Danuglipron

iStock, Golden Sikorka Even biopharma’s biggest players have been forced to take a hard look at their businesses and realign their cost structures to cope with the continued and compounding challenges plaguing the industry. In the coming years, Big Pharma will have to reckon with what analyst Mitchell Kapoor calls an “existential risk” to the industry. “Between 2025 and 2030, the pharmaceutical industry has been slated to face a massive $236 billion to $300 billion patent cliff,” with nearly 70 blockbuster drugs slated to lose market protections, the H.C. Wainwright director and senior biotech equity research analyst explained to BioSpace in an email. To protect their bottom-lines, companies across biopharma have been forced to realign their priorities and cost structures, resorting to drastically pruning their pipelines and workforces. By the end of 2024, more than 20,000 jobs across biopharma had been eliminated. That number surged 47% in 2025, with some 42,700 employees laid off across the industry, according to a BioSpace tally, with 2026 not looking much brighter . These are not decisions companies undertake lightly, and they’re not overnight solutions. These reorganization efforts cost millions— maybe even billions —and take months to years of work to execute. But C-suites across biopharma are facing an overlapping series of headwinds that threaten to throw the industry off course, Kapoor said. Patents 5 Pharma Powerhouses Facing Massive Patent Cliffs—And What They’re Doing About It Merck’s Keytruda may be the most talked about drug facing loss of exclusivity but it’s far from the only one, as several of the industry’s top-performers are losing key market protections. Some companies are more prepared than others. February 19, 2025 · 10 min read · Tristan Manalac Read more Indeed, aside from the looming patent cliff, the industry is still in the midst of a protracted post-COVID normalization, Kapoor said, referring to the capital markets. Despite an uptick in dealmaking and IPOs this year, money flowing into drug development will perhaps never match the capital that poured in during the pandemic. Still today, funders are more risk-averse , preferring to throw their dollars behind programs that are more mature and based on more-established science . There are other macro-level factors, too, not least of which are the pricing and policy pressures from the government. Drugmakers also face continued instability at the FDA, complicating drug development timelines. As the storm continues to push the industry around, BioSpace looks at five Big Pharma companies that have enacted sweeping, sometimes-drastic restructuring initiatives to ride it out. Layoffs Biopharmas Axed 47% More Employees Year Over Year In 2025, made or projected biopharma workforce cuts affected about 42,700 employees, according to BioSpace tallies. BioSpace takes a deep dive into which companies and locations were impacted and speaks to experts about what to expect ahead—and why. January 8, 2026 · 5 min read · Angela Gabriel Read more Takeda reels from clinical, commercial setbacks Takeda kicked off a reorganization program in May 2024, with an eye toward “organizational agility, spending efficiencies and leveraging the company’s capabilities in data, digital and technology.” At the time, the Japanese pharma had just suffered a more than 50% hit to its profit. For the fiscal year 2023 (which ran from April 2023 through March 2024), Takeda’s operating profit came out to 214.1 billion yen ($1.3 billion), down from 490.5 billion yen ($3.1 billion) the year prior. In October 2023, the Japanese multinational was forced to pull its lung cancer drug Exkivity from pharmacy shelves worldwide after disappointing findings from a Phase 3 confirmatory study. Later that month, Takeda’s cell therapy Alofisel also failed a late-stage study for Crohn’s perianal fistulas. These back-to-back stumbles resulted in a $770 million write-down for Takeda and a 71% cut to 2023 profit projections. Takeda’s restructuring effort has meant thousands of layoffs across its business. After kicking off the campaign in mid-2024, the company let go of more than 1,500 employees that year. Last month, Takeda announced that 4,500 more workers would lose their jobs during the 2026 fiscal year. Aside from layoffs, the pharma has also made notable changes to its pipeline and drug development strategy. In October last year, Takeda pulled away from cell therapies completely, offloading the programs to an external partner. This move included a headcount reduction of 137. Then in April, the pharma pulled the plug on a dementia drug candidate that had been under development with Denali Therapeutics due to “strategic considerations,” the biotech said in an SEC filing at the time. The partners had also previously been working on an Alzheimer’s disease program that was discontinued in August 2023. Pfizer struggles to regain bearing in post-pandemic market Pfizer was one of the pandemic’s biggest winners, developing the COVID-19 vaccine Comirnaty in collaboration with BioNTech, which in 2021 became the world’s top-selling pharma product with nearly $38.6 billion in revenue. Once the virus hit endemic status, however, market demand for the shot cratered, bringing down Pfizer’s revenues along with it. In October 2023, after suffering quarter after quarter of declining revenues, the pharma launched a “multi-year, enterprise-wide cost realignment program.” The goal, Pfizer said at the time, was to reduce cash burn by $1 billion that year plus an additional $2.5 billion in 2024. In May 2024, the company added $1.5 billion to this savings target through 2027 and in April 2025 raised the bar by $1.7 billion more . Shortly after launching the restructuring, the pharma suffered a series of clinic losses. In December 2023, the company’s former obesity bet danuglipron ran into safety issues, forcing Pfizer to discard its investigational twice-daily regimen for the GLP-1 pill. The pharma pushed through with a daily, modified-release version of the drug, but that formulation was also beset with liver toxicities, ultimately prompting Pfizer to scrap danuglipron altogether. Aside from pandemic and pipeline problems, Pfizer is also facing a strong patent headwind, with the Bristol Myers Squibb–partnered anticoagulant Eliquis set to lose key market exclusivities this year . “Restructuring improves margins, but the market ultimately wants a long-term vision into what replaces the old growth base,” Ram Selvaraju, managing director and senior healthcare equity research analyst at H.C. Wainwright & Co., told BioSpace in an email. For Pfizer, this will involve showing investors that new pipeline bets—built with the bounties of several big-ticket acquisitions, such as the $43 billion acquisition of Seagen and $9.8 billion takeover of Metsera—"can carry more” in terms of generating revenue as the company’s vaccine business finds its post-COVID groove, Selvaraju said. Even with a stacked portfolio, however, Pfizer’s path to recovery looks to be a long one , with the pharma expecting momentum to shift in its favor starting 2029. BMS faces one-two patent punch For Bristol Myers Squibb, a sweeping strategic reorganization and ambitious cost-cutting offered a way to soften the blow from a looming patent cliff. Two of the pharma’s biggest money-makers are set to come under biosimilar attack in the coming years. The Pfizer-partnered blood thinner Eliquis, which last year reigned as BMS’ top-earner with worldwide revenues of $14.4 billion, will lose key protections this year —and its impact on BMS’ topline will be severe. GlobalData in February forecasted that sales of the drug will crash by 15.2% in 2026. Also nearing the end of its exclusivity is the checkpoint inhibitor Opdivo, BMS’s second-biggest product. Opdivo, indicated for a variety of cancers, made $10.05 billion globally in 2025 but is facing key patent expirations in the U.S. by 2028 . In the first quarter of 2024, BMS rolled out a “strategic productivity initiative” aimed at streamlining operations and cutting back cash burn. The pharma set an initial savings target of $1.5 billion through 2025, which would be met by eliminating 2,200 roles across the enterprise. BMS in February 2025 added $2 billion to the cost-cutting goals, to be realized through the end of 2027. Aside from layoffs—of which there have been several rounds —the pharma’s strategic push has also come at the cost of terminated partnerships and culled assets. But BMS’ efforts go beyond simple cost-cutting and includes deals that could position it for greater growth. Just months before unwrapping the strategic campaign, for instance, BMS swallowed neuro specialist Karuna Therapeutics for $14 billion and acquired radiopharma-focused RayzeBio for $4.1 billion . Other partners that the pharma has since brought on via licensing deals include BioNTech and Hengrui Pharma . As in Pfizer’s case, the success of BMS’ reorganization will depend heavily on how well these pickups are executed, Wainwright’s Selvaraju explained to BioSpace in an email. “It means scaling newer growth drivers quickly enough to offset” the impending erosion of the company’s current cornerstone products, he said. Outmaneuvered by main competitor, Novo doubles down on core expertise Just over a year ago, Novo Nordisk’s leadership shocked the industry by ousting former CEO Lars Fruergaard Jørgensen, who had ushered the pharma to a position of global renown with the help of the blockbuster GLP-1 franchise semaglutide. Despite being the first pharma company to market a GLP-1 therapy, the Danish drugmaker has been clinically and commercially outmaneuvered by rival Eli Lilly. Jørgensen’s exit—which the pharma said at the time was precipitated by “the recent market challenges Novo Nordisk has been facing”—would jumpstart a sweeping business realignment initiative. “We need to reallocate and look at our cost base and really put the money where the growth is,” new CEO Maziar Mike Doustdar, told investors during the pharma’s Q2 2025 earnings call. Just over a month later, the Danish giant announced that it would say goodbye to some 9,000 employees across global operations, with the goal of saving roughly $1.25 billion through the end of this year. The layoffs represent a downsizing of Novo’s worldwide headcount by 11%. Novo has also abandoned all work in cell therapy, announcing the pivot less than two weeks after Takeda did the same. Novo at the time said that the savings from all the changes would be “redirected to growth opportunities in diabetes and obesity” as the company tries to minimize Lilly’s lead. Last year, Lilly’s tirzepatide franchise, branded as Mounjaro for type 2 diabetes and Zepbound for obesity, together brought in $36.51 billion . Semaglutide—which includes Ozempic for diabetes, Wegovy for weight loss and the older-generation Rybelsus—earned $36.19 billion. The weight-loss war has now moved to the next phase, waged by oral assets. So far, Novo looks to be well-positioned, with the Wegovy pill once again beating Lilly’s Foundayo to the market—and delivering sales that have exceeded analyst expectations . Merck a ‘good example’ of bracing for cliff Merck is what Wainwright’s Kapoor considers a “good example of how large pharma can defend a franchise without betting on only one answer.” He’s talking about Keytruda, the mega-blockbuster franchise that for three years running has reigned as the industry’s most valuable product. Last year, Keytruda—approved for more than 40 indications—brought in nearly $32 billion . But key market protections for the PD-1 blocker are expiring in 2028, and Merck is bracing for the fall. In July last year, the pharma announced a $3 billion savings campaign through 2027, which has so far involved several rounds of layoffs across its global footprint. Merck intends to put these savings back into its business to support product launches and areas of higher growth. Instead of looking for that one successor to Keytruda, Merck has instead been “building a broader defense” of its business, Kapoor told BioSpace —a strategy that he thinks is a smart way of developing the next phase of the pharma’s pipeline. One area Merck has been investing in is the PD-(L)1/VEGF wave, betting up to $3 billion in November 2024 to partner with Shanghai’s LaNova Medicines. Summit Therapeutics and its Chinese collaborator Akeso shook the field in September 2024 when they claimed victory over Keytruda for the PD-(L)1/VEGF bispecific antibody ivonescimab, touting superior progression-free survival in a Phase 3 non-small cell lung cancer study. But Merck has also been looking at other cancer modalities, particularly ADCs. Merck is working with Kelun-Biotech to advance a combo regimen of Keytruda with the TROP2 ADC sac-TMT in lung cancer. Data earlier this month showed that the doublet achieved a “clear advantage” in overall survival over Keytruda alone, suggesting that the pharma “may be able to defend the Keytruda backbone aggressively with an ADC combination rather than cede the next lung cancer chapter to PD-1/VEGF challengers,” Kapoor said . “That is the kind of portfolio logic large pharma wants right now,” he continued—“multiple shots around a core franchise, not one binary replacement bet.”

【推荐阅读】 百问百答（13）—— 新药研发中的FTO风险：从经典案例看专利合规的生命线 从“减肥神药”到“抗衰新星”：诺和诺德CEO揭秘司美格鲁肽的下一个万亿级野心 PD-1是有限游戏：默沙东靠NSCLC一战定乾坤，插旗完毕，K药称王，但终点已至。GLP-1是无限游戏：礼来与诺和诺德无休止攻防，新靶点、新剂型、新适应症不断外延，边界永在扩张。胜负观分野——前者追求“赢定”，后者信奉“玩下去”。这正是制药业从“重磅炸弹”迈向“健康基建”的范式转移。 2026年6月，全球医药市场呈现出两种截然不同的竞争画面：一边，PD-1的故事已经写到了最后一章——默沙东的Keytruda在绝大多数适应症上完成了“插旗”，BMS的Opdivo沦为第二梯队，后续生物类似药的压力已在眼前，胜负已然尘埃落定；另一边，礼来与诺和诺德在GLP-1领域的厮杀却越发扑朔迷离——没有谁可以宣布胜利，每一季度的市场份额都在剧烈摇摆，新的适应症、新剂型、新靶点层出不穷，战场版图不断外扩。 为什么一个早早有了“答案”，另一个却看不到尽头？答案不在药效数据里，而在于两场竞争归属的根本不同的游戏类型：PD-1战争是一场“有限游戏”，GLP-1战争则是一场“无限游戏”。 这两套底层逻辑，决定了参与者的行动纲领、胜负判定、甚至产业影响的完全差异。而理解这种差异，才能真正看懂当下制药工业正在经历的范式转移。 一、有限游戏的终局：PD-1的插旗竞赛 有限游戏的特征是：边界明确（固定的疾病领域、固定的玩家），规则清晰（临床试验数据决定适应症获批），目标单一（赢）。一旦有人“获胜”，游戏就结束，剩下的玩家只能退场或接受边缘份额。 PD-1战争正是这种游戏的教科书式案例。 默沙东 vs. BMS：胜负手在NSCLC，而非技术代差 2014年，BMS的Opdivo和默沙东的Keytruda几乎同时上市。很多人以为这是一场“双雄对决”，但回头看，真正的分水岭发生在非小细胞肺癌（NSCLC）适应症的争夺上。NSCLC是全球第一大癌种，约占PD-1总市场的40%，谁占据NSCLC一线治疗，谁就锁定了整个PD-1战役的胜利。 BMS的CheckMate-227试验试图用Opdivo联合伊匹木单抗挑战化疗，设计上采用了高选择性的PD-L1分层，且试验终点一度摇摆，最终数据虽然阳性，但获益人群有限，可复制性差；而默沙东的KEYNOTE-189试验走的是K药+化疗 vs 化疗的全人群众路线，设计简洁，数据强劲，一举奠定了K药在NSCLC一线（无论PD-L1表达水平）的金标准地位。 这是一场典型有限游戏的“决胜局”：在规则清晰的竞技场里，临床战略和执行力的优劣直接决定了冠军归属。 此后，默沙东将K药向20多个癌种全面铺开——“插旗”策略：只要一个适应症获批，局面就被锁定，后来者几乎无法翻盘。BMS则在NSCLC、胃癌、食管癌等大适应症的关键节点上接连受挫，最终只能退守膀胱癌、肾癌等相对狭窄的领地。到2020年，Keytruda在PD-1市场的份额已超过60%，胜负判定完毕。 有限游戏的代价：胜者并未赢得无限未来 默沙东赢了有限游戏，但代价是游戏本身也在走向终结。Keytruda专利将于2028年开始到期，适应症已近乎“插满所有旗帜”，增长空间近乎见顶。2025年K药销售额约300亿美元，但市场给出的估值早已充分反映其巅峰——资本追逐的不是已经插满棋盘的玩家，而是那些棋局还在无边界扩张的选手。这也是为什么默沙东市值在2024年被礼来和诺和诺德先后反超的深层原因：有限游戏的赢家收获的是确定的终点，而非无限的可能性。 二、无限游戏的规则：GLP-1的边界持续爆炸 如果说PD-1是一张有限的棋盘，那么GLP-1的棋盘则在不断自我生成。参与者从一开始就意识到：这场游戏没有终局，目标是让游戏永远继续下去。 从减重到NASH再到底层健康干预：适应症不是插旗，而是开新局 2017年，诺和诺德的司美格鲁肽（Ozempic/Wegovy）以GLP-1单靶点降糖上市，彼时谁也没想到它会成为改变人类健康的标杆药物。但无限游戏的第一条规则是：不要固守原有边界。 2021年Wegovy获批减重，将市场规模从糖尿病群体（全球5亿人）扩展到肥胖群体（全球10亿人）；2024年，SELECT试验证实司美格鲁肽的心血管获益，其适应症开始超越代谢本身，进入心衰领域；到2026年，司美格鲁肽和替尔泊肽在NASH、慢性肾病、阿尔茨海默病中的III期数据相继出炉（部分阳性，部分尚在追踪）。每一次新适应症的开辟，不是在固有棋盘上插一面旗，而是在棋盘外新起一局。 礼来的替尔泊肽（Mounjaro/Zepbound）则将这条规则推向极致。作为首个GIP/GLP-1双靶点药物，替尔泊肽在减重效果上直接越过了司美格鲁肽（平均减重22.5% vs 15%），这不仅是一次产品迭代，而是宣布：游戏规则可以被改写，谁说只用一个靶点？ 随后诺和诺德回应以CagriSema（司美格鲁肽+卡格列肽，双靶点），礼来又祭出retatrutide（三靶点：GIP/GLP-1/胰高血糖素），诺和诺德则在冲刺口服单分子GLP-1、以及向更高剂量的安全性玩法。 这场游戏没有稳固的“标准疗法”金位，因为标准不断被自己人推翻。每一方的“领先”不是终局，而是发起下一轮游戏的号令。 产能竞赛：从实验室到全球制造的军备博弈 在PD-1时代，产能从未成为核心竞争力——单抗生产的技术壁垒虽高，但足够少数几个工厂支撑全球市场。然而在GLP-1世界里，需求以亿为单位计算，不再是百万级癌症患者，而是十亿级代谢障碍人群。2024年底，全球GLP-1药物供不应求，美国FDA罕见地将Wegovy和Zepbound列入短缺药物名单。供需缺口使得产能成为无限游戏中排名第一的“延续游戏”的能力。 礼来与诺和诺德在2025-2026年进入了史无前例的工厂建设竞赛：诺和诺德在丹麦和北美投资超200亿美元新建三条灌装线；礼来在德国阿尔泽瑙和爱尔兰利默里克布局口服制剂产能，同时在中国苏州扩大本地化生产。这背后不再是简单的“多卖药”，而是物理性的控制市场：谁先建成足够大的产能，谁就有能力覆盖下一轮新适应症爆发带来的需求浪潮，从而保持游戏的主动权。 递送方式的霸权：剂型也是武器 无限游戏的另一方独特规则是：产品形态可以无限演变，每一次改变都是一次新竞赛的开始。 注射笔、自动注射器、口服片剂、吸入式制剂、经皮贴片——GLP-1的递送方式正在经历一场远超单抗时代的技术革命。诺和诺德2025年推出口服司美格鲁肽（Rybelsus高剂量版），率先打破“必须打针”的认知门槛；但礼来几乎同时将口服替尔泊肽推进关键临床，并通过口服GIP/GLP-1小分子覆盖不用肽类的场景。双方还在针对依从性、进食时间、胃肠道耐受性进行微调，目的不是“谁赢了对手”，而是让更多患者愿意进入这个游戏，从而把市场做大。 三、两种竞争的逻辑对比：从“赢”到“继续玩” PD-1：默沙东靠插旗获胜，BMS插旗失败，游戏结束。 GLP-1：礼来和诺和诺德都在不断开疆拓土，“我是第一”的声明有效期不超过一个临床数据季。 四、无限游戏对制药业的终极启示：从“药”到“生活方式基建” 有限游戏带来重磅炸弹（blockbuster），无限游戏催生“超级平台”。PD-1的价值明确但有限——延长癌症患者生命，市场可以用人均支出×患病人数精确计算。但GLP-1的价值正在从“治疗疾病”向“重构人类代谢健康”迁移，这是一种没有上限的需求。正如2026年的趋势所示，人们开始讨论GLP-1类药物是否能延缓衰老、是否能干预神经退行性疾病、是否能作为青少年体重管理的公共健康工具。当一种药物开始被讨论为“健康管理的基本模块”，它就已经超越了药品的范畴，成为一种基础设施型消费品。 这也是为什么礼来和诺和诺德两家公司可以合计占据全球制药市值近五分之一：市场为无限游戏支付的，不是已经确认的利润，而是游戏将持续扩展的预期。 对后来者：进入无限游戏的入场券变贵了 与PD-1时代不同（后来者仍可通过PD-L1差异化获得一席之地，如罗氏Tecentriq、阿斯利康Imfinzi），GLP-1无限游戏的入场门槛极高——你需要同时具备：多靶点新药研发能力、口服递送技术、全球级制造产能、密集零售渠道、以及对抗消费者心理的品牌建设能力。这就是为什么尽管2026年全球有几十个GLP-1类项目在临床，真正构成挑战的只有安进（潜在口服小分子）、辉瑞（Danuglipron，但副作用问题突出）以及少数中国Biotech，但仍难以撼动双寡头的地位。在一个无限游戏里，先发者不是不可击败，但要击败他们必须玩同一个无限局，而不是只去争夺一个限量的适应症。 结语：游戏的未来取决于玩家选择 2026年6月，如果你问默沙东和BMS的高管，PD-1战争是否结束了？他们会说“竞争格局已定”。但如果你问礼来和诺和诺德的CEO，GLP-1什么时候分出胜负？他们大概率会反问：“为什么要有胜负？” 这正是两种游戏观的根本差异。诺和诺德司美格鲁肽的“先发”被礼来替尔泊肽的“双靶点”超越，礼来的优越的减重数据可能会被诺和诺德的下一代CagriSema或口服方案反击。双方都在确保自己永远不会陷入“已获胜”的满足状态，因为那才是无限游戏的真正危险——以为自己赢了，游戏就结束了。 “有限游戏以为时间可以消灭，无限游戏与时间共存。” 默沙东和BMS讲述了有限游戏的教科书，礼来与诺和诺德则正在书写无限游戏的新章节。而我们这些旁观者，或许正在见证制药业从“治病救人”旧纪元，迈向“人类健康永续”新时代的最关键一步。这场无限游戏，才刚刚开始。 Copyright©2026. All Rights Reserved. 免责声明：本文章内容基于公开信息整理，由AI辅助生成，旨在分享知识，仅供参考，不构成任何专业建议或承诺，不代表本公众号立场。用户须自行甄别所获信息的真实程度及适用条件，并完全承担因使用该信息所引发的一切后果与责任。