug Velsipity (etrasimod), Neisseria meningitidis vaccine Penbraya, as well as Comirnaty and Paxlovid. Abrysvo and the 2022-acquired migraine therapy Nurtec ODT/Vydura (rimegepant) as well as sickle cell disease treatment Oxbryta (voxelotor) were among the recent launches to begin making meaningful commercial contributions. Seagen AcquisitionMuch of Pfizer’s COVID windfalls went towards the USD 43 billion acquisition of antibody drug conjugate (ADC) pioneer Seagen, a deal which closed in December 2023. Pfizer CEO Albert Bourla, speaking during the earnings conference call, underlined the importance of the acquisition to the company’s future, described as putting Pfizer “in a strong position... to achieve a world-class oncology leadership”. Pfizer’s oncology-focused R&D resources were immediately doubled thanks to the merger, as well as commercial network gains. The deal doubles Pfizer’s oncology pipeline and is expected to produce an immediate USD 3.1 billion positive impact on 2024 revenues, helping Pfizer to raise its 2024 financial guidance into a range between USD 58.5 billion and USD 61.5 billion total revenues.Seagen’s current lead product is Padcev (enfortumab vedotin), a treatment for bladder cancer being co-developed with Astellas. First approved in 2019, Pfizer/Astellas secured a significant new indication approval for the drug in December 2023, the US FDA giving the nod for Padcev’s use alongside Keytruda (pembrolizumab) in first-line urothelial carcinoma. Wall Street sales forecasts for Padcev average at around USD 2.8 billion by 2030.One of the motivations behind Pfizer’s recent cost-cutting drive has been to free up resources to support the commercial launch of so many new products. New molecular entities (NMEs) are forecast to potentially generate up to USD 20 billion in new revenues  by 2030, when a further USD 25 billion is forecast to be derived from the US giant’s licensing and acquisition deal-making. MSDKeytruda Claims its Rightful PlaceFor Merck, Sharp & Dohme (MSD), the programmed death-1 (PD-1) inhibitor Keytruda (pembrolizumab) took its place at the top of the global drug sales charts for the first time in 2023. The molecule generated USD 25 billion of MSD’s total USD 60.1 billion in revenues during 2023 after 21% YOY growth. Human papillomavirus (HPV) vaccine family Gardasil/Gardail-9 also enjoyed  a strong year with 29% YOY expansion to be just outside the  top-10 best-selling drugs globally in 2023 with USD 8.9 billion in sales.That means that Keytruda and Gardasil sales combined accounted for over 63% of MSD’s total pharma sales. First approved by the US FDA in 2014, Keytruda’s core patent in the US runs out in 2028. Gardasil was first approved in 2006 and is already off-patent, while Gardasil-9 was first approved in 2017 and is also set to lose exclusivity in 2028.However, Gardasil already faces competition in China – among the vaccine’s most significant markets globally – from locally developed innovative HPV vaccines, including 9-valent products.Like many of MSD’s peer companies, stocking the pipeline with the next generation of products to replace Keytruda and Gardasil is clearly a priority. Of note, 14 of the top-20 drugs by global sales are either already patent-expired or face loss of exclusivity within the next 4 years or less. MSD’s response was to put around USD 30 billion into R&D investments during 2023. That included the USD 10.8 billion acquisition of US biotech Prometheus Biosciences which closed in June 2023, mainly targeting PRA023, a tumor necrosis factor (TNF)-like ligand 1A (TL1A)-targeted antibody in late-stage development for autoimmune diseases including ulcerative colitis and Crohn’s  disease. And in October, Merck paid USD 4 billion upfront as part of a potential USD 22 billion partnership with Daiichi Sankyo, taking ex-Japan development rights to three antibody drug conjugates (ADCs). That deepened MSD’s involvement in the ADC space, following three significant deals with China’s Sichuan Kelun Pharmaceutical signed in 2022, cumulatively worth north of USD 10 billion in total commitments. MSD’s BD activity over the last three years means it has built a formidable pipeline covering three core therapeutic areas of oncology, cardiometabolic diseases, and immunology, with a potential USD 15 billion in forecast potential sales for the pipeline added by deal-making during 2023. Over 20 Phase III trials were initiated during 2023, and an even greater number is expected for 2024. Potential market is untapped70% of Gardasil’s potential market in China still untapped: Finally, MSD’s China performance is worthy of note. The region produced sales growth of 20% during Q4 to USD 1.5 billion, and rose 32% YOY over the 12 months to USD 6.71 billion in sales – over 12% of MSD’s global pharma total – meaning that MSD cemented its place as currently the leading pharma company in China.Gardasil remains the key driver, and during the earnings conference call investors questioned whether the locally approved innovative HPV vaccines pose a threat to future growth, particularly considering that one domestic firm recently received approval for a two-dose regimen.CEO Rob Davis voiced his confidence in MSD’s ability to maintain “a vast majority of share in the private market”. The US firm continues to mainly target urban females in Tier 1 to Tier 3 cities, a population of about 200 million, of which, Davis noted, “probably about 30% have actually received vaccination. So, you are still looking at 120 million, 130 million eligible population”. With most of the local competitors targeting lower-tier cities and a different population, MSD remains bullish on its prospects in China. MSD also submitted data for Gardasil in male subjects late last year, and could gain approval later this year for that new market segment.

NEW YORK, Feb. 05, 2024 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering treatments for genetically defined cardiovascular diseases and APOE4-associated Alzheimer's disease, today announced new executive appointments to lead the evolution of the company’s pipeline into late-stage clinical development. “The accumulating talent bench at Lexeo has overseen some of the most transformative clinical development programs, drug approvals and product launches in rare disease and precision cardiovascular medicine,” said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics. “We look forward to benefiting from this group’s thought leadership and operational experience as we progress the Lexeo pipeline towards late-stage studies.” The appointments include: Sandi See Tai, MD, has been promoted to Chief Development Officer. Prior to Lexeo, Dr. See Tai was VP & Development Head for Rare Disease at Pfizer, responsible for setting the Rare Disease internal portfolio strategy and delivering its clinical development portfolio of investigational products and in-line assets. She served as the Medicine Team Lead for clinical programs across multiple therapeutic areas including Rare Cardiovascular, Neurology, Renal and Pulmonary disease areas. During her tenure, Dr. See Tai led the late-stage clinical development program of tafamidis for ATTR cardiomyopathy (ATTR-ACT), which achieved global regulatory approvals, and the Phase 3 LMNA dilated cardiomyopathy clinical program. In addition to late-stage clinical development, Dr. See Tai was responsible for strategic clinical planning for early-stage development candidates such as those for other genetic cardiomyopathies and Duchenne Muscular Dystrophy. With almost 20 years of experience in the pharmaceutical industry, Dr. See Tai held multiple roles of increased scope and responsibility across Global Medical Affairs in Transplantation at Wyeth Pharmaceuticals before moving into clinical development at Pfizer. Prior to joining the pharmaceutical industry, Dr. See Tai was Assistant Professor of Pediatrics at Drexel University College of Medicine and Attending Physician in Pediatric Nephrology at St. Christopher’s Hospital for Children, Philadelphia, where she also completed her General Pediatrics residency and Pediatric Nephrology fellowship. She received her MD from Tufts University School of Medicine, Boston.Eric Adler, MD, has been appointed Chief Medical Officer & Head of Research. As a pioneer and thought leader in cardiovascular gene therapy, Dr. Adler formerly served as Chief Scientific Officer at Lexeo since joining in 2022. Prior to this role, Dr. Adler served as Professor of Medicine, head of the Heart Failure Section, Director of the Strauss Center for Cardiomyopathy, and the Czarina and Humberto S. Lopez Chancellor’s Endowed Chair in Cardiology at the University of California, San Diego (UCSD). Dr. Adler’s work has led to the development of a novel cardiovascular gene therapy candidate entering late-stage clinical development. His research is focused on the study and treatment of cardiomyopathy, and he has published over 100 papers in peer reviewed journals on the topic. Dr. Adler is currently an associate editor of Circulation Hearth Failure and has served on leadership, grant review, and guidelines committees for the American Heart Association, the Heart Failure Society of America, the International Society of Heart and Lung Transplant, and the National Institute of Health. Dr. Adler earned his medical degree from the Boston University School of Medicine.Rajiv Patni, MD, has been appointed Senior Advisor to the Chief Executive Officer and Board of Directors of Lexeo. Dr. Patni was formerly Chief Research and Development Officer at Reata Pharmaceuticals (acquired by Biogen for $7.3 billion), a commercial-stage biopharmaceutical company that received approval for Skyclarys, the first FDA-approved therapy for Friedreich’s ataxia. Prior to this role, Dr. Patni served as Chief Medical Officer at several public, small-cap, commercial-stage biopharmaceutical companies including Portola (acquired by Alexion for $1.4 billion) and Global Blood Therapeutics (acquired by Pfizer for $5.4 billion) and at those companies, Dr. Patni oversaw the clinical studies leading to the approvals of Andexxa and Oxbryta. Dr. Patni joined these companies at inflection points in their research and development growth trajectories and significantly supported their successful acquisitions. Over his 24-year industry tenure in global product development, Dr. Patni has contributed to the development of 21 new chemical entities in several therapeutic areas including cardiology, diabetology, hepatology, neurology, and benign hematology. His experience in fostering successful teams from 35 to 250 colleagues contributed to the approval of 11 medicines from the US FDA, EMA, and other regulatory agencies. The recent approvals include medicines for several rare diseases such as pulmonary arterial hypertension, advanced Parkinson’s disease, sickle cell disease, and Friedrich’s ataxia. Dr. Patni received his MD from the Mount Sinai School of Medicine in New York City as part of an accelerated BS/MD Program. He completed his internal medicine residency and adult cardiology fellowship at the Albert Einstein College of Medicine, also in New York City, where he continued as an attending physician-scientist before joining the biopharmaceutical industry. Jenny R. Robertson has been appointed Chief Business and Legal Officer. Ms. Robertson formerly served as Chief Legal and Administrative Officer at Lexeo, leading legal, human resources, information technology, information security, and facilities strategies and activities. Prior to Lexeo, Ms. Robertson served as Chief Counsel to Pfizer’s Oncology Business Unit and held other senior legal roles including Chief Counsel for Pfizer’s Rare Disease Business Unit, where she led the global legal team for five years. Across positions at Pfizer, Ms. Robertson counseled clients on a range of business and legal matters including commercialization, disclosure, business development, alliance management, clinical development, intellectual property issues and litigation. Before joining Pfizer in 2010, Ms. Robertson spent 10 years in private practice with a large international law firm in New York and Washington, D.C., engaged in complex commercial litigation with a healthcare focus. Ms. Robertson holds a Bachelor of Arts Degree in Political Science from Southern Illinois University and a J.D. from the Georgetown University Law Center, where she co-founded and served as Editor-in-Chief of The Georgetown Journal of Gender and the Law. About Lexeo TherapeuticsLexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to transforming healthcare by applying pioneering science to fundamentally change how genetically defined cardiovascular diseases and APOE4-associated Alzheimer’s disease are treated. Using a stepwise development approach, Lexeo is leveraging early proof-of-concept functional and biomarker data to advance a pipeline of cardiovascular and APOE4-associated Alzheimer’s disease programs. Media Response:Janine Bogris(201) 245-6838janine.bogris@canalecomm.com Investor Response:Laurence Watts(619) 916-7620laurence@gilmartinir.com