Dalzanemdor

iStock, RomoloTavani These deals radically reshaped the biopharma world, either by one vaccine rival absorbing another, a Big Pharma doubling down after another failed acquisition or, in the case of Pfizer and Novo, two heavyweights duking it out over a hot obesity biotech. 2025 proved to be a high-drama year for dealmaking as pharmas fought over companies, swallowed their rivals and found inspiration in other companies’ transactions. The biggest deal of the year—Johnson & Johnson’s $14.6 billion buy of Intra-Cellular all the way back in January—didn’t even make the list of what BioSpace editors consider the most influential M&A deals of the year. While the year won’t go down as the biggest in value by any means, some of these deals will have an indelible impact on the industry for years to come. Pharmas dealt in obesity, cancer, cell therapy, mental health and a slate of others, growing and expanding their businesses. These deals, such as Pfizer’s fight to get an up-and-coming obesity biotech, AbbVie doubling down on psychedelics for mental health conditions and the fall of gene therapy’s darling shook and reshaped the biopharma sector in 2025, setting up excitement for the year ahead. Read on for 2025’s seven most impactful biopharma M&A deals. 1. The Pfizer/Novo/Metsera Saga, Obviously There could only be one story in the top spot, and it was the epic bidding war between Pfizer and Novo Nordisk over obesity startup Metsera. To make a long story short: Pfizer tried and repeatedly failed to develop a competitive obesity pipeline in-house. After several flunks earlier in 2025, the company looked to its business development team. Pfizer made a $4.9 billion offer for Metsera in September, to gain access to a long-acting GLP-1 and a long-acting amylin analogue. The deal seemed to be on the way to closing, until Novo offered an unsolicited $8.5 billion bid for the company a month later. Facing a different set of problems as the obesity space’s early leader, Novo was looking to rebuild its pipeline as rival Eli Lilly seemingly scored one win after another. A series of counteroffers, legal threats and FTC scrutiny followed, with Pfizer finally winning out for a price of about $9.2 billion for Metsera. With the dust now settled, Pfizer is back in the obesity business. The size of the obesity market, according to a Reports and Data analysis, is set to hit $27 billion yearly by as soon as 2028 and $150 billion by the early 2030s. The fight over Metsera seemed to indicate that Big Pharmas are still willing to go big in the obesity market. On the other hand, analysts wondered: Was it worth it? Obesity Is Metsera Worth the Fuss? Pfizer and Novo Nordisk seem to want Metsera bad. Analysts are wondering, though: Is the obesity biotech really worth this much effort? November 5, 2025 · 4 min read · Annalee Armstrong 2. BMS Spends $1.5B for Orbital as Others Retreat From Cell Therapy Over the course of 2025, there was a massive pullback from cell therapy, with Takeda and Novo Nordisk abandoning billions in long-term investments. But Bristol Myers Squibb doubled down. The Big Pharma plunked down $1.5 billion to get Orbital Therapeutics, snagging OTX-201, a circular RNA therapy that induces a patient’s own cells to make anti-CD19 CAR type constructs. The therapy is being tested to treat B cell–driven autoimmune disorders. The Orbital deal deepens BMS’ roots in cell therapy, adding to its approved anti-BCMA therpay Abecma , for relapsed or refractory multiple myeloma, and the CD19-directed Breyanzi for blood cancers. But the buy also told the industry that there is still potential in cell therapy if you know where to look. 3. Novo Deepens MASH Stature With $5.2B Akero Buy Metabolic dysfunction–associated steatohepatitis—MASH—is suddenly one of the buzziest sectors in the pharma industry again. Novo Nordisk paid $5.2 billion to get Akero Therapeutics in October, adding efruxifermin, which reduced liver fibrosis by 24% in a Phase IIb study that read out earlier this year . It was such a good result that it pushed Roche to go hunting for an anti-MASH molecule, spurring that company’s purchase of 89bio for $3.5 billion in September. The Akero buy only deepened Novo Nordisk’s presence in the MASH space, as its multi-blockbuster GLP-1 Wegovy received approval for the liver condition in August . The Roche and Novo deals marked a turning point for the MASH space, which Big Pharma had largely abandoned years ago after numerous failures. The small biopharma Madrigal Pharmaceuticals finally broke through with the 2024 approval of Rezdiffra in MASH, reigniting interest in the space. Psychedelics Psychedelics Space Enters New Era as AbbVie Dives In With AbbVie’s $1.2 billion acquisition of Gilgamesh Pharmaceuticals’ lead depression drug, the psychedelic therapeutics space has soundly rebounded from Lykos’ rejection last year. There are now seven programs in Phase III trials across the sector, with multiple companies vying for that first approval. September 22, 2025 · 6 min read · Heather McKenzie 4. AbbVie Goes Back to the Mental Health Well With Gilgamesh Buy AbbVie paid $1.2 billion to get just one asset from neurotech biotech Gilgamesh Pharmaceuticals in August . That gave them an entree at a table that Big Pharma has nibble at for a while: psychedelics. AbbVie gained bretisilocin, a fast-acting analogue of dimethyltryptamine (DMT) for major depressive disorder (MDD). The rest of Gilgamesh’s pipeline spun out into a separate company, Gilgamesh Pharma Inc., which carries on an existing AbbVie partnership. The Gilgamesh buy suggested that AbbVie was undeterred after a $9 billion quagmire in the form of Cerevel . AbbVie paid the princely sum to get the company and its schizophrenia asset emraclidine in 2023, which went on to flunk Phase II trials one year later . The Gilgamesh deal helped galvanize interest in psychedelics. AbbVie’s investment came at a time when most neuropsych-focused pharmas “have kept a distance,” from psychedelics according to Aaron Bartlone, CEO of the Canadian mental health biotech Cybin. The only other Big Pharmas in the psychedelics space right now are Johnson & Johnson, with its ketamine derivative Spravato, and Japanese giant Otsuka. The latter paid $59 million in 2023 to absorb Mindset, a Canadian psychedelics biotech. 5. Bluebird—Ahem, Genetix—Goes Private Bluebird was the standard bearer of gene therapy, until it wasn’t. Private equity outfits The Carlyle Group and SK Capital bought the biotech, which at one time had been worth north of $10 billion, for a scant $50 million in February . It was a precipitous fall for bluebird, which had more than $1 billion in cash the first quarter of 2021. That number fell to just $118.7 million by the third quarter of 2023 . Gene therapy is facing a “ cold winter ,” as promising science has not translated to good business, with sky-high costs and infrastructure issues hobbling the sector. Still, Carlyle and SK have options for turning bluebird’s assets into profits—including just selling the three approved gene therapies off, as PitchBook Senior Biotech Analyst Kazi Helal suggested to BioSpace in July. Those assets are Lyfgenia for sickle cell disease, Skysona for cerebral adrenoleukodystrophy and Zynteglo for beta thalassemia. Bluebird’s sale was the biggest indicator of a growing trend: the entry of private equity into the biotechnology space. In the last few years, PE firms like BlackStone have launched life sciences–focused funds, put billions of dollars into backing new ventures and even funded individual professors’ research. Bluebird renamed itself to Genetix in September , shedding a unique biopharma name adopted in 2010 and returning to its original moniker. Deals Bluebird Go-Private Deal Signals the ‘PE-ization of Pharma’ Why did two private equity firms with more than $460 billion under management want a little old gene therapy biotech called bluebird bio? We wanted to know. July 2, 2025 · 7 min read · Annalee Armstrong 6. Once Hot Sage Fades Away in Supernus Buy In late November 2024, Sage’s lead asset dalzanemdor flunked a Phase II trial for Huntington’s disease, the third such fail for the drug. It was just the capstone of a series of setbacks for Sage over the last few years; another asset, SAGE-324, flunked a Phase II study for essential tremor and was discontinued, and its Biogen-partnered postpartum depression drug Zurzuvae failed to get FDA approval in major depressive disorder. Maryland-based Supernus stepped in and scooped up Sage for $795 million in June . It was a “good end” for the company, according to analysts, and represented a much larger buyout than one put forward by long-time partner Biogen in January. Biogen offered $469 million to fold in its partner in Zurzuvae in January 2025 . Sage declined the offer with extreme prejudice, going so far as to sue Biogen. Along with Zurzuvae, Supernus absorbed Sage’s other approved drugs: the ADHD medication Qelbree; Onapgo, a wearable device for treating motor fluctuations associated with Parkinson’s disease; and Gocovri, for treating dyskinesia in Parkinson’s. Stifel analysts, writing at the time of the Supernus buy, said that it “feels like an unremarkable outcome for a company that was once one of the hottest stories” in treating central nervous system disorders. 7. BioNTech Ends CureVac Rivalry With a Pot of Money In 2022, BioNTech said in a lawsuit that it faced “threats of a groundless patent infringement suit” from a company that was “unable to bring to market any product to help in the fight against COVID-19.” Three years later, BioNTech bought that company, CureVac, for $1.25 billion, ending a winding legal drama that was still ongoing at the time of the deal. That purchase gave BioNTech a new mRNA-based therapy for the tough brain cancer glioblastoma. Despite both companies gaining fame for working on vaccines, the deal was motivated mostly by interest in cancer. Getting access to CureVac’s pipeline of cancer immunotherapies “marks the next milestone in the execution of [BioNTech’s] oncology strategy,” the company said in announcing the deal. Despite regulatory headwinds prevailing against mRNA-based therapies and vaccines in the U.S.—like the federal government canceling hundreds of millions of dollars in research dollars aimed at projects using the technology—BioNTech’s bid to swallow up its rival is a signal that, even as the company diversifies into other modalities like bispecifics , mRNA-based therapies as a platform are here to stay. .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to BioPharm Executive! 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亨廷顿病（Huntington's Disease, HD）作为一种由单基因缺陷引发的致命神经退行性疾病，长久以来被视为“不可逆转”的医学难题。然而，近年来随着对其致病机制的深入解析与靶向药物的快速推进，这一局面正被逐步打破——多款针对HTT基因、MutSβ复合物等核心靶点的候选药物已进入临床后期，部分甚至展现出“延缓疾病进展”的突破性疗效。但与此同时，基因疗法的监管门槛与商业化挑战也随之凸显，成为行业不得不面对的“成长痛”。 1. 从基因缺陷到神经元死亡：HD的致病逻辑 HD的“元凶”是位于4号染色体的HTT基因第1外显子中CAG三核苷酸重复序列的异常扩增——正常人群的CAG重复数通常在10-26次，而HD患者则超过36次，部分甚至高达120次。这种扩增会编码出一条异常延长的聚谷氨酰胺（polyQ）链，使原本负责囊泡运输、BDNF支持等生理功能的Huntingtin蛋白“变性”：它会错误折叠形成不可溶的聚集物，干扰细胞内转录调控，破坏轴突运输系统，抑制自噬清除机制，并阻断神经营养因子BDNF的产生与运输，最终导致纹状体中等棘突神经元（MSNs）与皮质神经元的选择性死亡。 更复杂的是，HD的病理进程并非单一通路驱动，而是涉及蛋白质稳态失调、神经营养缺失（BDNF/TrkB通路抑制）、自噬障碍（mTOR异常激活）、兴奋毒性（NMDA受体亚基GRIN2B过度激活引发钙超载）等多个环节的“协同作恶”。正如《Protein & Cell》2025年的研究指出，单一靶点的干预往往难以扭转疾病轨迹，这也为后续药物研发指明了“多通路协同”的方向。 2. 靶向核心通路：多款候选药物的“突围战” 在HD药物研发的赛道上，最受关注的是三类策略：直接降低突变HTT（mHTT）水平、靶向DNA修复机制、以及调节表观遗传。 1. 基因疗法：从“临床突破”到“监管考验” uniQure公司的AMT-130无疑是当前最受瞩目的基因疗法——它通过腺相关病毒（AAV）载体向脑部递送microRNA，特异性降低mHTT水平。2024年10月公布的Phase I/II期36个月中期数据显示，高剂量组患者的疾病进展速度减缓了75%（cUHDRS评分改善，P=0.003），脑脊液中的神经丝轻链（NfL，神经元损伤标志物）水平也低于基线，且安全性可控。这一结果曾让市场欢呼“HD首次被成功攻克”，uniQure的股价在2025年9月一度暴涨至三倍。 但好景不长，2025年11月FDA在pre-BLA会议上反馈，认为AMT-130的I/II期+外部对照数据不足以支撑加速审批，要求补充更多确证性数据。这一“变脸”直接导致uniQure股价单日暴跌55.7%，也让基因疗法的商业化路径蒙上阴影。 2. ASO疗法：精准打击的“潜力股” 与基因疗法的“一次性给药”不同，反义寡核苷酸（ASO）疗法通过定期输注抑制mHTT的表达。其中，Wave Life Sciences的WVE-003是首款“等位基因特异性”ASO——它仅针对突变的HTT基因，保留野生型HTT的功能（野生型HTT对神经元存活至关重要）。2025年公布的SELECT-HD早期数据显示，WVE-003可降低患者脑内40–50%的mHTT水平，且与尾状核萎缩减缓相关。而罗氏的Tominersen则采取“非等位基因特异性”策略，虽因高剂量组的风险/获益问题调整了临床试验方案，但仍在探索针对年轻、低疾病负担患者的可行性。 3. 表观遗传与DNA修复：新靶点的“破圈” 除了直接针对HTT基因，研究者还将目光投向了表观遗传调控与DNA修复机制。例如，组蛋白脱乙酰基酶3（HDAC3）作为表观遗传核心靶点，其选择性抑制剂在改善HD患者认知功能与神经保护方面展现出潜力——美国Sage Therapeutics的SAGE-718在II期临床试验中显示出相关疗效，推动市场对HDAC3靶向药物的关注度提升。而MutSβ复合物（MSH2+MSH3）作为DNA修复机器，却意外导致HD中CAG重复序列的扩增，抑制其活性有望阻止序列延长，成为新型疗法的关键靶点。 此外，药物递送技术的优化也在推进——氘代丁苯那嗪通过稳定血药浓度，在控制舞蹈症症状的同时，将镇静副作用减少了30%，成为对症治疗的重要进展。 3. 未来：从“突破”到“治愈”的距离 尽管HD药物研发取得了前所未有的进展，但要实现“治愈”仍需跨越多重障碍： 首先，单一靶点的干预往往难以扭转疾病的复杂病理网络，多通路协同的联合疗法将成为未来方向——例如，将mHTT降低疗法与BDNF-TrkB通路激活、自噬促进（mTOR抑制）相结合，可能更有效地保护神经元。 其次，基因疗法的监管要求日益严格，如何设计合理的临床试验（如对照人群的选择）、提供足够的有效性数据，成为企业必须解决的问题——uniQure的AMT-130就是典型案例。 最后，精准治疗的需求迫切——等位基因特异性ASO（如WVE-003）避免了抑制野生型HTT的风险，将为更多患者提供安全有效的治疗选择。 对于HD患者而言，这些进展意味着“希望”不再遥远——从“不可治”到“可延缓”，再到未来的“可治愈”，HD药物研发的每一步，都在向这一目标靠近。