Deupirfenidone

A clinical study testing a Pliant Therapeutics drug once considered a promising prospect for treating a fatal lung disorder is now on pause at the recommendation of independent outside observers. Pliant disclosed few details and said it is still reviewing data, but the clock is ticking for the company to figure out next steps for the drug and the patients in the clinical trial. The pause on the Phase 2b test is voluntary, Pliant said in its announcement after Friday’s market close. No new idiopathic pulmonary fibrosis (IPF) patients will be enrolled during this pause. Currently enrolled participants will remain in the study but will not be dosed with the experimental drug, bexotegrast. The study will remain blinded to preserve integrity of the data. Pliant said it has informed clinical trial investigators and is in the process of informing regulators. IPF is a progressive disorder in which scar tissue builds up in the lungs, leading to worsening lung function that eventually becomes fatal. The few available treatments slow IPF’s progression but do not modify the course of the disease. Bexotegrast is a small molecule designed to inhibit TGF-beta, a signaling protein that leads to the production of collagen that impairs lung function. presented by Artificial Intelligence What Keeps Healthcare CIOs Up at Night: Balancing Technology Investments with Consumer Expectations When it comes to managing inbound phone calls, underperformance has devastating cost implications. By Stephanie Baum Phase 2a results reported last year showed that after 12 weeks, the Pliant drug led to a reduction in collagen while the placebo group showed an increase in collagen. Pliant also said the reduction in collagen correlated with improvement in lung function. No safety signals were reported in this study. The trial that’s now paused is the Phase 2b portion of a Phase 2b/3 study designed to evaluate treatment with bexotegrast for 52 weeks. This placebo-controlled test was expected to post preliminary data in 2026. Over the course of a clinical trial, a data safety monitoring board, an independent body comprised of outside experts, evaluates safety and efficacy data at regular intervals. In Pliant’s announcement, the company said the board’s recommendation of a trial pause followed a prespecified data review. To Leerink Partners analyst Faisal Khurshid, the voluntary pause and the continued blinding of the trial could mean the trial did not trigger pre-specified stopping criteria for safety or efficacy. But it also means the board saw something concerning enough to recommend pausing all patient dosing, he said in a note sent to investors. Since the study did not meet pre-specified stopping criteria, Pliant may not be required to unblind the study, Khurshid said. Unblinding the study would mean all data integrity would be lost. Khurshid added that the board may be taking a conservative stance of not providing the exact reasoning to Pliant. That leaves the company to choose whether to unblind the data to learn the reason. Losing data integrity means Pliant would need to start over, assuming there is a path forward for the drug. The other choice is to maintain the blind and try to work with the board in a way that does not compromise data integrity. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech “In theory we think the resolution could be something like stopping one of the dose levels, excluding certain patient types, or prohibiting certain background therapies,” Khurshid said. “Again, this is all speculation. It will be important this occurs quickly as many patients were midway through a 52-week dosing period and the handling of the dosing suspension may become an issue the longer this goes.” If the study is salvageable, moving forward would likely require a major amendment to the clinical trial protocol, Khurshid said. He added that even in an optimistic scenario, Pliant may need to restart a pivotal clinical trial program, which would mean a multi-year delay. Investors did not welcome any of these options. Shares of Pliant opened Monday at $3.02, down more than 61% from Friday’s closing price. Pliant is one of several companies working to develop new drugs for IPF. Boehringer Ingelheim is at the front with nerandomilast, a small molecule designed to inhibit phosphodiesterase 4B (PDE4B), an enzyme whose roles include regulating inflammation. After announcing this drug met the main goal of its pivotal IPF studies last September, the company said it planned to seek approvals from the FDA and other regulators around the world. Nerandomilast is also in development for a different respiratory condition, interstitial lung disease. On Monday, Boehringer reported the drug met the main goal of a Phase 3 study in this indication. Full safety and efficacy data will be released in the second quarter of this year. Meanwhile, PureTech Health is developing deupirfenidone (formerly LYT-100), which employs chemical modifications to improve the tolerability of the old IPF drug pirfenidone. In December, PureTech reported its drug met key goals of a Phase 2b study with results showing improvement in measures of lung function. Another company, Insilico Medicine, is in mid-stage clinical development with ISM001-055, a small molecule inhibitor of an enzyme called TNIK. This IPF drug candidate was discovered with Insilico’s artificial intelligence platform technology. Photo by Flickr user Dominick Guzzo via a Creative Commons license

▎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