Obeticholic acid

For many people, the end of the year is a mad rush to wrap things up before the holidays, and so it was for the FDA. Notable regulatory decisions include the first drug approval for a prevalent chronic condition and a novel regenerative medicine approach to help trauma patients. In one case, a new drug approval comes as its developer takes on a new identity in the new year. Here’s a look back at some highlights from a busy regulatory month: presented by Health IT Transforming Patient Care: The Role of AI-Powered Assistants The progress in artificial intelligence (AI) is reshaping patient care, across various dimensions, from facilitating faster discharge to curating treatment plans and suggesting lifestyle changes. By IT Medical Notable Firsts —The prevalent sleeping disorder obstructive sleep apnea has historically been managed with a medical device that helps breathing. Eli Lilly’s Zepbound is now the first FDA-approved drug treatment for the chronic condition. Obesity is a risk factor for sleep apnea and clinical trial results showed that weight reductions from treatment with Zepbound were accompanied by breathing improvement. Approval in obstructive sleep apnea adds another potential blockbuster indication for a metabolic medication that has fast become one of Lilly’s top-selling products. —Patients who have the rare inherited metabolic disorder familial chylomicronemia syndrome lack the ability to break down triglycerides, a type of fat from food. The only way to avoid potentially fatal complications to the pancreas is by maintaining an extremely restrictive diet. Approval of Ionis Pharmaceuticals’ olezarsen gives patients a therapeutic option. The once-monthly injected genetic medicine, which is designed to block the body’s production of a liver protein that regulates triglyceride metabolism, will be marketed under the brand name Tryngolza. Ionis previously brought drugs through late-stage development and commercialization under partnerships with larger companies. Tryngolza will be the first product Ionis commercializes on its own. —When trauma to an arm or leg requires replacement of a blood vessel, the standard treatment is grafting a vein from the patient or implanting a synthetic vein. Now there’s a new regenerative medicine option. Humacyte won FDA approval for Symvess, a bioengineered blood vessel for restoring blood flow to avoid the loss of a limb when grafting a vein from the patient is not feasible. Here’s more about the biotech’s regenerative technology. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech —Mesoblast’s regulatory approval was a long time coming. In 2020 and 2023, the FDA turned down the Australian company’s application for remestemcel, an allogeneic cell therapy for graft versus host disease, an immune response that develops when donor T cells attack the recipient’s cells following a transplant procedure. Remestemcel, brand name Ryoncil, is a made from mesenchymal stromal cells sourced from the bone marrow of healthy donors. The product’s approval covers acute graft versus host disease that is refractory to treatment with steroids in patients age 2 months and older. It’s the first affirmative regulatory decision for a cell therapy made from mesenchymal stromal cells. Approvals in Immunology —Vtama, an Organon drug acquired from Roivant Sciences earlier this year, received FDA approval as a treatment for atopic dermatitis in adults and children age 2 and older. The drug is topical cream that was initially approved in 2022 as a treatment for plaque psoriasis. Approval in atopic dermatitis brings the product to a much larger dermatologic indication, albeit one served my many branded and generic medications. —In other atopic dermatitis news, Galderma landed FDA approval for nemolizumab, brand name Nemluvio. The drug is an antibody designed to block IL-31, a signaling protein associated with the itch and inflammation of the chronic skin disorder. FDA approval of Nemluvio covers use of the drug in patients age 12 and older who have moderate-to-severe atopic dermatitis. It’s the second approval in the past year for Nemluvio, which was first approved over the summer as a treatment for prurigo nodularis. Rare Disease Regulatory Decisions —Neurocrine Biosciences received approval for Crenessity, a treatment for the rare inherited hormone disorder congenital adrenal hyperplasia. The small molecule helps bring the hormone imbalance back to more normal levels. The FDA approved a pill formulation for adults and an oral solution for pediatric patients. Analysts project Crenessity could achieve blockbuster sales, pending regulatory approvals in other countries. —Novo Nordisk is best known for metabolic medicines, but its rare disease portfolio is getting a boost with FDA approval of Alhemo, a drug that reduces bleeding episodes in patients with either hemophilia A or B. Alhemo, known in development as concizumab, is an antibody designed to bind to TFPI, preventing that protein from blocking factor Xa, a different protein that plays a role in blood clotting. That’s the same mechanism of action as Pfizer’s Hympavzi, which won its FDA approval in October. Both drugs are subcutaneous injections that provide alternatives to intravenously infused hemophilia therapies. But Pfizer’s once-weekly Hmypavzi has a dosing edge over Alhemo, which must be injected once daily. —Vertex Pharmaceuticals is adding a new cystic fibrosis (CF) drug to its portfolio with FDA approval of Alyftrek, which combines three compounds in a single therapy. Like Vertex’s other CF therapies, Alyftrek is a modulator of the CFTR a protein that regulates the movement of chloride ions into and out of cells. Alyftrek’s approval is based on clinical data comparing the once-daily therapy to Trikafta, a Vertex triple combination drug initially approved in 2019 as a twice-daily CF treatment. Results showed Alyftrek was non-inferior to Trikafta on a key measure of lung function and was superior in reducing sweat chloride levels, which is a surrogate indicator of the function of CFTR proteins. Besides the dosing advantage, Alyftrek addresses 31 additional mutations that are not addressable by other CFTR modulators. The Dec. 20 approval of Alyftrek came nearly two weeks ahead of the Jan. 2 target date for a regulatory decision. Developments in Cancer Drugs —The FDA awarded accelerated approval to Merus Therapeutics drug zenacutuzumab as a treatment for advanced cases of two types of cancer: non-small cell lung cancer and pancreatic adenocarcinoma. It’s the first approval for a drug that addresses a genetic signature called an NRG1 gene fusion. Netherlands-based Merus will market the bispecific antibody under the brand name Bizengri. In a deal struck days prior to the approval announcement, Partner Therapeutics licensed U.S. commercialization rights to Bizengri. —The blockbuster AstraZeneca drug Imfinzi expanded its FDA-approved uses to include limited-stage small cell lung cancer that has not progressed following concurrent platinum-based chemotherapy and radiation therapy. The checkpoint inhibitor was first approved in 2017 for bladder cancer and added extensive-stage lung cancer as a new indication in 2020. The drug’s latest approval is based on Phase 3 results showing a 27% reduction in the risk of death compared to a placebo. AstraZeneca said the FDA decision makes Imfinzi the first immunotherapy approved for limited-stage small cell lung cancer. —Xcovery Holdings drug ensartinib, brand name Ensacove, was approved to treat adults with advanced cases of non-small cell lung cancer that is positive for ALK mutations. Patients prescribed the once-daily pill must not have previously received an ALK inhibitor. —Pfizer cancer drug Braftovi landed accelerated approval as a first-line treatment for metastatic colorectal cancer driven by the BRAF V600E mutation. The approval covers use of the drug in combination with Eli Lilly’s Erbitux and the chemotherapy regimen referred to as FOLFOX, both standard colorectal cancer therapies. Braftovi, a small molecule inhibitor of BRAF V600E, was initially approved in 2018 for advanced cases of melanoma. The drug came from Pfizer’s 2019 acquisition of Array Biopharma. —Tevimbra, a cancer immunotherapy developed by BeiGene, received FDA approval as a first-line treatment for gastric and gastroesophageal junction cancers when used in combination with chemotherapy. It’s the second FDA approval for the checkpoint inhibitor, which was approved last March for treating advanced or metastatic esophageal squamous cell carcinoma after prior treatment with chemotherapy. The new year means a new identity for BeiGene. The cancer drug developer is changing its name to BeOne Medicines. Starting Jan. 2, the company’s stock symbol on the Nasdaq will be “ONC.” Rejections, Warnings & More Bad News in Biotech —Astellas Pharma’s bid to bring patients less-frequent eye injections of its drug Izervay was rejected by the FDA. Izervay, approved for treating geographic atrophy in 2023, is administered monthly to slow progression of the vision-loss disorder. Astellas sought approval for every-other-month dosing based on two-year Phase 3 data. According to Astellas, no safety benefit/risk issues were cited but the FDA took issue with a statistical matter related to labelling language proposed by the company. The rejection will limit Izervay’s ability to compete against Apellis Pharmaceuticals’ geographic atrophy drug Syfovre, which is approved for both monthly and every-other-month dosing. —In other Astellas news, the label for menopause drug Veozah now sports a black box warning for the risk of serious liver injury. The warning follows a FDA safety communication issued in September after a postmarketing report of a patient who developed signs and symptoms of liver injury after taking the once-daily pill for about 40 days. Veozah won FDA approval in 2023 as the first in a new class of therapies for menopause. —Applied Therapeutics received a double dose of bad regulatory news. First the FDA rejected the biotech’s application for govorestat, a drug developed as a treatment for the rare metabolic disease galactosemia. According to Applied, the agency cited “deficiencies in the clinical application.” Days after the FDA complete response letter, the FDA sent Applied a warning letter. The trial and the drug are redacted in the public version of the letter, but in a regulatory filing, Applied acknowledged the FDA’s concerns are about the govorestat galactosemia trial. Applied said the warning letter identified issues with electronic data capture and a dosing error in the dose-escalation portion of the study — both of which the company believed it had already addressed with the agency. Applied said it would respond to the FDA warning letter. —Bad news keeps stacking up for Intercept Pharmaceuticals and its drug, Ocaliva, a treatment for the rare liver disease primary biliary cholangitis (PBC). On Dec. 12, the FDA issued a safety alert, warning of the risk of serious liver injury in patients without advanced liver cirrhosis. The alert came one month after the FDA turned down Intercept’s application seeking full approval for Ocaliva, which won its accelerated approval in PBC in 2016. The FDA’s rejection letter for the drug cited safety concerns. When Ocaliva first reached the market, it was the only FDA-approved second-line treatment for PBC. In the past year, drugs from Ipsen and Gilead Sciences have each won accelerated approvals as new second-line therapies for the rare disease. Two weeks after the FDA turned down full approval of Ocaliva, the European Commission revoked the conditional marketing authorization for the drug. Advanz Pharma holds rights to Ocaliva in Europe. The company said the commission decision is subject to an ongoing annulment procedure in the EU’s General Court and a ruling is expected in 2025. —The FDA turned down Zealand Pharma’s glepaglutide as a treatment for short bowel syndrome, a rare disorder that develops when the small intestine is damaged or shortened, making it difficult for the organ to absorb nutrients. The drug is a long-acting GLP-2 analog intended to enhance the intestine’s ability to absorb nutrients, reducing patients’ dependence on intravenous feeding. According to Zealand, the FDA said the application needed more evidence of efficacy and safety. The company said it would discuss the letter with the FDA and proceed with plans to seek European approval in 2025. —Lexicon Pharmaceuticals came up short in its bid to expand approval of its drug, sotagliflozin (brand name Zynquista), to include the treatment of adults with type 1 diabetes and chronic kidney disease. The FDA’s Dec. 20 rejection of the drug followed a negative FDA advisory committee vote in October. The FDA approved sotagliflozin last year as a treatment for heart failure; it’s marketed in this indication under the brand name Inpefa. —Johnson & Johnson received a complete response letter for its injectable version of Rybrevant, a drug that treats cancer driven by EGFR mutations. Intravenously infused Rybrevant was approved in 2021 as a treatment for non-small cell lung cancer. The injectable version is made with technology from Halozyme. J&J said the FDA letter flagged manufacturing issues and did not cite any concerns about the new formulation or its safety and efficacy.

选择带领一家以成熟产品为主的“小而美”家族跨国药企在中国市场“做加法”，周勤的底气在于阿尔法西格玛的“产品力”，在于深刻认同公司传承几十年“以人为本”的价值核心， 以及始终保持对创新的激情，家人般的关爱，联结世界各地每位同事共创未来。 在当下风云变幻的全球制药市场环境中，大型跨国药企于中国市场的布局调整纷至沓来，精简业务、收缩战线似乎已是常态，然而，却有一家来自意大利的家族跨国药企——阿尔法西格玛，正在谋划一场“中国式加法”。 其不仅决意对已在中国市场深耕多年的成熟产品“再开发”，而且还规划在未来将新产品逐步引入中国市场的同时，将 OTC、保健品、特医食品，乃至 API供应与生产等业务板块统统纳入其在中国市场的战略版图之中。 通过聚焦治疗领域，实现多元化阿尔法西格玛产品组合方案，给中国医生和患者提供更优的选择。这就是今年5月底才刚刚履新的阿尔法西格玛中国区总经理周勤，9月提交给阿尔法西格玛全球总部并获得认可的全新中国战略。 阿尔法西格玛中国区总经理周勤 未来之路绝非坦途。对于周勤来说，摆在眼前的现状是如何率领阿尔法西格玛中国公司200人的团队，在只有成熟产品的当下，打破过往思维惯性，行动一致共赢未来？当前，组织架构正处于快速变革阶段，人才团队也在紧锣密鼓地优建过程中，当下，无疑是最重要的那个启航时刻。 01 启新程，做加法 2023年9月26日，作为全球首个在该领域进入临床III期的品种，奥贝胆酸在NASH适应证闯关FDA宣告折戟3个月后，其研发公司Intercept终于迎来了命运的转折点——阿尔法西格玛以8亿美元总价将其收至麾下。这一举措向外界清晰地昭示了阿尔法西格玛未来的发展方向：阿尔法西格玛将成为“全球创新型GI（消化道疾病治疗领域）前沿公司”。 作为全球最具潜力的原发性胆汁性胆管炎（PBC）用药，奥贝胆酸在2022年全球销售额就已经接近3亿美元，将其收入麾下在产品管线上是迈向未来目标的一大步，为阿尔法西格玛在全球市场的布局增添了一枚关键的棋子。 事实上，阿尔法西格玛在追求创新做大做强道路上从未停止过。2015年，其两家前身Alfa Wassermann和Sigma-Tau合并之时，就设立了提升在专科药物领域国际影响力的目标。2021年10月，伴随阿尔法西格玛新任首席执行官Francesco Balestrieri走马上任，这一目标再次被具像化。到2024年底，随着一系列创新药的引入和原有业务板块的强势增长，阿尔法西格玛的全球营收将达到20亿欧元。 周勤告诉E药经理人，“真正的全球创新型GI前沿公司”有三层含义：一是“全球化”，意味着总部将大力拓展意大利以外的全球市场版图以及增长；二是“GI前沿公司”，即聚焦消化肝病领域作为核心增长；三是“敏捷的创新型公司”， 也就是公司核心治疗领域创新产品（FIC/BIC）成为公司增长的最大引擎，这也是公司在创新驱动下实现产品多元化与高价值化的卓越成果。 为在中国实现这一宏伟目标，周勤将带领中国团队不仅要快速驱动上市多年的五个成熟产品的第二增长曲线，夯实公司基本面，完善升级业务运营体系，还要高度关注行业前沿，同步全球引进上市新的创新产品来进一步扩大中国业务的全面增长。就像数百年前探险家马可波罗的东方之旅，阿尔法西格玛的中国战略也将是一场新的探索。 2024年5月，周勤履新阿尔法西格玛中国总经理职位，但对于周勤来说，已经相当于一次创业。来到阿尔法西格玛，全球总部交给周勤的第一个任务就是要在三个月内制定出与全球发展步伐一致的中国市场变革策略。而其所隐藏的对周勤的考验是，如何在三个月内向全球总部呈现一个清晰且可执行的中国战略，从而可以充分挖掘中国市场的潜力。“总部最终接受并高度认可了中国市场的短、中、长期发展战略。”周勤以极简之语总结了此次考验的结局，且向E药经理人透露，阿尔法西格玛全球总部针对中国确立的最终战略为“China for China，China for global”。 两则短句的背后，彰显了阿尔法西格玛对中国市场即将开展的长远规划与大规模投入的雄心：2025-2028年业绩增长主要来源于现有产品以及部分新产品的拓展，同时积极寻找BD机会以及加速全球FIC/BIC产品管线在中国注册；2028年开始，全球创新产品的上市将会大大助力中国市场增长；更长远来看，基于成本优势，中国市场也极有可能进入阿尔法西格玛在全球的API供应链，并成为其生产基地的重要组成部分。“未来公司在中国的投入不仅能够赋能中国市场，甚至可以反哺全球。”周勤表示。 02 携新品，谋增长 “产品力”是一家公司在市场竞争中保持优势的基石。 现有产品的卓越“产品力”，加之阿尔法西格玛传承数十载对患者高度负责的理念，成为周勤向全球总部提出于三年内推动业绩进一步跃升的坚实底气所在。 阿尔法西格玛在中国的五大核心产品已经深耕市场多年，在各自领域具有独特的优势且依然具有进一步拓展的市场潜力。例如周勤手中的王牌——利福昔明-α晶型，“转型与突破”贯穿其成长始终。作为一款口服不被肠道吸收的局部抗菌药物，利福昔明-α晶型通过高效抑制有害菌，促进有益菌生长、抗炎，调节肠道免疫，最初用于肠道感染（包括急性和慢性肠道感染、腹泻综合征、夏季腹泻、旅行者腹泻和小肠结肠炎等）和高氨血症（肝性脑病），之后阿尔法西格玛又为其在FDA/CDA申请并获批了肠易激综合征和预防胃肠道手术术前术后肠道感染的适应症。 在周勤还未赴任阿尔法西格玛之前，与学科专家的交流中就屡屡听闻对利福昔明-α的赞誉之声。这让她意识到，利福昔明-α将是阿尔法西格玛短期业绩增长的关键。而同样以“产品力”在学科专家中获得盛誉的产品，阿尔法西格玛的管线中不仅只有利福昔明-α一款。 除了坚持“产品力”赋能业绩增长，阿尔法西格玛发展至今，也一直传承着创始人‘以人为本’的理念。周勤告诉E药经理人，在阿尔法西格玛中国的五大核心产品中，用于治疗慢性肾衰竭血透患者的左卡尼汀注射剂，在2023年的第八批集采中，主动宣布最大诚意的降价，在一众产品中以低价优质的身份中标造福患者。 此外，在周勤工作规划中还有提升品牌的知晓度与药品可及性，她希望阿尔法西格玛中国未来将“两条腿走路”，让院外渠道也成为现有产品的拓展空间，提升药品对患者的可及性。 当然，在跨国药企中国区“创业”的周勤，并不回避向全球总部汇报中国市场所面临的挑战。2018年开启的国家组织药品集中采购与2019年开始每年更新的医保目录准入谈判，让“灵魂砍价”的故事常态化上演。但周勤却在环境带来的种种挑战中，发现了可以抓住的机遇：一是老龄化趋势下，市场规模庞大；二是集采与医保谈判虽然让多数药企感受到控费压力，但政府鼓励创新的意图显著。同时，在中国加入ICH后，药品审评审批与注册技术要求逐渐与国际接轨，进口创新药在中国的获批时间与全球基本可以做到同步。 “这恰恰与阿尔法西格玛全球的战略方向非常契合。”周勤透露，阿尔法西格玛未来所有创新产品的国际多中心临床研发都已计划将中国纳入其中。 在阿尔法西格玛的全球研发管线中，还有一系列创新产品等待进入中国市场：包括全球首个特异性逆转剂、首个治疗慢性假性肠梗阻（CIPO）的产品、治疗中轴型脊柱炎的产品等等。 除了创新药品之外，周勤还计划借助中国跨境电商渠道的风口红利，将阿尔法西格玛国际公司管线中，创新型保健品和特医食品引入中国。 03 定人心，开新局 新药研发成本持续攀升，全球制药市场的竞争态势愈发白热化，地缘政治关系亦变幻无常。全球制药行业无疑正处于百年未有的大变局，这也迫使制药企业必须具备高度敏捷的特质。正如周勤所言：“企业不仅要能够精准捕捉转瞬即逝的机遇，还需迅速做出调整，以有效应对市场的不确定性和挑战。” 历经数年变革历程，阿尔法西格玛已然实现了从一家遵循传统阶梯式稳步发展模式的公司，向一家以谋求增长为核心导向的跨国制药企业的重大转型。在此全新发展格局下，无论是战略的精心擘画，还是高效执行，均需保持步调高度协同一致，且具备极为敏锐的市场应变能力。“全球层面已然坚定转型的决心并确立战略布局，中国区亦当全力跟进匹配，以实现协同发展。”但此刻周勤面临的压力，比向总部证明中国新战略更加复杂：上传下达之间，如何重振士气，赢得未来 。 “员工们都能感受到来自市场环境变化的压力，但很多人不清楚未来在哪里，出路在哪里。”周勤敏锐地察觉到，在引领团队迎接变革之前务必使每一位成员深刻认识到变革的关键意义，并对公司的前景满怀信心。就像阿尔法西格玛从全球传导至中国的信念体系：满怀创新热情，大处着眼、小处着手，勇于尝试，团队共创未来。 “人心安稳之要，在于目标既定。”自周勤履新以来，沟通与交流始终贯穿于她的日常工作之中，最近一次的员工调研显示，大家目标明确，对公司未来更有信心了。现有成熟产品所蕴含巨大潜力是未来三年业绩增长的核心抓手；三年之后，新产品将接力续航，助力阿尔法西格玛以创新之姿亮相中国市场。“撸起袖子加油干就是了。” 2024年接近尾声，周勤却还在马不停蹄地奔跑中，构建契合短期与长期目标的组织框架，广纳贤才，已经被她写在了新一年工作的第一项。阿尔法西格玛中国的“马可波罗之旅”正在启航，联通世界，精彩无限。 点击“阅读原文”，了解阿尔法西格玛招聘信息详情 一审| 黄佳 二审| 李芳晨 三审| 李静芝