Trontinemab

一款曾被寄予厚望的国产创新药，在争议中上市，在质疑中停产，如今又因一笔超过14亿元的收购重回聚光灯下。 2025年12月15日，复星医药发布公告，宣布控股子公司复星医药产业拟出资 14.12亿元 控股投资绿谷医药，收购完成后，绿谷医药将成为复星医药控股子公司。 这笔交易的焦点是绿谷医药的核心产品——甘露特钠胶囊（代号GV-971，商品名“九期一”）。这款曾被誉为“国货之光”的阿尔茨海默病治疗药物，在过去六年里经历了从辉煌到停产的过山车式旅程。 01 收购细节，复星医药的精准布局 复星医药此次收购采取多步骤交易结构，体现其谨慎且精准的战略布局。根据公告，本次收购包括三部分： 首先是 转让环节 ，复星医药产业出资1.43亿元受让绿谷医药2015万元注册资本。其次是 认购新增注册资本 ，复星医药产业出资12.69亿元认缴绿谷医药约2.01亿元新增注册资本。 最为巧妙的是 阶段性转让 设计：为处理存续股权激励计划中的退股问题，由绿谷医药现有股东以象征性对价向复星医药产业与创始人共同设立的SPV转让部分股权。 交易完成后，复星医药将合计持有绿谷医药 53%股权 ，绿谷医药将纳入复星医药合并报表范围。若后续转让完成，复星医药最终将持有51%股权，保持绝对控股地位。 复星医药CEO兼总裁刘毅表示：“本次对绿谷医药的投资，是复星医药加码中枢神经系统诊疗领域布局的重要落子。阿尔茨海默病是应对人口老龄化国家战略的重点疾病之一。” 02 “九期一”的起伏，从辉煌到停产 甘露特钠胶囊的命运充满戏剧性。2019年11月，国家药监局有条件批准GV-971上市，用于治疗轻度至中度阿尔茨海默病，改善患者认知功能。那时，它被誉为全球首个靶向脑肠轴的阿尔茨海默病治疗新药，打破了该领域 17年无新药上市 的困局。 这款药物源自海洋褐藻提取物，是中国自主研发并拥有自主知识产权的创新药，获得国家重大新药创制科技重大专项支持。从研发到上市，甘露特钠胶囊经历了长达22年的漫长历程。 市场对GV-971的回应一度非常热烈。纳入医保后，2022年其在医院终端市场的销售额达1.70亿元，同比激增649.43%；到2024年的销售额已突破 4亿元 ，持续保持高速增长。 然而好景不长。由于“有条件批准”的监管要求，绿谷制药需要继续完善药理机制研究和长期安全性数据。根据法规，药品注册证书有效期五年，需在届满前六个月申请再注册。 2024年11月，甘露特钠胶囊的药品注册批件到期，因未能完成上市后确证性临床研究要求，未获得再注册批准。从那时起，该药品 未开展商业化生产 。 03 附条件批准，机遇与风险并存 “九期一”的审批困境折射出中国药品附条件批准政策的双刃剑效应。2019年获批时，国家药监局要求绿谷继续进行临床试验等方面研究，补充相关所需数据。 按规定，药品需在 4年内 换成“完全批准”的批文，否则可能面临退市。绿谷虽在2024年5月启动再注册申报，但未能如期完成确证性临床试验。 2025年8月，国家药监局政务服务门户信息显示，甘露特钠胶囊出现在“药品通知件送达信息”中，而非“药品批准证明文件送达信息”，标志着其再注册申请未获批准。 阿尔茨海默病药物研发的困境是全球性的。该领域失败率高达 99.6% ，远超癌症的81%，被称为“研发黑洞”。病理机制未明、血脑屏障限制、患者异质性高以及临床试验周期长都是主要挑战。 04 争议不断，机制与数据的双重质疑 “九期一”从诞生之日起就伴随着科学界的强烈质疑。与全球主流的针对β-淀粉样蛋白或Tau蛋白的研发路径不同，GV-971提出了独特的“脑肠轴”理论。 该理论认为，肠道菌群失调是诱发阿尔茨海默病神经炎症的关键环节。GV-971通过重塑肠道菌群平衡，减少有害代谢产物，抑制外周炎症细胞向大脑浸润，从而减轻神经炎症，改善认知功能。 然而，这一颠覆性理论面临严格审视。最激烈的争论发生在首都医科大学前校长饶毅与“九期一”发明人耿美玉之间。饶毅曾公开质疑：“这篇文章不造假，是不可能的。”这场争论最终诉诸法律，2023年，上海市第一中级人民法院二审驳回耿美玉上诉，维持原判。 临床试验数据同样备受质疑。GV-971的国内III期临床试验纳入818名患者，进行了为期36周的治疗。结果显示，治疗组较安慰剂组认知功能改善2.54分。但专家指出，这一试验规模相比国际标准 相对较小 ，且2.54分的改善幅度被一些专家认为“好得不真实”。 阿尔茨海默病已成为全球公共卫生领域的重大挑战。《柳叶刀》2024年报告显示，预计到2050年，全球痴呆症患者人数将在2019年的基础上翻2倍，达到1.53亿。而阿尔茨海默病正是痴呆症的主要类型。 05 复星的考量，战略布局与风险把控 复星医药此次收购背后，是对阿尔茨海默病治疗市场前景的精准判断。复星医药在中枢神经系统领域已有布局，此前曾许可引进用于延缓阿尔茨海默病疾病进程的小分子口服药物AR1001。收购后，复星医药或许将接力承接源自中国的科学探索，全力支持推进甘露特钠胶囊的 上市后确证性临床研究 ，以期尽快实现获批。 此外，复星医药正在加强其中枢神经系统领域布局。2025年12月12日，复星医药刚刚携手深圳理工大学共建AI驱动医药研发公共服务平台，项目获深圳市战略性新兴产业资助。 06 阿尔茨海默病治疗的新希望 在全球范围内，阿尔茨海默病治疗研究正在迎来新的突破。2025年以来，多款新机制药物取得重要进展。 小分子药物领域， Galimedix Therapeutics公司的GAL-101一期临床试验顺利完成，该产品能够有效穿越血脑屏障，通过靶向错误折叠Aβ单体，阻止有毒Aβ寡聚体和原纤维的形成。 抗体药物 也有新突破。罗氏公司在研抗体trontinemab运用 大脑穿梭技术 ，可持续实现快速且显著的淀粉样蛋白斑块清除：91%的受试者在淀粉样蛋白PET评估中转为阴性。 中国科研人员也在积极探索新路径。中国科学院院士谭蔚泓与团队开发出基于核酸适体的单核细胞疗法，能够高效清除阿尔茨海默病脑内的致病性蛋白Tau，为神经退行性疾病提供了新的治疗策略。 这些创新研究为阿尔茨海默病治疗带来全新希望，也为复星医药重新开发“九期一”提供了有利的科学环境。 阿尔茨海默病药物研发领域如同一个“黑洞”，失败率高达99.6%。绿谷医药的“九期一”曾是这个黑洞中的一缕亮光，如今复星医药试图重新点燃这束光。 复星医药面临的挑战不容小觑。除了要完成确证性临床试验，还需重塑医生和患者对“九期一”的信心。然而，全球超过 200项 在研阿尔茨海默病管线正在临床研究阶段，科学探索的脚步从未停止。 对于中国数百万阿尔茨海默病患者而言，他们期待的不仅是一款价格可及的药物，更是一个经得起科学检验的有效治疗方案。复星医药的14亿投资，最终能否换来千万患者的希望，一切都有待时间与数据的检验。

iStock, beast01 In the midst of regulatory and political upheaval, biopharma’s R&D engine kept running, churning out highs and lows in equal parts. Here are some of this year’s most glorious clinical trial victories. 2025 continued a difficult stretch for biopharma, as funding continued to crawl for much of the year before showing signs of life in the fourth quarter—and several companies experienced regulatory whiplash as the FDA seemingly reversed positions it had only recently communicated. Add to this an FDA that is hemorrhaging institutional knowledge and a health secretary consistently communicating scientifically questionable positions and it’s been a rollercoaster of a year. Still, the industry perseveres. Drugmakers continued to advance their investigational products, braving the turbulent drug development waters in the hopes of bringing an innovative therapy to the market. And while this effort often ends in failure — 90% of investigational drugs flunk out in clinical trials—several companies, including uniQure, Roche and Novo Nordisk clinched key clinical victories in challenging and lucrative indications. In this piece, BioSpace looks back at some of the biggest trial successes this year, reviewing not only the data but also their broader impact on the company and industry as a whole. UniQure Scores Historic Huntington’s Win, Despite FDA Pushback On Sept. 24, uniQure announced that its gene therapy slowed the progression of Huntington’s disease by 75% at the three-year mark. Aside from disease progression, AMT-130 also hit key secondary endpoints, improving functional capacity and lowering the concentrations of a key disease biomarker versus outside comparators. The data exceeded analyst expectations and could pave the way for the first genetic treatment for the devastating neurodegenerative disorder—barring any regulatory roadblocks. But that’s exactly what uniQure ran into in just five weeks later. Last month, despite having aligned with the FDA on the protocols and analytical models used in the pivotal study, uniQure revealed that the regulator “no longer agrees” that Phase I/II data for AMT-130 is “adequate to provide the primary evidence in support of a [biologics license application] submission.” UniQure had been planning to BLA early in 2026, but following the FDA’s seeming reversal, the timeline for submission is now “unclear,” the biotech said in November . In a Nov. 3 note, Stifel analysts called the FDA’s about-face “a shock,” adding that the decision could have far-reaching stock implications not just for uniQure but also for “other development stage companies in the gene therapy space.” Elsewhere in the Huntington’s space, PTC therapeutics reported positive Huntington’s data in May from a Phase II study of its small-molecule drug PTC518, though analyst reaction has been mixed. While the drug elicited a 23% reduction in the huntingtin protein, William Blair in a May 5 note said that a link between the biomarker and functional remains to be proven. The analysts also flagged the lack of functional benefit in patients with later-stage disease. Metsera’s Weight-Loss Win-Streak Sparks Big Pharma Tug-of-War Rising obesity star Metsera captured the industry’s attention in September last year when it announced that its GLP-1 injectable MET-097i achieved 7.5% weight-loss at 36 days in an early study. This year, the New York biotech proved that its success wasn’t a fluke—and secured a nearly $10 billion buyout for its efforts. Metsera kicked off 2025 with more data for MET-097i, this time from a Phase IIa trial involving 120 patients with overweight or obesity, but without type 2 diabetes. After 12 weekly doses, patients on the GLP-1 injection dropped 11.3% of their body weight versus placebo. Some patients lost as much as 20% of their weight, the biotech said at the time, adding that it did not observe any plateauing effect. Metsera followed this up with another mid-stage data drop in late September, touting a 14.1% placebo-adjusted weight reduction with MET-097i at 28 weeks—findings that Leerink Partners in a Sept. 30 note called “very encouraging.” Eli Lilly’s blockbuster medicine, tirzepatide,“achieved about a 13% placebo-adjusted weight-loss” at a similar length of follow-up, the analysts noted. Late-stage development for MET-097i is slated for late-stage development within the year. Beyond MET-097i, Metsera’s ultra-long-acting amylin injectable MET-233i induced 8.4% weight-loss versus placebo at 36 days in a Phase I study that read out in June. Some patients on MET-233i saw a 10.2% reduction in body weight. These results were enough to ignite one of the most high-pro not messiest—biopharma bidding war —in recent history. Pfizer in mid-September announced that it would acquire the biotech for $4.9 billion , setting the pharma up for an obesity comeback after suffering several failed assets. A month later, however, Novo Nordisk submitted a rival bid worth $8.5 billion . This intrusion—which Metsera seemed to welcome, calling the offer “ superior ” to Pfizer’s—set off a very public back-and-forth between the companies, involving lawsuits from the New York pharma. Ultimately, Pfizer prevailed, upping its offer to $9.2 billion to definitively win Metsera’s hand in corporate marriage. Novo Bounces Back With Phase II Amycretin Win Despite losing out on Metsera , Novo Nordisk nevertheless notched a crucial victory last month as its oral amylin candidate amycretin demonstrated a “competitive” pro a mid-stage diabetes study. In a Phase II trial of nearly 450 patients with type 2 diabetes, Novo’s amylin pill led to 7.6% weight loss at 36 weeks as compared with placebo. The subcutaneous injection, meanwhile, cut 11.9% off patients’ body weight. BMO Capital Markets called this efficacy profile “competitive,” noting amycretin’s “potentially differentiated profile” in the increasingly crowded space of oral obesity treatments. “Importantly, no weight loss plateau was observed in either administration route, suggesting the potential for additional weight loss at longer time points,” BMO added. Amycretin also elicited a 1.5% decrease in blood glucose levels, as represented by HbA1c at the same time point. A subcutaneous formulation of the drug, meanwhile, elicited a 1.8% HbA1c drop. Amycretin’s Phase II win helps deliver some vindication for Novo’s obesity franchise, which in recent months has been struggling both clinically and commercially. Its blockbuster drug Wegovy, for instance, has been ceding market share to Lilly’s Zepbound, despite breeching the market first. Novo has blamed compounders for Wegovy’s shaky commercial footing, but analysts are skeptical. During the company’s first quarter earnings call in May, Peter Verdult of BNP Paribas floated a difficult theory: “Is it really only about the compounders or do we have to consider your nearest branded competitor doing a better job?” The Danish pharma has also been struggling clinically. In December last year, its next-generation weight-loss therapy CagriSema delivered disappointing outcomes . The asset, which combines semaglutide with amylin analog cagrilintide, met its primary endpoint in the Phase III REDEFINE 1 study, but its 22.7% weight-reduction fell short of investor expectations —which Novo itself set—erasing some $72 billion off the company’s market cap. Meanwhile, a day before the amycretin readout last month, Novo reported that semaglutide was unable to significantly slow Alzheimer’s disease progression in the Phase III EVOKE and EVOKE+ studies. While expectations for this program had not been high, the data drop still knocked some 10% off Novo’s shares in its aftermath. BMS/BioNTech Eye PD-1/VEGF Leadership With Geographically Consistent Data One of the most closely watched—not to mention most clinically promising—trends in cancer today is the rise of PD-1/VEGF inhibition. Achieved through the use of bispecific antibodies that bind and block both receptors, the PD-1/VEGF approach rose to prominence in September last year, when Summit Therapeutics and its Chinese partner Akeso claimed victory over Merck’s mega-blockbuster Keytruda. In a late-stage non-small cell lung cancer trial, the partners’ ivonescimab achieved nearly 50% better progression-free survival than the cornerstone cancer therapy. BioNTech jumped into the space a few months later, acquiring Biotheus for up to $950 million and gaining access to its PD-1/VEGF bispecific BNT327. This investment has paid off nicely for BioNTech. In September, the company reported data from a global Phase II trial showing that BNT327, which has since been named pumitamig, given alongside standard chemotherapy, elicited a 76.3% overall response rate (ORR) in patients with extensive-stage small cell lung cancer. Disease control rate hit 100%. In a Sept. 8 note, analysts at Truist Securities said that these data were “very reassuring” since they “confirmed the treatment effect seen in China.” Analysts were referring to a Phase II readout from pumitamig in March, which demonstrated a confirmed ORR of 85.4% in Chinese patients . Disease control rate in this trial was 97.9%. Encouraged by these data, BioNTech has taken pumitamig into late-stage development in the same indication, for which it is running the Phase III ROSETTA-LUNG-01 trial . To establish the antibody’s efficacy across different patient populations, the study is enrolling across different geographies, including the U.S., China, Australia and Korea. ROSETTA-LUNG-01 is set to complete in March 2029. Aside from performing well in the clinic, pumitamig has also helped BioNTech garner hefty support from the industry’s heavy hitters. In June, Bristol Myers Squibb put more than $11 billion on the line—including $3.5 billion upfront and up to $7.6 billion in milestones—for the right to co-develop and co-commercialize the asset. Roche Makes Alzheimer’s Comeback With Mid-Stage Win Neuroscience has classically been a challenging space for biopharma, and 2025 was no different. With many companies posting clinical failures in this space—Roche secured a key victory this year in one of the most intractable indications: Alzheimer’s disease. At the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) meeting earlier this month, the pharma presented data from its ongoing Phase I/II Brainshuttle AD study demonstrating that 92% of patients treated with its next-gen anti-amyloid antibody trontinemab achieved amyloid levels lower than 24-centiloid, a key threshold determining the presence of amyloid plaques on a PET scan. Trontinemab also showed a potential benefit on the tau accumulation in the brain. As for safety, amyloid-related imaging abnormalities suggestive of brain swelling or bleeding occurred in fewer than 5% of treated patients. These findings echo an earlier data drop during the 2025 Alzheimer’s Association International Conference (AAIC) in July. In a presentation at the meeting, Roche reported that 91% of trontinemab-treated patients tested negative on a PET scan for amyloid in the brain, while 72% achieved “deep clearance” of amyloid clumps. Trontinemab represents an Alzheimer’s comeback for Roche. In late 2022, Roche’s gantenerumab, likewise an anti-amyloid antibody failed two Phase III studies, forcing the pharma to pull the plug on the program. Meanwhile, at-home administration of anti-amyloid drug Leqembi is becoming a reality, companies like Eisai continue to advance candidates against tau, and 30-plus trials are underway against what Alzheimer’s Drug Discovery Foundation Co-founder and Chief Science Officer Howard Fillit recently told BioSpace earlier this month is the industry’s hottest target: inflammation. “Forty years of research is finally paying off,” he said. Alzheimer’s disease Eisai Still Confident in Anti-Tau Asset as J&J Becomes Latest Victim in Spiraling Space Days after Johnson & Johnson’s posdinemab failed to slow clinical decline in patients with Alzheimer’s disease, Eisai Chief Clinical Officer Lynn Kramer expressed unwavering conviction in his company’s own anti-tau asset, while others suggest the Alzheimer’s field is heading in a completely different direction. December 5, 2025 · 4 min read · Heather McKenzie