Nintedanib esylate

近日，《新英格兰医学杂志》（NEJM）发表了一项针对特发性肺纤维化患者的3期临床试验结果，表明肺纤维化创新疗法nerandomilast（BI 1015550）可显著减缓患者肺功能下降，治疗第52周时，相较于安慰剂组，nerandomilast减少44.9~68.8 ml的用力肺活量（FVC，指深吸气至肺总量，做最大力量、最快速度的呼气所呼出的最大气体容积）。这一研究表明，nerandomilast为特发性肺纤维化患者提供了潜在的治疗选择，对已接受尼达尼布或吡非尼酮治疗的患者也同样有效。截图来源：NEJM特发性肺纤维化，俗称“蜂窝肺”，是一种病因未明的慢性、进行性、纤维化性间质性肺炎，以呼吸困难进行性加重和肺功能进行性恶化为主要临床特征，现有治疗手段比较有限，患者预后较差。Nerandomilast是口服磷酸二酯酶4B（PDE4B）抑制剂，正被开发作为特发性肺纤维化和进展性肺纤维化的潜在治疗药物。Nerandomilast已获得美国FDA突破性疗法认定，用于治疗特发性肺纤维化。此前一项2期试验已证实，nerandomilast治疗12周，即可稳定患者肺功能，而本次3期研究结果则进一步验证了更长期的疗效。这项双盲试验纳入了1177例特发性肺纤维化患者，其中77.7%患者在入组时已接受尼达尼布或吡非尼酮治疗。患者被随机分为3组，分别接受每日两次、18 mg或9 mg剂量的nerandomilast或安慰剂治疗。研究主要终点是治疗第52周时FVC较基线的变化绝对值。结果显示，治疗第52周时，18 mg nerandomilast组、9 mg nerandomilast组和安慰剂组的FVC较基线分别平均下降114.7 ml、138.6 ml和183.5 ml。相较于安慰剂，18 mg nerandomilast组和9 mg nerandomilast组FVC下降分别显著减少68.8 ml（P＜0.001）和44.9 ml（P=0.02）。安全性方面，腹泻是最常见的不良反应，其中18 mg nerandomilast组发生率为41.3%，9 mg nerandomilast组为31.1%，而安慰剂组为16.0%。3组严重不良事件发生率相对均衡。总之，这项3期试验表明，nerandomilast可减少特发性肺纤维化患者FVC下降，安全性总体可控。nerandomilast将为临床治疗特发性肺纤维化提供潜在的解决方案，为患者带来新希望。点击文末“阅读原文/Read more”，即可访问NEJM官网阅读完整论文。推荐阅读得了肺病咳嗽不止！《柳叶刀》子刊：这种疗法止咳效果显著欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料：[1] Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2025 May 18. doi: 10.1056/NEJMoa2414108.免责声明：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：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「医学新视点」微信公众号留言联系。如有其他合作需求，请联系wuxi_media@wuxiapptec.com分享，点赞，在看，传递医学新知

PureTech hopes to launch a phase 3 trial of its deuterated version of Roche’s idiopathic pulmonary fibrosis drug Esbriet by the end of this year. The company showed promising results from a phase 2b trial at the American Thoracic Society International Conference Tuesday in San Francisco. \n One day after Boehringer Ingelheim presented so-so data from a successful trial of its highly touted idiopathic pulmonary fibrosis (IPF) candidate nerandomilast, PureTech has answered with results from a study of its IPF hopeful deupirfenidone.The new data from PureTech come after the company reported successful results from the phase 2b Elevate study in December after 26 weeks of therapy. The new round of preliminary figures highlight the durability of deupirfenidone’s effect through at least 52 weeks of treatment.In the trial, as of May 9, there were 101 patients who had received deupirfenidone for at least 52 weeks. Their lung function decline—as measured by forced vital capacity (FVC)—was at -32.8 mL over the treatment period, which is within the expected range (-30 mL to -50 mL) of natural decline in lung function in older, healthy people.Forced vital capacity is a measure of the amount of air exhaled during a lung capacity test.By comparison, in the first round of results, in patients who had received deupirfenidone for 26 weeks, the FVC decline came in at -21.5 mL. This result was also within the expected natural decline in lung function through the same time period in older, healthy adults, which is between -15 mL and -25 mL, according to PureTech.PureTech says it hopes to meet with the FDA by the end of the third quarter and to initiate a phase 3 trial of deupirfenidone by the end of the year. “The ability for a monotherapy to reduce lung function decline close to a level seen in healthy older adults and to sustain that effect over time without compromising tolerability, is not something we have seen with currently available therapies,” Toby Maher, M.D., Ph.D., the trial’s lead investigator and a professor of medicine at USC, said in a release. “Deupirfenidone has the potential to raise the bar for what patients and physicians can expect from IPF treatment.”The company presented the results Tuesday at the American Thoracic Society International Conference in San Francisco. Deupirfenidone is a deuterated version of Roche’s IPF drug Esbriet (pirfenidone), which achieved blockbuster status each year from 2018 to 2022 before it lost patent protection. Deuteration is a process in which hydrogen atoms in a compound are replaced with a heavier isotope of hydrogen. It can improve the pharmacokinetic properties of existing drugs, increasing their efficacy and safety.The Elevate trial enrolled four treatment arms receiving three daily doses. In addition to the dose of 825 mg of deupirfenidone producing a change in FVC of -21.5 mL at 26 weeks, a 550-mg dose of deupirfenidone was much less effective at -80.7 mL. An 801-mg dose of pirfenidone yielded a 51.6 mL decline in lung function, while the placebo arm saw a -112.5 mL FVC result.Preliminary pharmacokinetic data from the trial, comparing to pirfenidone 801 mg and deupirfenidone 825 mg, resulted in an approximately 50% increase in drug exposure, PureTech said. The increased drug exposure did not result in an increase in tolerability challenges, “suggesting that the deuterated structure of deupirfenidone may overcome the dose-limiting adverse events associated with pirfenidone,” the company added. Boehringer Ingelheim’s long-awaited results presentation Monday came after the company reported the top-line success of its trial in September. In the phase 3 study, patients were on background antifibrotic therapy, with 535 on Boehringer’s Ofev and 380 using Esbriet. Across the entire population, mean changes on FVC at 52 weeks were -114.7 mL on a high dose of nerandomilast and -183.5 mL on placebo.In response to the data, Leerink Partners analysts called the PDE4B inhibitor “incrementally better” than blockbuster Ofev but said it\'s still “disease-slowing rather than disease-halting.” The analysts added the “modest effect size” on lung function “is not likely to encourage an immediate change in IPF treatment.”