Apremilast

No new safety signals observed at Year 5 in the POETYK PSO long-term extension trial, consistent with the established Sotyktu safety profile Following five years of continuous Sotyktu treatment, clinical response was maintained in nearly half of patients for Psoriasis Area and Severity Index (PASI) 90 in the POETYK PSO long-term extension trial PRINCETON, NJ, USA I February 16, 2025 I Bristol Myers Squibb (NYSE:BMY) today announced new five-year results from the POETYK PSO long-term extension (LTE) trial of Sotyktu (deucravacitinib) treatment in adult patients with moderate-to-severe plaque psoriasis. The safety profile of Sotyktu remained consistent through five years with more than 5,000 patient-years of exposure in the trial, with no new safety signals identified. In patients who were treated continuously with Sotyktu , clinical response rates were maintained from Year 1 to Year 5, including Psoriasis Area and Severity Index (PASI) 75, PASI 90 and static Physician’s Global Assessment (sPGA) 0/1 (clear/almost clear). These data were presented at the Winter Clinical Dermatology Conference – Hawaii (WCH) in Big Island, Waikoloa Village, HI taking place February 14-19, 2025. “Today’s findings demonstrate the continued long-term safety and efficacy profile of Sotyktu, with patients maintaining skin clearance over five years,” said Mark Lebwohl, MD, dean of Clinical Therapeutics at the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai and an investigator and paid consultant for Bristol Myers Squibb. “These results further support the role of Sotyktu , the first TYK2 inhibitor available for patients living with moderate-to-severe plaque psoriasis, as a potential oral standard of care.” Clinical efficacy outcomes were sustained in patients who were continuously treated with Sotyktu for PASI 75 (72.1%, Year 1; 67.3%, Year 5), PASI 90 (45.9%, Year 1; 46.3%, Year 5) and sPGA 0/1 (57.5%, Year 1; 52.6%, Year 5). The efficacy analysis included 513 patients who received continuous Sotyktu treatment from Day 1 in the pivotal POETYK PSO-1 and POETYK PSO-2 trials and transitioned to the POETYK PSO-LTE trial, while the safety analysis included 1,519 patients who received at least one dose of Sotyktu during the trials. The patients in this five-year analysis completed 256 weeks of treatment. Efficacy was analyzed using the modified nonresponder imputation (mNRI) method. “These positive five-year results build upon the established profile of Sotyktu , a first-in-class TYK2 inhibitor, as a transformative oral treatment for psoriasis,” said Edgar Charles , MD, vice president and senior global program lead, Early & Late Development Immunology, Bristol Myers Squibb. “As the leader in TYK2 innovation, we continue our relentless pursuit of bold science to elevate new standards of care for the patients we serve.” Sotyktu is approved in numerous countries around the world for the treatment of adults with moderate-to-severe plaque psoriasis. Bristol Myers Squibb thanks the patients and investigators involved in the POETYK PSO clinical trial program. About the POETYK PSO Clinical Trial Program P r O gram to E valuate the efficacy and safety of Sotyktu (deucravacitinib), a selective TYK 2 inhibitor (POETYK) PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) were global Phase 3 studies designed to evaluate the efficacy of Sotyktu compared to placebo and Otezla ® (apremilast), and the safety of Sotyktu, in patients with moderate-to-severe plaque psoriasis. Both POETYK PSO-1, which enrolled 666 patients, and POETYK PSO-2, which enrolled 1,020 patients, were multicenter, randomized, double-blind trials that evaluated Sotyktu (6 mg once daily) compared to placebo and Otezla (30 mg twice daily). POETYK PSO-2 included a randomized withdrawal and retreatment period after Week 24. The co-primary endpoints of both POETYK PSO-1 and POETYK PSO-2 were the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 75 response and those who achieved static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear/almost clear) at Week 16 versus placebo. Key secondary endpoints of the trials included the percentage of patients who achieved PASI 75 and sPGA 0/1 compared to Otezla at Week 16 and other measures evaluating Sotyktu versus placebo and Otezla. Across both clinical trials and timepoints, significantly more S otyktu -treated patients achieved a sPGA score of 0/1, PASI 75 response and PASI 90 response. Responses persisted through Week 52, as 82% (187/228) of patients who achieved PASI 75 with Sotyktu at Week 24 maintained their response at Week 52 in POETYK PSO-1. In POETYK PSO-2, 80% (119/148) of patients who continued Sotyktu maintained PASI 75 response compared to 31% (47/150) of patients who were withdrawn from Sotyktu . Following the 52-week POETYK PSO-1 and POETYK PSO-2 trials, patients could enroll in the ongoing POETYK PSO long-term extension (LTE) trial (NCT04036435) and receive open-label Sotyktu 6 mg once-daily. In the LTE trial, 1,221 patients were enrolled and received at least one dose of Sotyktu . Efficacy was analyzed utilizing treatment failure rules (TFR) method of imputation, along with sensitivity analyses using modified non-responder imputation and as-observed analysis, which have been used in similar analyses with other agents. In addition to POETYK PSO-1, POETYK PSO-2 and POETYK PSO-LTE, Bristol Myers Squibb has evaluated Sotyktu in two other Phase 3 studies in psoriasis: POETYK PSO-3 (NCT04167462) and POETYK PSO-4 (NCT03924427). About Psoriasis Psoriasis is a widely prevalent, chronic, systemic immune-mediated disease that substantially impairs patients’ physical health, quality of life and work productivity. Psoriasis is a serious global problem, with at least 100 million people worldwide impacted by some form of the disease, including around 14 million people in Europe and approximately 7.5 million people in the United States. Nearly one-quarter of people with psoriasis have cases that are considered moderate-to-severe. Up to 90 percent of patients with psoriasis have psoriasis vulgaris, or plaque psoriasis, which is characterized by distinct round or oval plaques typically covered by silvery-white scales. Despite the availability of effective systemic therapy, many patients with moderate-to-severe plaque psoriasis remain undertreated or even untreated and are dissatisfied with current treatments.People with psoriasis report an impact on their emotional well-being, straining both personal and professional relationships and causing a reduced quality of life. Psoriasis is associated with multiple comorbidities that may impact patients’ well-being, including psoriatic arthritis, cardiovascular disease, metabolic syndrome, obesity, diabetes, inflammatory bowel disease and depression. About Sotyktu (deucravacitinib) Sotyktu (deucravacitinib) is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action, representing a new class of small molecules. It is the first selective TYK2 inhibitor in clinical studies across multiple immune-mediated diseases. Bristol Myers Squibb scientists designed Sotyktu to selectively target TYK2, thereby inhibiting signaling of interleukin (IL)-23, IL-12 and Type 1 interferons (IFN), key cytokines involved in the pathogenesis of multiple immune-mediated diseases. Sotyktu achieves a high degree of selectivity by binding to the regulatory domain of TYK2, resulting in allosteric inhibition of TYK2 and its downstream functions. Sotyktu selectively inhibits TYK2 at physiologically relevant concentrations. At therapeutic doses, Sotyktu does not inhibit JAK1, JAK2 or JAK3. Sotyktu is approved in numerous countries around the world for the treatment of adults with moderate-to-severe plaque psoriasis. Bristol Myers Squibb: Pursuing Bold Science in Immunology to Transform Patients’ Lives Bristol Myers Squibb is inspired by a single vision – transforming patients’ lives through science. For people living with immune-mediated diseases, the debilitating reality of enduring chronic symptoms and disease progression can make simple tasks and daily life a challenge. Driven by our deep understanding of the immune system that spans over 20 years of experience, we continue to pursue bold science as we work to deliver life-changing medicines that elevate new standards of care across rheumatology, dermatology and pulmonology. Our sequential immunotherapy research framework aims to address the root cause of disease by controlling inflammation, resetting the immune system and promoting immune homeostasis with the goal of achieving transformational efficacy. By continuously pushing the boundaries of scientific knowledge, we strive to bring forward tailored approaches, treatments and combinations that may lead to durable remissions, improved quality of life and functional cures. Our collaborations with patients, caregivers, healthcare providers and researchers inform our patient-centric approach as we aim to break efficacy ceilings and deliver what matters most – the promise of living a better life. SOTYKTU U.S. INDICATION SOTYKTU ® (deucravacitinib) is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Limitations of Use: SOTYKTU is not recommended for use in combination with other potent immunosuppressants. Please see U.S. Full Prescribing Information , including Medication Guide , for SOTYKTU. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , X , YouTube , Facebook and Instagram . Otezla ® (apremilast) is a registered trademark of Amgen Inc. SOURCE: Bristol Myers Squibb

氨基观察-创新药组原创出品 作者 | 武月 上个月，美国CMS的一纸名单，包括司美格鲁肽、安可坦、安泰坦、全再乐等在内的15款重磅产品，被要求坐上谈判桌。 这场始于《通货膨胀削减法案》（IRA）的降价风暴，正在掀起第二波浪潮。 当美国医保的铁拳，遇上药企的生存本能与新旧政府的权力交替，这场博弈早已超越单纯的价格之争。 IRA被拜登政府视为其美国高药价斗争的关键胜利，而“本届政府绝对不会接受上届政府所做的任何事情”，也构成了IRA最大的政策变数。 就在上任当天，特朗普宣布撤销了拜登政府的一项医保支付新尝试。关于美国令人头疼的高药价问题，特朗普团队也一直公开表态希望能够降价，但对于IRA这项备受争议的政策，特朗普目前尚未表明立场。 保持原有路线，淡化还是全部废除它？没人知道特朗普政府最终会采取哪个方向。毕竟，刚刚上台的特朗普，尚不需要担心民意。 变数之外，唯一确定的是，打压药企、降药价，几乎是美国历任总统的形象工程。 在这样一场政治风暴下，没有哪家药企敢在研发、商业策略上掉以轻心。 / 01 / IRA第二拳 美国医疗保险和医疗补助服务中心（CMS）没有等到特朗普上任后才发布根据《通胀削减法案》谈判的第二份药物清单。 上个月，包括司美格鲁肽在内的15种药物，被列入2027年美国政府医保价格谈判名单。 诺和泰、诺和盈以及诺和忻（成分都是司美格鲁肽），用于Ⅱ型糖尿病和相关并发症，生产商诺和诺德； 全再乐（Trelegy Ellipta），用于慢性阻塞性肺病和哮喘，生产商GSK； 安可坦（Xtandi），用于男性前列腺癌，生产商辉瑞； 泊马度胺（Pomalyst），用于多发性骨髓瘤等，生产商百时美施贵宝； 爱博新（Ibrance），用于某类乳腺癌，生产商辉瑞； 尼达尼布（Ofev），用于成人慢性肺病等，生产商勃林格殷格翰； 利那洛肽（Linzess），用于肠易激综合症和慢性便秘，生产商艾伯维/Ironwood医药； 康可期（Calquence），用于白血病，生产商阿斯利康； 安泰坦（Austedo/ Austedo XR），用于治疗迟发性运动障碍和亨廷顿病，生产商梯瓦制药； 氟替卡松和维兰特罗（Breo Ellipta），用于慢阻肺，生产商GSK/ Theravance； 利格列汀（Tradjenta），用于Ⅱ型糖尿病管理，生产商勃林格殷格翰/礼来； 利福昔明（Salix），用于因旅行或肠易激综合症引起的腹泻，生产商Salix医药； 卡立哌嗪（卡立哌嗪），用于精神分裂症、双相 I 型障碍和重度抑郁症，生产商艾伯维； 西格列汀/二甲双胍（Janumet/Janumet XR），用于Ⅱ型糖尿病管理，生产商默沙东； 欧泰乐（Otezla），斑块型银屑病、银屑病关节炎等，生产商安进。 根据CMS公布的数据，2023年11月至2024年10月期间，约530万美国人使用过这15种药物，Medicare Part D为此支付了约410亿美元，占该报告期内总花费的14%。 如果算上第一批谈判的10种药物，这25款药物占到Medicare  Part D费用的36%。 如此巨额的支出，让我们看到，那些药企梦寐以求的重磅炸弹，正成为联邦医保的“出血点”，所以医保选择了重拳出击。 按照流程，药企需要在2月28日前通知美国政府是否参与谈判，随后参与者会进行为期数月的反复报价和拉锯，最终价格将在2027年生效。 等到这一轮谈判结束后，美国政府将再选择15种药物开始谈判，以此类推。2029年开始，联邦医保谈判的药物将增加到每年20种。 对于药企来说，参与谈判意味着要接受可能的降价结果。第一批谈判药物价格削减幅度在 38%- 79%之间，其中默沙东糖尿病药物Januvia售价从527美元降至113美元，降幅达到79%。 而如果拒绝参与谈判，不仅药品会被联邦医保拒绝覆盖，同时在美国销售这款药物的收入也将面临最高95%的销售税。 难怪辉瑞CEO会大呼，这是“用枪指着你的头进行谈判”。 / 02 / 第一轮降价的涟漪效应 面对医保谈判的压力，大药企早就开始了反抗。 包括辉瑞、诺和诺德、阿斯利康、强生等在内的大药企，纷纷起诉美国政府，但作为弱势一方，最终仍未能阻止IRA的落地。 当然，短时间来看，美国医保的铁拳对药企的影响，并没有想象中那么大。 以第一批占用Medicare Part D资金量最大的Eliquis为例，最终其降价56%。而根据BMS对于Eliquis的销售额预估，2023年报披露的Eliquis销售额为122亿美元，谈判价格出炉后其对2026年-2027年销售额的预估中位数降到98-115亿美元。 悲观情况下，等于Eliquis销售额将减少20%。 56%的降价，对应20%的销售额降幅，这是因为，医保的铁拳未必全部打到药企身上，更重要的是药房福利管理者（PBM）这个中间商。 与我国药品采购实行的“两票制”不同，美国的药物流通过程涉及多个环节和机构，其中PBM扮演着至关重要的角色 尽管PBM不在直接的流通环节中，它们却掌握着审核医生处方、制定处方集、谈判药物价格等多项权力。根据EVERSANA的数据，2017年，美国前三大PBM已经影响了全美73%的处方药销售。 为了增加药物的可及性，药企需要支付给这些主体一定的回扣、折扣等费用作为回报。 并且，这部分费用极其夸张。有数据统计，回扣通常在23%左右。而按照强生此前披露的数据，2022年其支付给这些主体的费用高达390亿美元，占其收入比重为41%，是其净利润的2.17倍。也就是说，回扣比例高达40%。 Eliquis的回扣比例也高达40-49%。这意味着，原本BMS就需要在售价里面掏出很大一部分给中间商PBM，而在IRA医保谈判之后不用再付这些钱了。以Eliquis为例，哪怕是50%以上的降价，其实真正挤压的不是药企，而是中间商。 当然，当那些年销几十亿甚至百亿的重磅产品都可能被纳入谈判，没有哪家药企敢在研发、商业策略上掉以轻心。 因为这颠覆了美国创新药市场，延续数十年的“高定价-长周期”商业模式。医保支付方与制药巨头的力量天平开始倾斜。而对于那些依赖单一爆品支撑的药企，正被迫在创新效率和成本控制间走钢丝。 长远来看，若现行政策持续，IRA谈判降价导致单个产品峰值回报期缩短，到2029年美国前50大药企的峰值产品回报周期将缩短38%。 这种压力正在酝酿一场行业地震，87%的药企正在因IRA的潜在影响而调整产品发布计划。 / 03 / 特朗普时代的变数 当然，目前医保谈判还存在一个巨大的不确定性——美国现任总统特朗普将如何处理拜登的医保谈判政策。 特朗普团队一直公开表态希望降低美国的药品价格，但对于这项备受争议的政策，目前尚未表明立场。 一些人认为，“本届政府绝对不会接受上届政府所做的任何事情”，这也是IRA最大的政策变数。 特朗普在医保政策上一直有着自己的主张。2016年其上台后的第一件事，就是计划废除不痛不痒还加深阶层仇恨的奥巴马医改。只可惜，他失败了。 2021年1月28日，继任者拜登则签署了一系列与医疗保健相关的指令备忘录，称要扭转特朗普造成的“损害”。其中包括推翻了特朗普前政府对堕胎的限制，重启奥巴马医改，这两个话题在美国一直颇有争议，也是民主党与共和两党歧见最深的议题。 IRA，也被拜登政府视为其美国高药价斗争的关键胜利。 这一次，特朗普二次登台后，没有在医疗保健层面动大刀子，但也已经表现出打击拜登政府制定的政策的倾向。 特朗普就任当天，宣布撤销了拜登政府的一项医保新尝试。 CMS曾计划推出CGT准入模型，通过按疗效付费和联邦保险的类带量采购，来降低价格。模型率先试点的产品是Bluebird、Vertex/CRISPR的镰状细胞病（SCD）基因疗法Casgevy（定价220万美元）、Lyfgenia（310万美元）。 如此天价的基因疗法针对的疾病，是一种不成比例地影响美国黑人的遗传性血液疾病。也正因此，CGT准入模型被业内视为一大创新与进步。 特朗普却决定撤销这一新尝试。这也让外界对后续特朗普政府与IRA的走向，有了更多猜测： 保持原有路线，淡化或全部废除它。 当然，大多数行业分析师认为，完全废除的可能性不大。 因为美国的高药价问题，涉及民意。特朗普也曾抨击过美国的药品价格，并提出了一项最惠国政策，即根据其他国家定价。 毕竟，打压药企、降药价，几乎是美国历任总统的形象工程。 上个月底，CMS发表了一份非常简短的声明，简单承认“降低美国人的处方药成本是特朗普总统及其政府的首要任务”，声明还提到“吸取迄今为止的经验教训”和“为谈判带来更大的透明度”。 这或许意味着，一些备受争议的因素，可能会得到改变。 比如，“药丸处罚”，因为小分子只免于谈判9年，而生物制剂的宽限期为13年；再比如，改变谈判的规则和流程，例如CMS与制药商会面的次数，或举行多少次听证会。 不过，拜登政府官员表示，继任者可能无法改变谈判过程，因为法律规定了详细的选择标准。但政治局势风云变幻，特朗普若真有调整动作，势必会引发医药行业和社会各界的强烈反应。 就在2月6日，马斯克带着他的DOGE进驻CMS，并获得管制支付与合同系统的访问权限，审查美国支付系统是否存在欺诈行为。马斯克则在X账号上转发了相关新闻报道，并表示：“没错，这里正是巨额欺诈发生的地方。” CMS作为美国医疗机构的核心，负责管理亿万美国人的医疗保险、医疗补助和其他医疗保健计划，掌握全国每年约1.5万亿美元的联邦预算，占总支出的22%。 DOGE指出：CMS在2023年支付的1000亿美元存在问题。这或许是引发大规模调查的原因之一。 美国医保体系这种冰冻三尺的局面，不论进行任何改革都充满了艰难和未知。更何况，为了争夺利益，两大党之间的斗争一刻未停，大药企以及相关既得利益集团也不会坐以待毙。 接下来，这场大戏，如何唱下去？ PS：欢迎扫描下方二维码，添加氨基君微信号交流。