Ociperlimab

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。在生物医药研发的征途上，每一款新药从实验室走向临床，都需历经重重考验，而三期临床试验作为通往市场的关键关卡，更是充满了不确定性。2025 年多家国际和国内药企在三期研发项目传来失利消息。1、阿斯利康：单抗Anselamimab7月16日，阿斯利康公布其治疗轻链型（AL）淀粉样变性的新药Anselamimab III期CARES研究结果。与安慰剂相比，Anselamimab在梅奥分期为IIIa和IIIb期的AL淀粉样变性患者中，未达到主要终点的统计学显著性。Anselamimab是一款在研的、潜在的首创抗淀粉样原纤维单克隆抗体，旨在通过减少或清除AL淀粉样变性患者组织和器官中的淀粉样蛋白沉积物来改善器官功能。在一个预设的患者亚组中，与安慰剂相比，Anselamimab在全因死亡时间和心血管住院频次方面显示出高度临床意义的改善。2、诺华：IL-17A单抗 Cosentyx7月初，诺华宣布其IL-17A单抗 Cosentyx（司库奇尤单抗）用于巨细胞动脉炎（GCA）成人患者的 III 期研究失败。Cosentyx为全球首款IL-17A  抗体，直接抑制白细胞介素 - 17A（IL-17A），这一细胞因子在多种免疫介导的炎症性疾病的炎症过程中扮演关键角色。自 2015 年上市以来，已在全球 100 多个国家获批，用于治疗多种免疫介导的炎症性疾病，例如中重度斑块状银屑病  、强直性脊柱炎、银屑病关节炎等。三期临床研究显示：与安慰剂相比，Cosentyx 在第 52 周并未在持续缓解方面展现出统计学意义上的显著改善。（相关阅读：诺华：60亿美元王牌药，III期研究失败）3、强生：眼病基因疗法bota-vec5月初，强生公布其眼病基因疗法botaretigene sparoparvovec(bota-vec)在3期临床试验未达主要终点。此次III期试验共招募了 95 名患者，其中58 名患者接受了单次低剂量或高剂量的 bota-vec 治疗，试验未能达到改善视觉导航能力的主要终点，但在试验的几个次要终点上显示出改善。bota-vec是一种基因疗法，利用一种腺相关病毒载体，将视网膜色素变性 GTP 酶调节因子 (RPGR) 基因的功能性拷贝输送到视网膜。强生在2023年以6500万美元的预付款，从MeiraGTx公司手中收购了bota-vec，并曾与该公司签署协议获取包括bota-vec在内的三种眼病基因疗法的授权。4、百济神州：TIGIT 抗体 Ociperlimab4月份，百济神州的 TIGIT 抗体 Ociperlimab（欧司珀利单抗，BGB - A1217）在肺癌治疗探索之路上也戛然而止。基于独立数据监查委员会的无效性分析，正在进行的 3 期临床试验 AdvanTIG - 302 难以达到总生存期的主要终点，这一决定让百济神州约 21 亿元的研发投入付诸东流。欧司珀利单抗作为一款针对 TIGIT 靶点的人源化 IgG1 变体单克隆抗体，此前百济神州对其与 PD - 1 抑制剂替雷利珠单抗联合治疗非小细胞肺癌（NSCLC）寄予厚望，然而现实却残酷地打破了幻想。5、罗氏：奥瑞利珠单抗4月份，罗氏宣布高剂量奥瑞利珠单抗治疗复发性多发性硬化症（RMS）的III期MUSETTE研究未达到主要终点。。III 期 MUSETTE 研究结果显示，在延缓 RMS 患者的残疾进展方面，1200mg 或 1800mg 的高剂量奥瑞利珠单抗效果不及已获批的 600mg 剂量。尽管高剂量组安全性良好，未出现新的安全性信号，但在关键的疗效指标上的失利，使得此次高剂量探索宣告失败。奥瑞利珠单抗是罗氏与渤健合作开发的一款靶向CD20阳性B细胞的人源化单克隆抗体。这类B细胞是一种特殊类型的免疫细胞，被认为是造成髓鞘和神经元轴突损伤的关键因素。2017年3月，奥瑞利珠单抗（商品名：Ocrevus）首次在美国获批上市，用于治疗复发性或原发性进行性多发性硬化症（MS）患者。2025年3月，奥瑞利珠单抗（商品名：罗可适）在中国获批上市。结语这些三期临床失败的案例，既是生物医药研发 “九死一生” 特性的真实写照，也为行业积累了宝贵的经验。它们提醒着药企在靶点选择、临床试验设计、剂量探索等环节需更加严谨与审慎。尽管失败令人惋惜，但每一次探索都在加深人类对疾病机制的理解，推动着研发思路的优化与技术平台的升级。参考资料：公开资料识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

“People went for Fc-competent [TIGITs] because it worked best in mice,” said Leerink Partners analyst Daina Graybosch, Ph.D. “They couldn\'t help themselves.\"\n Once hailed as the future of immuno-oncology, it’s been a tough few months for any remaining fans of anti-TIGIT antibodies.In April, BeOne Medicines, formerly known as BeiGene, announced it was scrapping ociperlimab over a disappointing phase 3 outlook two years after Novartis handed back the asset. Specifically, the study’s independent data monitoring committee deemed the trial unlikely to show that a combination of ociperlimab and BeOne’s own PD-1 inhibitor Tevimbra would beat Keytruda in patients with PD-L1-high non-small cell lung cancer (NSCLC).The following month brought more tough times for TIGITs, as GSK halted development of its own candidate belrestotug after deciding the iTeos Therapeutics-partnered drug in combination with anti-PD-1 inhibitor Jemperli wouldn’t score a phase 2 win in a similar NSCLC population.Even executives at Roche, whose tiragolumab appeared to buck the trend with a caveated phase 3 win in esophageal cancer in 2024, reaffirmed to Fierce Biotech earlier this year that “we stopped all of the tiragolumab trials that we could stop, and those that couldn\'t be stopped are just running out.”With Big Pharma having pumped $6 billion into this modality, what went so wrong for TIGITs?Daina Graybosch, Ph.D., a senior research analyst at Leerink Partners who covers immuno-oncology, traces the problems back to the exuberant reaction to Roche’s impressive phase 2 tiragolumab data that read out across 2020 and 2021. The Cityscape trial demonstrated that the TIGIT drug in combination with Roche’s own PD-L1 blocker Tecentriq shrank tumors in 31% of patients with metastatic lung cancer—twice as many patients as Tecentriq alone.“That\'s probably the biggest point where the field went wrong, in that they looked at this massive benefit in the small phase 2, and everybody ran after it in a parallel and broad way,” Graybosch told Fierce in an interview.“We had randomized phase 2 data from Roche, from Arcus-Gilead, from iTeos-GSK, and they all consistently showed benefit in response rate and in [progression-free survival],” she added.“I think the challenge ultimately was: How much benefit is there really? Is it enough benefit to be clinically meaningful? And are we developing the drugs in the right way, in the right format, to optimize and bring that benefit to patients?”The industry’s “overenthusiasm” for the potential of TIGITs led to a “simplistic approach” to how other companies planned to develop their own candidates, according to Graybosch.If pharmas had anticipated a “more realistic demonstration of benefit,” as seen in the failed Skyscraper-01 phase 3 study in NSCLC, “I think everybody would have developed [TIGITs] differently,” she suggested.Companies swimming in the TIGIT space have broadly fallen into two camps. Roche’s tiragolumab, along with Merck & Co.’s vibostolimab, GSK and iTeos’ EOS-448, and BeOne’s ociperlimab, are all Fc-enabled. These antibodies retain a fully functional Fc region, meaning they can bind to Fc receptors found on the cell surface and contribute to the protective antitumor functions of the immune system.The theory behind Fc-enabled anti-TIGIT antibodies is that they have enhanced tumor-killing effects. However, the risk is that they could possibly also eliminate certain regulatory T cells and therefore lead to unwanted immune responses.In fact, side effects did cast a shadow over some of the Fc-enabled TIGIT trials, with Merck halting a phase 3 trial of vibostolimab due to a higher than expected rate of discontinuations blamed on “immune-mediated adverse experiences.”“Toxicity that may lead patients to discontinue I think ended up being a contributing factor across the Fc-enabled TIGITs that are all now dead,” Graybosch said.The last TIGITs still standing—Arcus Biosciences and Gilead’s domvanalimab, as well as AstraZeneca’s TIGIT/PD-1 bispecific antibody rilvegostomig—have mutated out the Fc function. This should mean they are less toxic for patients.“People went for Fc-competent because it worked best in mice,” Graybosch explained. “They couldn\'t help themselves, even though they knew there was some risk of depleting T effector cells that are actually what you need to fight your tumor.” Focusing on \'modest benefit\'So, what would a more measured approach to the TIGIT gold rush have meant in practice?“I think you ultimately do what Astra is doing,” said Graybosch, referring to AstraZeneca’s ongoing phase 3 trials of its bispecific rilvegostomig in a range of phase 3 studies for NSCLC or stomach cancer, including in combination with its Daiichi Sankyo-partnered antibody-drug conjugates Enhertu or Datroway.“Astra is recognizing the modest benefit,” she explained. “Their bispecific is very safe because it\'s Fc silent. And in some ways, Astra can\'t lose because [rilvegostomig] doesn\'t need to work that much for a lot of their trials to be successful.”AstraZeneca’s Puja Sapra, Ph.D., senior vice president for biologics engineering and oncology target discovery, was also upbeat about rilvegostomig’s prospects when she spoke to Fierce back in April. She pointed to the fact that engineering the bispecific to reduce Fc effector functionality should reduce unwanted side effects, while blocking both PD-1 and TIGIT at the same time “should hopefully help us increase the response rate and durability.”“At least in preclinical studies, we see that a bispecific molecule has better responses than a combination of both agents alone,” Sapra said at the time. “The molecule is doing very well in the clinic so far, so we continue to believe in this molecule.”Gilead is also staying loyal to its TIGIT candidate, which is being evaluated in phase 3 trials for first-line NSCLC as well as for locally advanced unresectable or metastatic gastric, gastroesophageal junction and esophageal adenocarcinoma.The pharma’s chief medical officer Dietmar Berger, M.D., Ph.D., told Fierce earlier this month that the Arcus-partnered domvanalimab still has a chance, pointing to its Fc-silent character.“We believe there is differentiation but, of course, we need to see how those studies read out,” Berger said. “Any additional activities around that will be based on what we see in those studies.”With AstraZeneca and Gilead still holding a candle for their Fc-silent candidates, Leerink’s Graybosch doesn’t think “it\'s fair to completely write off TIGIT.”“But if you ask 99% of average investors, generalists or specialists and [key opinion leaders], I think they’ll tell you it\'s dead,” she added.Angus Liu contributed to this reporting.