Mizuho Bank Ltd.

Pfizer inked settlement agreements with Dexcel Pharma and Cipla around patent disputes concerning generics to its blockbuster tafamidis. As Pfizer gears up to defend its patents on transthyretin amyloid cardiomyopathy (ATTR-CM) med tafamidis in court this week, eleventh-hour settlements with two of the three generic drugmakers involved could bode well for both the New York pharma and its competitor BridgeBio, analysts say. Pfizer’s legal action against Dexcel Pharma was dismissed without prejudice late last week, an April 24 filing from a Delaware district court shows. By April 25, Cipla had settled as well, with the Delaware court also dismissing Pfizer’s legal action “without prejudice,” Evercore ISI analysts explained in a note.Dexcel, a private Israeli generics maker, had a slightly different angle in the case as the only one that had already admitted infringement of Pfizer's 441 tafamidis patent, while the litigation involving Cipla and Hikma covers patent infringement and invalidity, Leerink analysts pointed out in an April 24 note to clients. Further details surrounding the settlements remain unclear, with the specific year of generic entry that the drugmakers agreed on unknown. However, any date after 2030 or 2031 would be a “huge relief” to Pfizer’s business, the Evercore team notes.  In all three cases, Pfizer is claiming infringement on its ‘441 patent, which is set to expire in August 2035. Given that Cipla and Hikma asserted the same claims, Mizuho Securities analysts figure that the Cipla settlement “increases the likelihood” that a Hikma settlement will follow as well.  Pfizer sells tafamidis only as high-dose Vyndamax in the U.S., after pulling its lower-dose version, Vyndaqel, from the market last year. The company’s tafamidis franchise racked up worldwide sales of $6.3 billion in 2025, reflecting 17% growth from 2024, which helped offset slower COVID sales across Pfizer’s larger product portfolio. Pushing off generics to Pfizer’s blockbuster heart med is in BridgeBio’s interest as well. The company sells a rival oral TTR stabilizer called Attruby. BridgeBio’s stock is trading at $76.56 as of publication time Monday morning, rising 4.5%. “While several unknowns remain, including settled-upon launch date and implications for other generic filers, we see resolution of tafamidis IP overhang as a clearing event for BBIO shares, which would bring large institutional investors off the sidelines against of 2026/27 launches in achondroplasia, ADH1, and LGMD2i,” Leerink analysts wrote, referring to BridgeBio’s other pipeline prospects. When one of Pfizer’s tafamidis patents was revoked in Europe earlier this year, BridgeBio’s stock plunged 15% in turn as investors feared earlier generic competition to the medicine could put pricing pressure on Attruby. As Leerink Partners analyst Mani Foroohar, M.D., told Fierce in an interview, the availability of generics to an established drug player is “typically a headwind to reimbursement, especially in European markets, where you have comparability pricing.”  Still, other analysts called the stock move an overreaction, with Jefferies analyst Andrew Tsai noting at the time that Attruby is becoming a first-line ATTR-CM option that could be differentiated from Vyndamax and that the BridgeBio drug is in line for 2034 peak sales of $4 billion to $5 billion.Attruby garnered sales of $362 million in 2025. As of Feb. 20, 2026, 7,804 prescriptions had been written for the drug since its late 2024 launch, according to BridgeBio. The launch momentum was attributed to its “differentiated profile as the only near-complete stabilizer on the market, continued prescribing growth, repeat use, and patient persistence that has exceeded our expectations,” chief commercial officer Matt Outten said at the time. At launch, BridgeBio priced its med at $18,759 for a 28-day supply, or about $244,000 annually. Pfizer similarly charges some $268,000 for its Vyndamax before discounts per year. 

“我们的新药可能像他汀一样改变世界。” 2024年，BioAge Labs刚在纳斯达克上市没多久，肥胖药azelaprag的临床二期（Phase 2）数据就崩了，股价跟着崩。一家刚IPO的生物科技公司在最热的赛道上交出最冷的数据，这种故事在制药行业每个季度都要上演几遍。 然而不到两年后，2026年4月21日，同一家公司的新闻稿里竟然出现了这么一句话：“NLRP3 inhibition could have transformational potential, much as statins did for LDL cholesterol decades ago.”翻译一下：我们的新药可能像他汀一样改变世界。 他汀是目前全球最核心、应用最广的降脂药，也是心脑血管疾病二级预防的基石药物。如果真能像他汀一样改变世界，背后的经济效益不言而喻。那么BioAge Labs说出这句话的底气是什么呢——临床实验中，15个肥胖受试者，吃了21天BGE-102，高敏C反应蛋白（hsCRP，一个反映全身炎症水平的指标）降了86%。 86%确实是一个惊人的数字 图注：BioPharma Dive对BGE-102数据的行业分析报道 | 图源：biopharmadive.com 先说清楚，这个数据本身是真的好。 BGE-102是一种NLRP3抑制剂。NLRP3炎症小体则是炎性衰老（inflammaging）研究里的明星靶点，随衰老过度激活，驱动慢性炎症，和心血管疾病、神经退行性疾病一堆东西都有关联。经常被提到的hsCRP是衡量这种慢性炎症的一把标尺。 BGE-102在I期临床试验里做到了什么：60mg剂量组15个人，吃21天，结果hsCRP中位数降了86%。87%的受试者（15人中的13人）hsCRP恢复到2 mg/L以下——这是临床上认定的"正常"水平。 更夸张的是，60%的人（15人中的9人）降到了1 mg/L以下。1 mg/L以下意味着什么？这些原本处于高炎症状态的肥胖受试者，体内的炎症水平降到了健康人的范围。 同时IL-6降了55-78%，纤维蛋白原降了20-30%。药物耐受性良好，没有严重不良事件。 并且120mg剂量组14人吃14天的数据和60mg组基本持平——说明低剂量就够了。 放在整个NLRP3抑制剂赛道里看，这组数据可能确实是best-in-class。BioAge有理由兴奋。 但I期临床试验数据好看，跟真的成为下一个他汀，是两码事。 一个成功了的失败实验 图注：STAT News报道——BGE-102早期数据显示抗炎潜力 | 图源：statnews.com 2017年，心血管领域发生了一件大事：诺华的CANTOS试验结果出来了。 CANTOS试验用的是canakinumab（商品名Ilaris），一种直接靶向IL-1β的单克隆抗体。IL-1β正是NLRP3激活后释放的关键促炎因子。试验就一个思路——把高心血管风险人群的炎症水平打下去，看心梗和中风会不会少。 结果：心血管事件减少了15%。 抗炎可以降低心血管风险，这个假说第一次在大型随机对照试验中得到了验证。《华盛顿邮报》称之为"对抗心脏病的全新可能"。 然后故事翻转了。 Canakinumab在降低心血管事件的同时，增加了致死性感染的发生率。免疫系统被压制后，细菌趁虚而入。试验数据显示，canakinumab组的感染致死率是安慰剂组的1.7倍（每百人年0.31 vs 0.18）。 总死亡率没有统计学差异——心血管死亡少了，感染死亡多了，一增一减，打了个平手。 诺华看到这份数据后，选择不做了。一种需要皮下注射、每季度一次、每年费用数万美元的生物制剂，降了心血管事件却增了致死感染，从商业角度看完全走不通。 CANTOS给后来者留下了两笔遗产。第一笔是希望：抗炎确实能降心血管风险，方向是对的。第二笔是警告：抗炎的代价可能是感染，而这个代价足以杀死一个药物项目。 BioAge新闻稿里没说的那些话 回到BGE-102的新闻稿。 BioAge的CMO Paul Rubin在新闻稿中写道：此前的抗炎干预试验数据表明，将hsCRP降到2 mg/L以下，与主要心血管不良事件减少25%相关。 他几乎肯定引用的是CANTOS的数据——准确说是CANTOS数据的一个亚组分析。hsCRP降到2以下的那部分患者，心血管事件减少了25%。这个引用本身是准确的。但CANTOS数据的另一半——致死感染增加、总死亡率无改善、诺华弃赛——新闻稿里只字未提。 一家上市公司的新闻稿选择性引用有利数据，这当然不违法，甚至不违规。所有制药公司都这么干。但当你把一个失败案例的成功面拿出来，作为自己产品的论据，同时隐去那个失败案例失败的原因，读新闻稿的时候，得自己把另一半补上。 BioAge的回应逻辑是：两种药的机制不同。Canakinumab直接阻断IL-1β这个细胞因子，不分来源地全部拦截——但IL-1β的来源不止NLRP3一条通路，免疫系统的正常防御也需要它，全拦就等于连友军一起打了。BGE-102只关闭NLRP3这一个产生IL-1β的开关，其他通路不受影响。选择性更高，理论上对正常免疫的干扰更小。 这个推理在逻辑上说得通。但它是纯理论推导。目前没有任何临床数据证明NLRP3抑制剂比IL-1β抗体更安全。BGE-102的I期临床试验只有29个人、最长给药21天——这个时间窗口根本不够暴露感染风险。致死感染的信号通常要在几百人、随访数月甚至数年的试验中才会浮现。 29个人，21天。记住这两个数字，因为接下来我们要看看资本市场基于这两个数字给出了什么估价。 图注：BioAge Labs (BIOA) 纳斯达克股价走势 | 图源：Google Finance 赛道已经被资本定过价了 2026年1月，Eli Lilly宣布以12亿美元收购Ventyx Biosciences——另一家NLRP3抑制剂开发商。罗氏（Roche）和诺和诺德（Novo Nordisk）此前也在这个赛道做了投资布局。 投行Mizuho Securities的分析师估计，NLRP3抑制剂仅在肥胖适应症上的年销售额就可能超过100亿美元。逻辑是NLRP3药物可以和GLP-1类减肥药联合使用，帮助减少炎症和肌肉流失。 12个月之内，NLRP3从一个学术圈里讨论了十几年的靶点变成了资本宠儿。 这里面有一个因果倒置：Lilly花12亿买Ventyx，部分原因是看好NLRP3的前景；Mizuho给出100亿市场估计，部分依据是Lilly愿意花12亿。资本的热情在给自己的热情定价。 这个游戏在制药行业有个专门的名字，叫"validation by acquisition"（一家公司的技术、产品或商业模式的价值，被行业巨头 / 头部资本的收购行为所背书与证实）。 BioAge的CEO把BGE-102叫做"pipeline in a pill"——一颗药搞定多个适应症。第二期心血管试验计划2026年上半年启动，同时还要做糖尿病黄斑水肿的早期混合临床阶段，然后是中枢神经系统（CNS）方向。 一个刚做完I期临床试验的药物，同时瞄准三个治疗领域，确定不是PPT战神？ 可能两者都有。数据确实好看，故事也确实需要讲。一家刚从azelaprag失败中爬出来的公司，需要一个足够大的叙事来恢复市场信心。而"pipeline in a pill"这四个词，对投资者的杀伤力可能比86%这个数字还大。 被淹没在hsCRP光环下的信号 图注：NLRP3炎症小体结构与功能 | 图源：Wikipedia 说一个所有报道都忽略了的数据：新闻稿和所有媒体报道的焦点都在hsCRP——降了86%，数字足够惊人，适合做标题。但BGE-102同时把纤维蛋白原降了20-30%。纤维蛋白原是一个独立的心血管风险因子，它直接参与血栓形成。降低纤维蛋白原意味着血液的凝血倾向降低，理论上可以减少血栓相关的心血管事件。 这个数据被hsCRP的光环完全盖住了。如果后续试验能验证纤维蛋白原的降低转化为临床获益，BGE-102就不只是在降炎症——它同时在降血栓风险，两条腿走路。 他汀用了20年 图注：BioAge Labs官网首页 | 图源：bioagelabs.com 他汀类药物的故事始于1970年代，日本生化学家远藤章从桔青霉中分离出了第一个HMG-CoA还原酶抑制剂。1987年第一款他汀洛伐他汀上市，1994年4S试验证明他汀降低了冠心病患者的死亡率，此后他汀逐步成为心血管二级预防的基石药物。 从发现到成为标准治疗，他汀走了大约20年。 BGE-102现在的位置：15个人吃了21天。 这两个时间尺度之间的落差，是理解这个故事的关键。方向可能是对的，CANTOS已经替所有后来者趟过了最难的那一步——证明抗炎确实和心血管获益相关。NLRP3抑制剂在理论上也确实有可能比canakinumab更安全。BioAge的I期临床试验数据在同类药物中可能确实是最好的。 但从15人到他汀之间，还有Ⅱ期临床试验的剂量摸索、Ⅲ期临床试验的大规模验证、感染风险的长期观察、监管审批、定价谈判……这中间任何一步都可以出错。毕竟CANTOS已经演示过一次"方向对了、最后一步翻车"的故事。 BioAge计划2026年下半年拿到Ⅱ期临床试验数据，2027年启动Ⅲ期临床试验准备。如果一切顺利——这六个字在制药行业是最昂贵的假设——最早也要到2029年以后才可能有Ⅲ期临床试验结果。 在那之前，整个NLRP3赛道的百亿估值建立在一个推论上：因为抗炎方向是对的，所以NLRP3抑制剂一定比canakinumab好。 这个推论可能成立。但目前支撑它的全部临床证据加起来，就是不到30个人、最长吃了21天药、看的还是替代终点。 Lilly花12亿美元，至少买了Ventyx完整的临床数据包和专利组合。BioAge现在手里有的，是一组漂亮的I期临床试验数据和一个极其激进的叙事。 两者之间的距离，可能就是接下来两三年这家公司命运的全部故事。 编辑：时光抗衰产业观察 运营：菠萝蜜星球原住民 从市场前沿到资本布局，国内外长寿产业动态全覆盖，点击下方公众号卡片，关注「时光抗衰产业观察」，一站式了解长寿产业： 参考来源 [1]BioAge Labs官方新闻稿，2026年4月21日 [2]BioPharma Dive报道，Kristin Jensen，2026年4月21日 [3]STAT News报道，Elaine Chen，2026年4月21日 [4]Ridker PM et al., "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS)," NEJM 2017 [5]Wikipedia: Canakinumab, NLRP3, Inflammaging [6]Nature Reviews Immunology: "The NLRP3 inflammasome: molecular activation and regulation to therapeutics," 2019

Dive Brief:A three-drug combination involving Merck & Co.s Welireg failed to significantly delay tumor progression or extend survival in a Phase 3 trial of patients newly diagnosed with the most common form of kidney cancer, setting back the big drugmakers plans to further expand use of the medication.The study evaluated Welireg alongside Mercks immunotherapy Keytruda and Eisais Lenvima in first-line clear cell renal cell carcinoma and compared that regimen to the Keytruda-Lenvima tandem alone. Merck didnt provide specifics, but said that drug trio as well as a separate one also tested in the trial missed the studys dual main objectives at an interim analysis.Merck noted how the findings dont affect other ongoing studies in Litespark, the broad program its jointly conducting with Eisai and that includes other Welireg tests. The Food and Drug Administration is reviewing an application based on results from one Litespark study that would expand use of Welireg earlier in kidney cancer. Still, Merck shares fell by about 4% Tuesday.Dive Insight:Welireg is an important part of Mercks plan to absorb the coming losses when Keytruda, the companys top moneymaker, loses patent exclusivity.Acquired through a buyout of Peloton Therapeutics in 2019, Welireg blocks a protein called HIF-2 alpha thats known as a primary driver of clear cell renal cell carcinoma. Since then, the drug has racked up approvals in a rare genetic condition, an uncommon adrenal tumor and, importantly for Merck, made headway into advanced kidney cancer.Those clearances have made Welireg one of Mercks faster-ascending medicines and a highlight in its strategy to hit $70 billion in annual sales by next decade. Welireg sales grew more than 40% in 2025, surpassing Wall Street expectations to reach $716 million for the year. Anticipated label expansions into the second-line and post-surgery settings should drive revenues even higher.Yet Tuesdays study result significantly lowers the drugs financial ceiling. To Leerink Partners analyst Daina Graybosch, the failure takes Mercks upside case for filling the Keytruda revenue gap in the early 2030s off the table. Consensus estimates have projected about $2.2 billion in global sales for Welireg in 2030. But success in first-line kidney cancer could have unlocked $5.8 billion in overall revenue potential given how long patients stay on therapy when Welireg works, Graybosch wrote.The setback could have implications for others, too. Arcus Biosciences is developing a rival HIF-2 alpha medicine in kidney cancer and, by the end of the year, intends to start a Phase 3 trial in the first-line setting. Mizuho Securities analyst Salim Syed noted that Arcus medicine may be a superior molecule based on earlier data. The regimen Arcus is expected to test is also different, sparing use of a tyrosine kinase inhibitor like Lenvima that may add toxicity, Syed wrote.Weliregs failure leaves a potential [first-line] opening for Arcus drug, casdatifan, added Cantor Fitzgeralds Li Watsek.Arcus shares ticked up about 2% Tuesday. '