Sotatercept

▎药明康德内容团队编辑降低重大发病和死亡风险76%，默沙东公布“first-in-class”疗法3期临床结果默沙东（MSD）今天首次展示了3期临床试验ZENITH的结果，该试验评估Winrevair（sotatercept）与安慰剂相比，治疗高死亡风险肺动脉高压（PAH）成人患者的效果。这些患者同时接受最大耐受剂量的背景PAH治疗。数据显示，在中位随访时间为10.6个月时，Winrevair与安慰剂相比将重大发病和死亡事件（包括全因死亡、肺移植以及与PAH恶化相关住院≥24小时）的相对风险降低了76%（HR=0.24，95% CI：0.13-0.43；单侧p<0.0001）。接受Winrevair治疗的患者中有17.4%（n=15/86）经历了一次或多次重大发病和死亡事件，而安慰剂组则为54.7%（n=47/86）。ZENITH试验中Winrevair的安全性基本与先前研究中观察到的一致。Winrevair是一款“first-in-class”的IIA型激活素受体（ActRIIA）融合蛋白。它将ActRIIA经过改造的细胞外域与抗体的Fc端融合在一起，可以阻断激活素与细胞膜上的受体结合，从而降低激活素介导的信号传导。在临床前实验中它可以逆转肺动脉壁和右心室的重塑。它在2024年3月获得美国FDA的批准，用于治疗肺动脉高压。礼来siRNA疗法降低遗传性心血管疾病风险因子水平近94%礼来（Eli Lilly and Company）日前宣布了在研疗法lepodisiran的2期临床试验积极结果。Lepodisiran是一种小干扰RNA（siRNA）疗法，旨在降低心脏病遗传风险因子脂蛋白（a）——Lp（a）的产生。在2期临床试验ALPACA中，最高剂量（400 mg，每半年一次）的lepodisiran，在治疗后的60至180天期间，将患者Lp（a）水平平均降低了93.9%，达到了试验主要终点。接受16 mg和96 mg剂量的患者在相同时间段内分别实现了40.8%和75.2%的Lp（a）水平降低。此外，接受400 mg的lepodisiran治疗的患者，在第30至360天期间平均Lp（a）水平下降94.8%，并在第360天仍比基线低91.0%，在第540天（约1.5年）比基线低74.2%。超80%患者LDL-C达标，阿斯利康口服PCSK9抑制剂2期结果积极阿斯利康（AstraZeneca）今日公布了在研疗法AZD0780在2b期临床试验PURSUIT中的积极结果。与安慰剂相比，在标准治疗他汀药物基础上使用AZD0780时，显著降低患者的低密度脂蛋白胆固醇（LDL-C）。AZD0780是一种每日口服的PCSK9抑制剂，针对那些尽管接受标准降脂治疗（如他汀类药物），但未达到LDL-C降低目标的患者。在12周时，在他汀治疗基础上添加AZD0780（30 mg，每日一次）使LDL-C降低50.7%（95% CI：-59.0%，-42.4%；p<0.001）。无论受试者在基线时接受中等或高强度他汀剂量，均观察到类似疗效。此外，AZD0780使84%的受试者达到美国心脏协会/美国心脏病学会指南推荐的LDL-C目标值（<70 mg/dL），而仅接受他汀治疗的受试者中只有13%达到该目标值。降低癌症复发风险32%，阿斯利康重磅免疫疗法再获FDA批准阿斯利康今日宣布，其重磅免疫疗法Imfinzi（durvalumab）联合吉西他滨和顺铂作为新辅助治疗，随后在根治性膀胱切除术后单药作为辅助治疗，已获美国FDA批准用于治疗成人肌层浸润性膀胱癌（MIBC）患者。该批准基于3期临床试验NIAGARA的结果。在该试验中，患者在根治性膀胱切除术前接受了四个周期的Imfinzi联合新辅助化疗，随后接受八个周期的Imfinzi单药治疗，对照组仅接受根治性膀胱切除术前的新辅助化疗。在预定的中期分析中，基于Imfinzi的围手术期方案与对照组相比降低了疾病进展、复发、未接受手术或死亡风险32%（HR=0.68，95% CI：0.56-0.82；p<0.0001）。Imfinzi组的估计中位无事件生存期（EFS）尚未达到，而对照组为46.1个月。关键次要终点总生存期（OS）结果显示，与根治性膀胱切除术前新辅助化疗相比，基于Imfinzi的围手术期方案使死亡风险降低了25%（HR=0.75，95% CI：0.59-0.93；p=0.0106）。口服司美格鲁肽降低主要不良心血管事件风险14%，已递交监管申请诺和诺德（Novo Nordisk）日前发布了SOUL心血管结局试验的完整结果，该试验评估了Rybelsus（司美格鲁肽）14 mg片剂，在降低患有2型糖尿病合并动脉粥样硬化性心血管疾病（ASCVD）和/或慢性肾病（CKD）患者的主要不良心血管事件（MACE）风险方面的效果。这项随机双盲、平行分组、含安慰剂对照的心血管结局试验共招募9650名患有2型糖尿病及ASCVD和/或CKD的成人患者。试验达到主要终点，口服司美格鲁肽与安慰剂相比使MACE风险降低14%（HR=0.86，95% CI：0.77-0.96；P=0.0055）。主要终点为从随机分组到首次发生主要不良心血管事件（包括心血管死亡、非致命性心肌梗死或非致命性中风）的时间。基于SOUL试验的数据，诺和诺德已提交Rybelsus的标签扩展申请，目前该申请已被美国FDA受理，预计将在2025年作出审评决定。Rybelsus片剂是一种每日一次的胰高血糖素样肽-1（GLP-1）受体激动剂，用于在2型糖尿病成人患者中联合饮食和运动改善血糖控制。推动AI药物设计，Isomorphic Labs完成6亿美元融资Isomorphic Labs今天宣布，其首次对外融资轮已筹集6亿美元。此次融资由Thrive Capital领投，GV参与投资，并有现有投资者Alphabet的后续资金跟进。这笔投资将加速Isomorphic Labs在前沿人工智能（AI）研发方面的进展，迅速推动该公司下一代AI药物设计引擎的发展。Isomorphic Labs成立的目标是利用AI的强大力量重新构想并加速药物发现，为全球数百万患者带来急需的治疗。该公司旨在应用其开创性的AI药物设计引擎实现生物医学突破，并在多个治疗领域和药物模式中推进药物设计项目。自成立以来，该公司已开发出多种下一代AI模型，这些模型共同构成了其AI药物设计引擎。其中一个突破性模型是AlphaFold 3，该模型于2024年5月由Isomorphic Labs与Google DeepMind联合开发并发布，能够准确预测所有生命分子的结构和相互作用。借助这些先进的AI技术，Isomorphic Labs已建立了一个药物发现管线，包括与礼来和诺华（Novartis）的合作项目，以及主要聚焦于肿瘤学和免疫学的内部研发项目。▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] WINREVAIR™ (sotatercept-csrk) Reduced the Risk of a Composite of All-Cause Death, Lung Transplantation and Hospitalization for Pulmonary Arterial Hypertension (PAH) by 76% Compared to Placebo in the Phase 3 ZENITH Trial. Retrieved March 31, 2025, from https://www-merck-com.libproxy1.nus.edu.sg/news/winrevair-sotatercept-csrk-reduced-the-risk-of-a-composite-of-all-cause-death-lung-transplantation-and-hospitalization-for-pulmonary-arterial-hypertension-pah-by-76-compared-to-placebo-i/[2] IMFINZI® (durvalumab) approved in the US as first and only perioperative immunotherapy for patients with muscle-invasive bladder cancer. Retrieved March 31, 2025, from https://www.businesswire.com/news/home/20250331589590/en/IMFINZI-durvalumab-approved-in-the-US-as-first-and-only-perioperative-immunotherapy-for-patients-with-muscle-invasive-bladder-cancer[3] Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. Retrieved March 31, 2025, from https://www-nejm-org.libproxy1.nus.edu.sg/doi/full/10.1056/NEJMoa2501006[4] Lilly's lepodisiran reduced levels of genetically inherited heart disease risk factor, lipoprotein(a), by nearly 94% from baseline at the highest tested dose in adults with elevated levels. Retrieved March 31, 2025, from https://investor.lilly.com/news-releases/news-release-details/lillys-lepodisiran-reduced-levels-genetically-inherited-heart[5] AZD0780, a novel oral PCSK9 inhibitor, demonstrated significant LDL cholesterol (LDL-C) reduction in PURSUIT Phase IIb trial. Retrieved March 31, 2025, from https://www.astrazeneca.com/media-centre/press-releases/2025/azd0780-a-novel-oral-pcsk9-inhibitor-demonstrated-significant-ldl-cholesterol-ldl-c-reduction-in-pursuit-phase-iib-trial.html[6] Isomorphic Labs announces $600m external investment round. Retrieved March 31, 2025, from https://www.isomorphiclabs.com/articles/isomorphic-labs-announces-600m-external-investment-round[7] Oral semaglutide 14 mg demonstrated superior reduction in risk of cardiovascular events in late-breaking SOUL trial presented at the American College of Cardiology. Retrieved March 31, 2025, from https://www.prnewswire.com/news-releases/oral-semaglutide-14-mg-demonstrated-superior-reduction-in-risk-of-cardiovascular-events-in-late-breaking-soul-trial-presented-at-the-american-college-of-cardiology-302414854.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

iStock, Jolygon Merck continues to build the case for the pulmonary arterial hypertension drug that won FDA approval in 2024. In high-risk patients with pulmonary arterial hypertension, Merck ’s fusion protein therapeutic Winrevair reduced the likelihood of major morbidity and mortality by 76% in the Phase III ZENITH trial. Analysts at Guggenheim Partners called this outcome “striking” and “very impressive” in a note to investors Monday, pointing to improvements in key secondary outcomes in overall survival and transplant-free survival. The Guggenheim analysts also pointed out that Winrevair had “relatively consistent improvements” in mortality and morbidity across patient subgroups, including age, sex and disease subtype and severity. In November 2024, Merck announced that, following the recommendations of an independent data monitoring board, it was stopping ZENITH ahead of schedule due to “ overwhelming efficacy .” On Monday, the pharma revealed that in the Winrevair arm, 17.4% of patients experienced at least one major morbidity or mortality event, as opposed to 34.7% of placebo comparators. The data were presented at the 2025 American College of Cardiology’s Annual Scientific Session and Expo and simultaneously published in The New England Journal of Medicine . Winrevair is a recombinant activin receptor type IIA-Fc fusion protein that targets and binds to activin A and other ligands that belong to the TGF-β superfamily. This mechanism of action allows Winrevair to restore balanceto vascular proliferation, a key pathway that is altered in pulmonary arterial hypertension (PAH). In particular, PAH patients see high excessive cell proliferation in key arteries, leading to thickened blood vessel walls and, in turn, impaired blood flow. Winrevair was approved by the FDA to treat PAH in March 2024, making it the first-ever drug for the disease that targets activin signaling. Merck continues to build its evidence base for Winrevair. In March 2023, the pharma unveiled full data from the Phase III STELLAR trial, touting a 40.8-meter improvement in 6-minute walk distance in patients with PAH following treatment with the drug. Winrevair also cut the risk of death or clinical worsening by 84% versus placebo. Merck is also running the Phase III HYPERION study to assess the benefit of Winrevair when used with background therapy. In January 2025, the company ended the trial ahead of schedule , in line with the recommendations of an external committee, because of strong efficacy findings in an interim analysis. Results from HYPERION will be presented later this year, according to Merck’s Monday announcement.