Rivaroxaban

关注并星标CPHI制药在线 减肥药开发是医药行业目前最大的热点之一，甚至有分析机构预测，减肥药市场未来的规模将发展到2000亿美元的水平，几乎可以和目前的肿瘤学产品比肩，因此众多生物医药和科技公司都渴望跻身这个拥有巨大开发潜力的市场之中。诺和诺德的减肥药Wegovy今年第三季度获得了25亿美元的销售业绩，预计明年将拿下130亿美元的全球销售额，并一举跻身重磅炸弹前十名的榜单。在这样一片大好的局面下，即便诺和的Wegovy和礼来的Zepbound把持了目前减肥药市场的绝大部分市场，但仍然有一干减肥药开发商抱着“野芳虽晚不须嗟”的信念在开发减肥药的道路上大干快上。而在另一块平行战场上，减肥药项目和企业的收购竞争也在经历激烈的明争暗斗。 最新的大热收购目标是12年前创立的总部位于加州圣迭戈的Viking Therapeutics。 Viking Therapeutics 的口服多肽减肥药 VK2735 在 1 期临床试验中表现出较高的有效性和安全性，吸引了行业的广泛关注。VK2735 是一种双重 GLP-1/GIP 受体激动剂。在其I期研究中，受试者的体重显著下降，并且VK2735表现出了良好的安全性和耐受性。在 100 mg 的最高剂量组中，VK2735 实现了安慰剂调整后28天6.8%的减重率，这个数据令行业侧目。众多分析师在看好VK2735未来的同时，也纷纷认为Viking Therapeutics将成为制药业巨头收购的下一个热点。 Viking没有稳定的资金注入，独自完成VK2735上市的目标稍显艰巨，尤其是考虑到口服版本的研究仍然处于I期，皮下注射的临床也只是II期，因此需要大量资金的注入才有可能实现产品的上市。之前Viking似乎一直处于“待价而沽”的状态，等待的似乎就是关键里程碑的实现。而如今I期口服制剂数据的出炉似乎就是最好的时机，因此Viking的收购成为了越来越接近现实的交易。 包括辉瑞和阿斯利康在内的多家大型公司在内，他们收购减肥药资产或公司的意愿早已不是秘密。阿斯利康从中国Eccogene Inc.（诚意生物）收购的GLP-1减肥药资产AZD5004恰好也是一款口服制剂，但不同于VK2735，AZD5004是一款小分子药物。阿斯利康也在近期的ObesityWeek 2024会议上公布了AZD5004的I期数据，显示出5.8%的四周减重率。因此阿斯利康继续收购口服减肥药资产的意愿可能没有那么强烈。而辉瑞在终止了其小分子GLP-1口服减肥药资产lotiglipron之后，又终止了另一款口服小分子减肥药danuglipron每日两剂的临床研究，目前只剩下danuglipron的每日一剂肥胖症项目，因此收购意图可能更为强烈。 除了Viking Therapeutics之外，作为“收购靶点”的公司还包括下列减肥候选药资产拥有者： Structure Therapeutics • 总部：美国加州南旧金山 • 成立时间：2021年 • 市值（2024年11月6日值，下同）：22亿美元 • 主要减肥药资产：Aleniglipron（又名GSBR-1290口服GLP-1受体激动剂），II期数据公布 • 收购看点：Aleniglipron的II期数据与礼来小分子口服GLP-1减肥候药orforglipron可比（12周安慰剂调整后减重率6.2%），但停药率可能较低。小分子口服药具有明显的成本优势，因此代表了减肥药开发的下一波热点。那些拥有口服减肥药资产，且已经产生了不错临床中后期数据的中小公司必然会成为收购重点。 • 收购阻碍：开发位置看上去至少落后orforglipron一年。在机制相同、疗效相近、模态一样的情况下，时间线决定了未来的市场地位和如今的收购价值。 Altimmune Inc. • 总部：美国马里兰州Gaithersburg • 成立时间：1997年 • 市值：5.1亿美元 • 主要减肥药资产：Pemvidutide（每周注射一次多肽GLP-1/胰高血糖素双受体共激动剂），III期研究中。 • 收购看点：长期减重率略优于Wegovy。2.4 mg pemvidutide 48周减重率15.6%。Pemvidutide同时对代谢障碍相关脂肪型肝炎（MASH）进行临床研究。 • 收购障碍：20% 的停药率可能是一个限制因素，但随着患者进入第 3 阶段，允许剂量减少，这应该会对耐受性所有帮助。 Zealand Pharma • 总部：丹麦哥本哈根 • 成立时间：1999年 • 市值：87.6亿美元 • 主要减肥药资产：Survodutide（每周注射一次的多肽GLP-1/胰高血糖素双受体共激动剂），III期临床进行中，授权勃林格殷格翰开发；Dapiglutide（GLP-1/GLP-2共激动剂），II期进行中；Petrelintide（胰淀素类似物），II期进行中。 • 收购看点：Zealand Pharma将根据survodutide全球销售额获取10%左右的版税；项目已经进入III期，有望成为首批Wegovy和Zepbound的挑战者；46周19%减重率；针对MASH开发获得FDA突破性疗法头衔；同时拥有新颖机制的GLP-1/GLP-2双受体共激动剂中期资产，以及胰淀素激动剂中期资产petrelintide。Zealand Pharma在不久前的ObesityWeek 2024会议中公布了petrelintide的I期数据，引发了广泛关注。多次递增剂量 I 期试验数据显示，在16周每周注射一次（剂量分别为 2.4 mg, 4.8 mg 和 9.0 mg）后，平均体重减轻 4.8%、8.6% 和 8.3%，而合并安慰剂组减轻 1.7%。这显示了petrelintide不仅在机制上能够填补目前减肥药的空白，在实际疗效上可能也具备了未来与semaglutide和tirzepatide分庭抗礼的潜力。美国银行分析师表示，他们预计petrelintide将主要用于 GLP-1 不耐受或失败市场（约占 20% 的患者），并预计其年销售额将达到 80 亿美元的峰值。 • 收购障碍：自身被收购意愿可能较低，但Zealand Pharma已经表达出了正在寻找共同开发petrelintide的合作伙伴的动态。与授权survodutide的模式不同，Zealand Pharma将参与petrelintide的开发与商业化的整个过程。Zealand Pharma的CEO表示，目前已就petrelintide的潜在合作开发与前十大制药企业中的一家产生了关联，但不肯透露更多的消息。 Fractyl Health • 总部：美国马萨诸塞州Burlington • 成立时间：2010年 • 市值：1.1亿美元 • 主要减肥药资产：Revita（一种门诊内窥镜手术，通过热液消融持久改变十二指肠功能障碍，从而恢复代谢健康。有证据表明，Revita 可能为肥胖和 2 型糖尿病患者提供持久的体重维持和改善血糖控制。针对接受 GLP-1 药物治疗体重至少减轻 15% 并希望停止使用 GLA-1 药物而不反弹的患者进行临床研究）；Rejuva （一种新型局部给药 AAV 基因疗法，目前处于临床前开发阶段，可改善胰岛功能。通过改变患者的胰腺胰岛细胞中的代谢激素反应，实现持久的体重减轻和 2 型糖尿病的长期缓解。） • 收购看点：提供长期体重管理的方案 • 收购障碍：特殊治疗后产生的不良反应 潜在肥胖症资产和公司买家 • 默沙东（收购意愿：高）：默沙东的药王Keytruda将在2028年专利到期，默沙东对代谢类疾病表现出了高度兴趣，但缺乏GLP-1管线资产。 • 诺和诺德（收购意愿：高）：诺和诺德一直在通过资产购买的方式巩固自己在代谢疾病领域的领先地位。 • 辉瑞（收购意愿：中/高）：辉瑞一直在努力开发口服减肥药，但屡遭挫折。目前几乎硕果仅存的GLP-1小分子减肥候选药daniglupron的前景并不被看好，因此在此路不通的情况下，辉瑞可能选择外部资产的引入。 • 强生（收购意愿：中/高）：近期代谢疾病领域的挫折（Xarelto, Invokana, aprocitentan）大大刺激了强生通过收购外部资产的渴望。 • 礼来（收购意愿：高）：与诺和诺德的减肥药“军备竞赛”。 • 阿斯利康（收购意愿：中/高）：从中国Eccogene Inc.（诚意生物）收购的GLP-1减肥药资产AZD5004令阿斯利康在减肥药竞赛中处于了一个有利的位置。阿斯利康透露出减肥药与Farxiga设计联合疗法的强烈愿望。 • 勃林格殷格翰（收购意愿：高）：BI对于代谢疾病疗法开发具有很高兴趣，其survodutide是从Zealand Pharma获取授权的资产，因此拥有一款独立的减肥药资产对于BI有着强大的吸引力。 • 罗氏（收购意愿：中/高）：最近从Carmot收购GLP-1资产显示了罗氏对开发减肥药的兴趣。罗氏并不算充盈的减肥药管线昭示着可能会有更多的收购项目到来。 • 第一三共（收购意愿：中）：尽管代谢类疾病曾经是第一三共的开发重点，但其目前的核心资产是肿瘤学产品。 • 赛诺菲（收购意愿：中）：赛诺菲的开发中心已经转移到了炎症和免疫产品，但历史上对于代谢疾病的开发可能重燃赛诺菲进军肥胖症的热情。 • 诺华（收购意愿：中）：虽然拥有不少代谢疾病资产，但诺华的核心竞争力在于肿瘤学、免疫学和罕见疾病。 Ref. Malone, E. Top 10 Drugs Q2 2024: Mounjaro Comes Roaring In. Skyrizi Also Makes Its Debut. Scrip. 24. 10. 2024. Structure Therapeutics Reports Positive Topline Data from its Phase 2a Obesity Study and Capsule to Tablet PK Study for its Oral Non-Peptide Small Molecule GLP-1 Receptor Agonist GSBR-1290. Structure Press Release. 03. 06. 2024. Boehringer Ingelheim to advance survodutide into three global Phase III studies in obesity. BI Press Release. 17. 08. 2023. Obesity Drugs: The Next Wave of GLP-1 Competition. New drugs from public and private companies will challenge Novo and Lilly's dominance. Morningstar & PitchBook. Sept. 2024. END 【智药研习社线上研习会报名】 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

When Johnson & Johnson backed down from its proposal to modify the way it supplies certain drugs under the 340B statute, it hinted litigation could be its next step to effect changes that address what it says is rampant abuse of a program originally intended to make medicines more accessible to underserved patients. The pharmaceutical giant has now taken that legal step. J&J is suing the Department of Health and Human Services and the Health Resources Services Administration (HRSA), which administers the 340B program. In a 51-page complaint filed in federal court on Tuesday, the pharmaceutical giant contends its plan to offer drugs under a rebate plan is legally permissible, and that HRSA’s determination otherwise is unlawful. The pharmaceutical giant is now asking the court to make a legal determination. Neither HHS nor HRSA responded to a message seeking comment about the lawsuit. Sponsored Post The Future of Hospitals and Pharma Companies Will Depend on Strength of Healthcare Analytics Insights PurpleLab® stands out from others in this sector by providing its data analytics services to several different groups of users across healthcare and pharma companies. By Stephanie Baum The 340B program allows eligible hospitals and clinics serving low-income and underinsured patients to purchase outpatient medications. When the program was conceived in 1992, a key goal was to uninsured and underserved patients access important medicines at a reduced cost. Drugs have been procured under a discount model. The healthcare entities covered under the statute purchased medications at discounts that can amount to 50% or more off of the list price. J&J argues that the 340B program has been overtaken by for-profit entities, including pharmacy chains and pharmacy benefit managers “who have exploited the program for profit.” Though the 340B program was implemented to improve access to medicine, J&J argues that covered entities have turned the program into a source of revenue, making money by getting full insurance reimbursement for drugs they purchased at discounted 340B prices. The pharma company also flagged duplicate discounts—getting the 340B price on the same drug purchase that also receives a Medicaid rebate. “Put simply, what was intended as a buy-low/sell-low program for vulnerable patients has turned into a buy-low/sell-high commercial business opportunity disconnected from its public health mission,” J&J said in the complaint. “This is the opposite of how charity care should be funded: the 340B Program creates incentives to provide services to insured patients rather than those vulnerable populations most in need of affordable care.” To support its claims, J&J points to reports from government watchdog groups that found covered entities are profiting from reduced-price medications but failing to pass on those discounts to patients. The drugmaker also notes that HRSA audits have found many covered entities were non-compliant with the 340B program. J&J said audits it has sought to uncover more abuse have been stonewalled. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health Disagreement over the 340B program has been simmering for years. Matters came to a head more recently when J&J sent an August letter notifying 340B participants that in mid-October, the pharma giant would shift from discounts to rebates for two drugs, the blood thinner Xarelto and the plaque psoriasis medicine Stelara. Under this rebate plan, hospitals would need to purchase these drugs at full price and then later submit data to the company in order to receive a rebate reflecting the discounted 340B price. The rebate proposal sparked opposition from hospital groups and lawmakers. In letters to J&J, HRSA Administrator Carole Johnson stated that under the 340B statute, the J&J rebate plan would require approval from the Secretary of HHS. Johnson’s Sept. 27 letter noted that the company had not requested such approval. That letter also warned J&J that proceeding with the rebate plan would lead to termination of the company’s pharmaceutical pricing agreement and possibility of monetary penalties. In October, J&J halted its plan to implement rebates, explaining HRSA’s threat to terminate the company’s participation in the 340B program would only hurt patients. But J&J did not back down from its position that changes to the program are necessary. In its suit, J&J argues it is well within its rights to offer a rebate program. The company says the statute states HRSA may direct a company to a particular pricing mechanism only through that company’s pharmaceutical pricing agreement with the agency. Because J&J’s agreement contains no such direction or requirement, the company says it has full discretion to choose the pricing mechanism, and the mechanism it is choosing is rebates. J&J contends changing to a rebate model would provide transparency, mitigating the duplicate discounts that are violations of the 340B statute. J&J also contends rebates are the only mechanism it is aware of that would enable the company to meet its obligations under the Inflation Reduction Act (IRA). This law requires a drugmaker to offer the covered entities either the 340B ceiling price or the act’s maximum fair price—whichever is lower. J&J says a rebate model would enable the company to comply with the IRA’s prohibition of duplicate discounts. J&J filed the suit in the U.S. District Court for the District of Columbia. The case number is 1:24-cv-3188.