Pirfenidone

▎药明康德内容团队编辑 今日，PureTech Health公布了ELEVATE IPF临床2b试验的积极结果。分析显示，其在研小分子deupirfenidone（LYT-100）达成主要终点，能够显著改善特发性肺纤维化（IPF）患者的肺功能。 ELEVATE IPF是一项针对IPF患者的2b期随机、双盲的剂量探索试验，评估了每日三次（TID）两种剂量的deupirfenidone与获批药物pirfenidone（801 mg）以及安慰剂相比，使用26周后的疗效和安全性。 分析显示，试验成功达到主要终点。试验26周时，每日三次825 mg deupirfenidone显著减少患者的用力肺活量（FVC）下降幅度，与安慰剂相比表现出统计学显著差异（-21.5 mL vs. -112.5 mL，p=0.02），显示出80.9%的显著治疗效果。此外，试验还展现显著的剂量依赖性疗效。一般而言，健康60岁以上人群在6个月内的FVC自然下降幅度约为-15.0 mL 至-25.0 mL。而每日三次活性对照药物相较于安慰剂的治疗效果则为54.1%（-51.6 mL vs. -112.5 mL），与该药物此前的临床试验结果一致。 ▲ELEVATE IPF试验疗效结果摘要（图片来源：参考资料[1]） 试验也达成关键次要终点，表明deupirfenidone治疗在减缓FVC百分比预测值（FVCpp）下降方面优于安慰剂组。FVCpp是另一种肺功能的衡量指标，除了FVC本身外，还综合考虑了患者的年龄、性别、身高和种族等关键特征，从而在患者层面进行标准化。Deupirfenidone在这一终点上也表现出统计学显著差异（-0.43 vs. -3.43，p=0.01），进一步验证了其治疗效果。 此外，试验结果显示，两种剂量的deupirfenidone耐受性良好，安全性特征与既往研究一致。 Deupirfenidone是氘代pirfenidone，而pirfenidone是与nintedanib并列用于治疗IPF的两种标准疗法之一。通过氘代修饰，deupirfenidone在体内代谢速度更慢，从而可能延长药物作用时间并改善疗效。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] PureTech’s Deupirfenidone (LYT-100) Slowed Lung Function Decline in People with Idiopathic Pulmonary Fibrosis (IPF) as Measured by Forced Vital Capacity (FVC), Achieving the Primary and Key Secondary Endpoints in the ELEVATE IPF Phase 2b Trial. Retrieved December 16, 2024 from https://www.businesswire.com/news/home/20241215811061/en/PureTech%E2%80%99s-Deupirfenidone-LYT-100-Slowed-Lung-Function-Decline-in-People-with-Idiopathic-Pulmonary-Fibrosis-IPF-as-Measured-by-Forced-Vital-Capacity-FVC-Achieving-the-Primary-and-Key-Secondary-Endpoints-in-the-ELEVATE-IPF-Phase-2b-Trial 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

PureTech Health unveiled positive Phase 2b data on Monday for its idiopathic pulmonary fibrosis drug, which showed it can reduce lung function decline in patients. The drug hit the trial’s primary and secondary endpoints, with deupirfenidone showing superiority to placebo in slowing the rate of lung function decline in people with IPF as measured by forced vital capacity — defined as the amount of air a person can exhale after taking a breath in — at 26 weeks. Patients taking the investigational drug at 825 mg three times a day saw an 80.9% treatment effect. In contrast, patients taking 801 mg of pirfenidone, a standard-of-care for IPF, saw a 54.1% effect. In a secondary endpoint, there was a 99.6% probability that the pooled deupirfenidone arms of the trial were superior to placebo in slowing the rate of lung function decline when using a Bayesian analysis. Executives on a Monday investor call said that the results supported moving into a Phase 3 trial. CEO Bharatt Chowrira added on the call that based on the data, only one more trial may be necessary before the company seeks approval. PureTech’s stock $PRTC on the Nasdaq was up nearly 10% on Monday. Deupirfenidone, a deuterated form of pirfenidone, is an oral treatment that works by inhibiting IL-6, TNF-α and transforming growth factor beta, according to the National Cancer Institute. As for safety, the most common adverse events included gastrointestinal issues like nausea and dyspepsia, and the only “key” gastrointestinal adverse event seen was abdominal pain, with 14.1% of patients on the drug experiencing the issue. “We’ve looked into it,” PureTech’s VP of medical affairs Camilla Graham told investors. “There’s no signal, no cause for any concern, and we’re continuing to dig into all of these numbers.” There were discontinuations, with 187 out of 257 patients completing the trial: 42 out of 65 patients in the deupirfenidone 550 mg arm and 50 out of 64 patients in the 825 mg arm. Of the patients who completed the trial, 170 enrolled in the open-label extension portion of the trial. In response to a question about discontinuations from Endpoints News , a representative for the company said they “have just received these data and our primary focus has been assessing efficacy and the key GI adverse events,” adding that “there is nothing in the data to give us cause for concern.”