Apixaban

Can Eli Lilly escape the boom-and-bust cycle that has long defined the pharma business? In January, Lilly CEO David Ricks was on stage with Nvidia CEO Jensen Huang. Ricks had recently (if briefly) joined the trillion-dollar club, a rarefied set of corporate chiefs whose companies have touched or exceeded that stratospheric valuation. Huang, a longtime member, wears it with the relaxation of his ever-present leather motorcycle jacket. Ricks, more often found in a sport jacket, is new to the club. To keep his spot, Ricks is trying to do what no pharma company has succeeded in. He needs to turn the windfall from Lilly’s massive success in weight loss into building a pipeline — and new technological approaches — that’s so broad, so forward-looking and so lucky, that he defies the gravitational pull of blockbuster patent expiries that reliably hauls down every high-flying drugmaker. On stage with Huang at an Nvidia event in San Francisco, Ricks called it achieving “exit velocity.” To do that, Lilly has undertaken a range of unusual ideas that could leave an impact on the biopharma ecosystem. While it’s busy building out its weight loss franchise with additional assets, it’s also partnering with Nvidia on a new AI-powered discovery lab , constructing an industry-leading supercomputer , offering an AI model-for-data swap to biotechs, leaning heavily into direct-to-patient sales , and partnering with the VC firm a16z on a new biotech fund . If it all works, Lilly could not only redefine the boundaries of drug company economics, but leave its stamp on the broader healthcare system itself. If it fails, the company — and Ricks — could end up redefining the meaning of “the bigger they are, the harder they fall.” “Lilly has a blend of exuberance and confidence of being the first trillion-dollar pharma combined with the paranoia and anxiety of sitting on what will become the biggest patent cliff in the industry’s history,”said Elliot Hershberg, who helps lead biotech investing at the VC firm Amplify Partners. He added that he views Lilly as playing on a different chessboard than the rest of the drugmaking giants. Ricks has brought an obsession with speed to Lilly, driven perhaps by his own memories of how quickly financial fortunes can turn. It has experienced two crushing patent cliffs, one with Prozac in 2001 and another with Zyprexa in 2011, that left the company as one of the industry’s least loved, until its recent success hauled it to new heights. Ricks called speed the most important element to improving R&D, therefore boosting Lilly’s future beyond today’s weight loss successes. The key patent for the main ingredient in Mounjaro and Zepbound won’t expire until 2036, but when that time comes, the loss could be enormous. “The challenge before us now is, how do we find another success cycle before that one runs out — hopefully a lot sooner than when it runs out,” Ricks told Huang, “and sort of get exit velocity. There’s really no major company in our industry that’s done that.” Ricks joined Lilly’s marketing department in 1996. He went from running the Canadian market to the Chinese market, eventually becoming CEO in 2017. In his first performance management review as the company’s leader, he was told he had an “overdeveloped sense of urgency.” That’s trickled down to the rest of the 50,000-employee company. “We have an impatient CEO,” Lilly’s chief information and digital officer Diogo Rau said in an interview, when asked about the collaboration with Nvidia. The companies are building a first-of-its-kind Bay Area laboratory that will physically co-locate scientists from both organizations to work on a range of AI moonshots in biopharma. The arrangement started with texts between Ricks and Huang last year. The goal is to open the Bay Area lab by the end of March, Rau said, a far faster speed than most big pharma companies typically build. Rau departed Apple to join Lilly in 2021. Some ex-Apple folks who followed him have told him they’re amazed by “how fast we move here,” he said. The speed means a lot of deals. Ricks said at his JPM presentation the business development team averaged a deal every nine days in 2025, totaling 39 on the year — far more than any other rival company. Many of these deals are a bit out-there compared to the standard, pipeline-stuffing tendency of large drugmakers. Some are higher-risk projects, like Verve’s cholesterol-lowering gene editing program or Ventyx’s inhibitors against NLRP3 , a target tied to aging-related diseases. Others, like the lab with Nvidia and bankrolling the a16z fund, are structured in ways even further divorced from the aim of bringing in specific drugs to boost revenue. Absent are any big, late-stage deals. Rau said the underlying driver is a willingness to “make bets on things we have high conviction on.” “We don’t necessarily require a brute financial case that might take three months to build,” Rau said. “We’ve learned from our past decisions that we regret more the things that we haven’t done or moved quickly on than the things we have done.” One of its first deals of 2026 was with Chai Discovery , an AI startup developing some leading protein design models. Its co-founders said the Lilly team was in its San Francisco office the week after it released details on its Chai-2 model last summer. Just a few months later, they became Chai’s first announced pharma partner. “They’ve just run through all sorts of walls to get the approvals they needed to make this happen really quickly,” Chai co-founder Jack Dent said in an interview. “That’s going to pay massive dividends for them. Other companies may want to take note.” Pharma peers, by comparison, seem like they’re treading water. Sanofi has struggled to answer what comes next after Dupixent, recently ousting Paul Hudson as CEO. Merck and Pfizer have made a flurry of expensive deals and major restructurings to brace for their own upcoming patent expiries on key drugs like Keytruda and Eliquis, which are expected before the end of this decade. Lilly has the chance to pursue a different fate. That will likely require hitting on some of the big-swinging ideas that could unlock huge patient populations, if successful. Those include a cholesterol-lowering gene editing program, large Alzheimer’s prevention studies, and non-opioid pain medications in the pipeline. “They’re incredibly ambitious, long-term thinkers,” a16z general partner Vineeta Agarwala said in an interview. “I do not think they are chasing patent cliffs.” It also hasn’t led to empire building, or a loss of discipline. Ricks says he has tried to keep headcount flat, and Lilly’s headcount grew by about 3,000 people, or 6%, over the last year, even as its revenue grew by 45% last year. He weighs in on all new hires and promotions above a certain level. “That makes me very unpopular,” he said on a recent podcast, an unusual, free-flowing two-hour-long conversation that sounded more like the loose, tech-cool Huang than the typical pharma CEO. “People are like, ‘How do I get this work done?’” The comparison extends to its market valuation, which makes Lilly look more like a Silicon Valley tech darling than a drugmaker. Lilly has kept a frenetic pace since the JP Morgan conference, when Ricks was on stage with Huang. They have given hints of what could be the next piece of the obesity story, in combination trials with some of its other drugs like Taltz that appear to boost efficacy in conditions like psoriasis. Outside of obesity, the first weeks of the year have included partnerships on gene editing and immunology, an acquisition of an in vivo CAR-T therapy, a sweeping R&D deal with a Chinese biotech powerhouse, and the announcement of a new Allentown, PA factory alongside Gov. Josh Shapiro. The unavoidable fate of pharma looms around every corner: Look no further than the downfall of its chief GLP-1 rival Novo Nordisk. In May, Lilly will celebrate its 150th anniversary. Next year, Ricks will celebrate his 10-year anniversary in the CEO job. For now, he and the company are on top. The real question is how long they can stay there.

175年，这个数字在制药行业意味着什么？ 意味着它经历了抗生素的诞生、见证了癌症治疗的革命、也扛过了新冠疫情这场席卷全球的风暴。 意味着当大多数竞争对手还在纸上画蓝图的时候，辉瑞已经把药送进了几代人的身体。 它叫辉瑞（Pfizer）。医药圈有个称号送给它——“宇宙第一大药厂”。 戏谑，但也是事实。 刚从谷底爬上来，就已经不一样了 要了解现在的辉瑞，得先理解它经历了什么。 新冠疫情让辉瑞登上了历史巅峰——2022年，营收突破1003亿美元，成为全球首家年收入破千亿的药企。然后，随着疫情退潮，Paxlovid和疫苗的销售断崖式下跌。2023年，营收直接腰斩至585亿美元，跌幅41%。 外界很多声音在说：辉瑞要不行了。 但这家公司用2024年的财报给出了回答：2024年全年，辉瑞非新冠产品运营收入实现了12%的强劲增长。  没有依赖新冠红利，靠自己的管线爬了回来。 430亿美元，换来的是什么 2023年底，辉瑞做了一件当时被很多人质疑的事：以430亿美元收购Seagen，确立了其在抗体偶联药物（ADC）领域的全球领导地位。  430亿美元。什么概念？这是一笔足以让整个生物医药圈颤抖的赌注。 但一年后，这笔钱的回报开始显现。Seagen旗下多款ADC产品在2024年贡献了超32亿美元营收：Nectin-4 ADC药物Padcev营收达15.88亿美元，CD30 ADC药物Adcetris营收10.89亿美元，HER2 ADC药物Tukysa创收4.80亿美元。  ADC，全称抗体偶联药物，被称为”生物导弹”——用抗体精准找到癌细胞，再用小分子毒素定点爆破，在最大化杀伤肿瘤的同时，尽可能减少对正常细胞的误伤。这是当下全球肿瘤治疗中最热的技术方向之一，而辉瑞通过这笔收购，一步跨进了第一梯队。 管线：超过100个项目，这是什么规模 很多人对”研发管线”这个词没有直观感受。 打个比方：你是一家餐厅，厨房里同时在做多少道菜，决定了你的上限。辉瑞的厨房里，现在同时在做一百多道。 截至2025年初，辉瑞拥有超过100个临床开发项目，管线呈现健康的漏斗形态：Phase 1阶段46个项目，Phase 2阶段30个项目，Phase 3阶段28个项目，另有4个项目正处于注册申请阶段。  更关键的是效率。辉瑞报告称，其新分子实体从首次人体试验到获批的成功率在2024年提升至21%，显著高于行业平均水平的10%左右。  做100个项目里有21个能走到终点，在这个行业已经是顶尖水准。制药研发的失败率之高，是很多人难以想象的——大多数公司进了10个项目，能有1个上市就烧高香了。辉瑞靠什么做到21%？更严格的早期筛选机制，和对生物标志物的广泛应用。简单说：它在更早的时候就知道哪些项目该砍，不会把钱烧在注定失败的方向上。 几个值得细看的管线方向 毫无疑问，肿瘤学仍是重中之重！ 辉瑞整体的肿瘤管线主要关注三大方向：小分子靶向药物、大分子靶向药物（主要是双特异性抗体），以及抗体偶联药物（ADC）。  2025年，肿瘤学领域的Atirmociclib（CDK4抑制剂）、Sigvotatug vedotin等重要项目有望取得进展。 这些名字现在可能陌生，但在肿瘤治疗领域，CDK4抑制剂代表的是乳腺癌治疗方向的前沿迭代，值得持续关注。 还有一个不得不提的：博瑞纳®（洛拉替尼）——全球首个且唯一的第三代ALK抑制剂，CROWN研究最新数据显示其中位无进展生存期超过5年，是迄今为止所有转移性实体肿瘤中单药靶向治疗最长的PFS，树立了晚期肺癌靶向治疗新标杆。 5年，这个数字在晚期肺癌治疗里是什么概念——几年前，这类患者的中位生存期可能连2年都不到。 GLP-1：一盘没有弃局的棋 GLP-1减肥药是当下最热的赛道，诺和诺德、礼来几乎垄断了市场话语权。辉瑞此前在这一赛道有过挫折，但辉瑞并未放弃，目前正聚焦于Danuglipron的每日一次缓释剂型研究，其逻辑是：口服小分子GLP-1药物相比注射剂具有依从性优势，若能解决耐受性问题，仍有巨大市场空间。  能不能成，现在还是问号。但在一个潜在市场规模数千亿美元的赛道上，辉瑞不会轻易走人。 心血管与罕见病：稳健的现金牛 罕见病氯苯唑酸类药物（Vyndaqel系列）2024年销售额达54.51亿美元，同比增长高达64%。 这款用于治疗转甲状腺素蛋白相关心肌病的产品，正在成为辉瑞新的重磅炸弹级产品。 对中国：不只是卖药，是要”共成长” 辉瑞在中国深耕已超过36年。但2025年前后，它和中国的关系发生了质变——从单向输入变成了双向合作。 去年，辉瑞与三生制药完成了一笔震动全行业的交易：辉瑞支付12.5亿美元不可退还首付款，以及最高可达48亿美元的里程碑付款，获得三生制药PD-1/VEGF双抗SSGJ-707的全球独家开发权。整个交易潜在金额超过60亿美元，刷新了国产创新药对外授权历史纪录，也是中国创新药授权史上首个超过10亿美元首付款的交易。  这意味着什么？辉瑞在用真金白银告诉整个行业：中国的创新药，值这个价。 与此同时，辉瑞承诺向中国投入10亿美元总投资，推进”辉瑞中国2030战略”，目标之一是”三倍速中国创新”，并已累计斩获30项创新药及新适应症上市批准。  2025年10月，辉瑞研发开放创新中心正式启幕，为中国本土高校、创新生物技术企业、医院和临床研究机构提供专业支持，聚焦转化和临床开发，依托辉瑞的国际化人才优势赋能本土研发。  这已经不只是”外资药企在中国卖药”的故事，而是一家全球性公司试图深度嵌入中国医药生态的战略布局。 老大哥，有老大哥的方式 专利悬崖是制药行业每家大公司都无法回避的宿命。辉瑞面临2025年至2030年间包括Eliquis和Ibrance在内的重磅产品专利到期带来的约170亿美元收入风险。  但辉瑞应对这个问题的方式，不是等待，也不是慌乱，而是，用一笔430亿美元的并购提前布局ADC，用一百多个管线项目构建纵深，用10亿美元投注中国市场，用两位数的临床成功率建立研发壁垒。 175年的药企，见过的风浪不计其数。它知道怎么穿越周期。 专利悬崖不是终点，管线才是。 老大哥的底气，从来不是过去赚了多少钱，而是未来还有多少牌可以打。 辉瑞手里的牌，还有很多！