Mepolizumab

▲AI时代医健领导力跃迁指南作者：贝壳社7月9日，默沙东宣布已与Verona Pharma（简称Verona）达成最终协议，默沙东将通过一家子公司以每股107美元的价格收购Verona的美国存托股票（ADS），交易总价值约为100亿美元。通过此次收购，默沙东将获得Verona的核心产品Ohtuvayre（ensifentrine）。作为一款全球首创的磷酸二酯酶3/4（PDE3/4）抑制剂，Ohtuvayre凭借在单一分子中巧妙融合支气管扩张与非甾体抗炎的双重功效，自2024年6月获批上市后，迅速占据市场，其惊人的初期渗透力及预估的数十亿美元销售峰值，为此次百亿并购提供了坚实的支撑。1应对迫在眉睫的专利悬崖2024年，Keytruda的销售额占默沙东总收入的近46%。鉴于Keytruda的关键专利预计将于2028年左右失效，这一即将来临的‘专利悬崖’已成为近年来默沙东制定重大业务发展战略的核心考量因素。收购Verona并非个例，在此之前，默沙东已于2021年以115亿美元收购了Acceleron Pharma，并于2023年以108亿美元收购了Prometheus Biosciences。默沙东的并购战略已从早期的广泛多元化转变为高度聚焦，专注于肿瘤学以外的特定治疗领域，精准收购低风险且具首创性的资产。近期的一系列收购，如Acceleron、Prometheus和Verona，主要集中在免疫学和心肺疾病领域。从战略视角审视，收购如Ohtuvayre这类已步入商业化阶段的资产，相较于引进早期化合物，具有显著优势。此举可带来即时收益、成熟的供应链体系及真实市场反馈，显著缩短达到销售峰值的时间，并有效降低相关风险。因此，默沙东购买的不仅仅是药物，更是时间和确定性。随着Ohtuvayre的加入，极大地丰富了默沙东日益壮大的呼吸与肺部疾病产品组合。该组合中已包括用于治疗肺动脉高压（PAH）的Winrevair，以及用于预防呼吸道合胞病毒（RSV）的抗体药物Enflonsia。默沙东的目标不仅限于单一药物的收购，而是要在呼吸系统疾病领域构建一个多元化、多机制的产品矩阵。此策略不仅能构筑坚固的竞争防线，还能在商业运作和临床实践中产生明显的协同增效作用。2首创PDE3/4双重抑制剂：OhtuvayreCOPD是一种进行性肺部疾病，尽管市场上已存在多种治疗选项，然而仍有大量患者未能有效控制其症状，持续面临呼吸困难和急性加重的困扰，导致他们的生活质量大幅下降。据估计，在美国，约有120万接受双联或三联疗法的患者病情仍未得到控制。2023年全球呼吸疾病药物市场规模约为320亿美元，其中COPD药物约占50%。COPD市场在过去二十年中，在作用机制上鲜有真正的突破性创新。大多数所谓的“新药”只是将现有药物类别进行组合。然而，一个明确的“未满足需求”人群已经形成：即那些在使用最大剂量的LAMA/LABA/ICS三联疗法后，症状依然持续的患者。这正是Ohtuvayre最初的市场切入点。Ohtuvayre作为全球首个PDE3/4双重抑制剂，是二十余年来首个获批用于COPD维持治疗的新型吸入疗法，标志着该治疗领域的一次重大革新。这种独特的双重作用机制在单一分子中实现了两种关键的治疗效果：支气管扩张（PDE3抑制），通过抑制气道平滑肌中的PDE3，Ohtuvayre能够导致气道松弛和扩张，从而改善气流，使患者呼吸更加顺畅；非甾体抗炎（PDE4抑制），通过抑制肺部炎症细胞中的PDE4，Ohtuvayre能够减少这些细胞的募集和浸润，从而控制驱动COPD病程进展的慢性炎症。体外研究表明，Ohtuvayre还能刺激囊性纤维化跨膜电导调节因子（CFTR），这可能有助于改善黏液纤毛清除功能并降低黏液粘度。对于伴有慢性支气管炎的患者而言，这一特性可能带来额外的临床获益。该药物通过标准的喷射雾化器直接递送至肺部。这种给药方式最大化了药物在肺部的暴露量，同时最小化了与口服PDE抑制剂相关的全身性副作用，从而在疗效和安全性之间取得了更好的平衡。Ohtuvayre的双重作用机制直接弥补了当前COPD治疗模式的一个核心缺陷，即通常需要联合使用不同的药物（如支气管扩张剂和吸入性皮质类固醇）才能达到类似的效果。这使其有潜力成为一种基础性治疗药物，而不仅仅是又一个“me-too”类的附加疗法。当前，对症COPD患者的标准治疗方案通常涉及双联、三联，这意味着患者需要同时服用来自不同药物类别的、具有多种作用机制的药物。Ohtuvayre在单一非甾体分子中结合了支气管扩张和抗炎作用，形成差异化优势。随着针对特定炎症通路的生物制剂的获批，COPD市场开启了新的竞争篇章。Dupixent由赛诺菲和再生元共同开发，获欧盟委员会批准用于患有病情不受控制的慢性阻塞性肺病（COPD）患者的附加维持治疗，成为首个用于COPD的生物制剂。Dupixent是一种IL-4/IL-13抑制剂，适用于具有嗜酸性粒细胞表型的患者。在特定的慢性阻塞性肺病（COPD）患者亚群中，Dupixent可将急性加重减少30%～34%。Nucala由葛兰素史克开发，是一种IL-5抑制剂，适用于嗜酸性粒细胞型慢性阻塞性肺病（COPD）患者的辅助维持治疗。在MATINEE试验中，显示可将急性加重减少约21%。而Ohtuvayre不依赖于特定生物标志物，其主要市场定位是针对那些持续存在症状（如呼吸困难）并需要改善支气管扩张和非甾体抗炎效果的广大COPD患者。财务数据显示，Ohtuvayre销售额从2024年的4230万美元，飙升至2025年第一季度的7130万美元，季度环比增长高达95%。Verona一直在积极探索ensifentrine在其他慢性呼吸系统疾病中的应用，这为默沙东带来了巨大的潜在增值空间。其中关键在研适应症，如非囊性纤维化支气管扩张症（NCFB）、哮喘、囊性纤维化（CF）。此外，ensifentrine与LAMA类药物格隆溴铵的复方制剂正在开发中，这有望提供一种单一产品解决方案。小结：通过此次收购，为默沙东锁定了一项风险可控、已进入商业化阶段、具有差异化作用机制且通往重磅炸弹药物地位路径清晰的资产，解决其最紧迫的战略脆弱性——Keytruda的专利悬崖问题。然而，要完全实现这100亿美元投资的价值，默沙东必须成功应对复杂的竞争格局，并成功将Ohtuvayre的适应症扩展至未来其他领域。往期推荐1医健企业前沿动态2医健行业BD/出海/投融资洞察___*声明：本文仅为作者观点，不构成任何投资建议，且非治疗方案推荐素材来源官方媒体关于贝壳社贝壳社是国内领先的医健创新创业服务平台，构建了"产业空间+创业教育+投资孵化+资本运作"四位一体服务体系，为医健领域创业企业提供全周期赋能。通过深度挖掘高成长项目、精准匹配产业资源及全球化生态网络，覆盖企业从孵化培育到加速发展的全链路，重点提供包括空间落地、创业培训、资本运作及跨境资源链接服务。贝壳社以加速科学技术成果转化与产业升级为目标，致力于成为医健领域的孵化器、加速器、连接器。

For the third time in the last five years, Merck has pulled off an acquisition in the $10 to $12 billion range, buying out Verona Pharma and its potential COPD blockbuster Ohtuvayre. Merck has pulled off another acquisition which fits in its “sweet spot,” as described by CEO Rob Davis, paying $10 billion for Verona Pharma and its potential blockbuster Ohtuvayre, a first-in-class treatment for chronic obstructive pulmonary disorder (COPD).It is the second-largest deal in biopharma this year, ranking behind Johnson & Johnson’s $14.6 billion buyout of Intra-Cellular, and fits Merck’s pattern of striking every other year with a major transaction.In 2021, Merck spent $11.5 billion for Acceleron and its pulmonary arterial hypertension (PAH) treatment, now known commercially as Winrevair. Then in 2023, the New Jersey company ponied up $10.8 billion for Prometheus and its late-stage bowel disease candidate PRA023.The acquisitions are designed to compensate for the expected loss of patent protection later this decade for cancer superstar Keytruda, which generated $29.5 billion in sales in 2024, accounting for 46% of the company’s revenue.“The sweet spot we see is that $1 to $15-billion range,” Davis said in conference call on Wednesday. “As we’ve also consistently indicated, we’re willing to go beyond that for the right opportunity.”Additionally, Davis said that the company plans to launch roughly 20 “new growth drivers in the coming years, almost all of which have blockbuster potential.” He added that Merck will continue to scout out oncology, immunology and cardiometabolic assets through business development.As for the buyout of Verona, Merck has agreed to pay $107 per share, which is a 23% markup on their price at market close Tuesday and a 39% premium on their 60-day volume-weighted average price. The companies expect the deal to close in the fourth quarter of this year.The FDA approved Ohtuvayre 13 months ago as the first novel inhaled treatment for COPD in more than two decades. The drug can be used as a monotherapy or as an add-on medicine with current steroid therapies. As a selective dual inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes, Ohtuvayre combines two properties in one medicine, setting it apart from COPD competitors for its ability to both open the airways of patients and reduce their inflammation.Ohtuvayre is off to a solid launch, generating sales of $71 million in the first quarter of this year, good for 95% growth sequentially. During the three months, 25,000 prescriptions were filled, up from 16,000 in 2024.“Since launching Ohtuvayre in August 2024, we have seen rapid and accelerating uptake in the U.S.,” Verona CEO David Zaccardelli said in a release Wednesday. “We believe Merck’s commercial footprint and industry-leading clinical capabilities will help accelerate the potential of Ohtuvayre to reach more patients living with COPD.” The treatment has not been approved in Europe. Some of that advantageous footprint comes through Merck’s commercialization of Winrevair. Although it is a product for a rare lung disease, many of the physicians who prescribe Winrevair will have patients with COPD.The prescriber base for the disease is 14,500 in the U.S., according to Merck’s human health president Jannie Oosthuizen. Verona reported in April that 5,300 doctors had prescribed Ohtuvayre in the first quarter.“I think our scale brings a good ability to expand fairly rapidly into that broader prescriber base, educate and get Ohtuvayre to be added to existing background therapies, especially in those patients with persistent symptoms,” Oosthuizen said, adding that the company expects the market to grow from $17 billion this year to $27 billion by 2032. Meanwhile, other companies are rushing to the COPD space. After a delay, the FDA in May approved GSK's antibody drug Nucala as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype. Amgen and AstraZeneca have hopes for their asthma drug Tezspire as a potential COPD treatment.Last year, Regeneron and Sanofi gained approval for Dupixent to treat COPD exacerbations. The companies also have a second COPD candidate in IL-33 inhibitor itepekimab, which is being tested in two phase 3 trials.