Pirfenidone

2025年10月8日，美国食品药品监督管理局（FDA）正式批准勃林格殷格翰（Boehringer Ingelheim）新药 Jascayd（nerandomilast）片剂上市，用于治疗罕见且致命的特发性肺纤维化（IPF）。 这是十余年来首个获批的 IPF 新机制疗法，也是全球首个选择性磷酸二酯酶 4B（PDE4B）抑制剂，为进展性肺纤维化患者带来全新的治疗选择。 十年破冰：首个 PDE4B 抑制剂获批 IPF 是一种病因未明、进行性加重的间质性肺病，患者中位生存期仅 3–5 年，现有药物只能延缓肺功能下降，无法逆转纤维化进程。自 2014 年尼达尼布（nintedanib）和吡非尼酮（pirfenidone）获批以来，再无新药问世，临床需求远未被满足。 FIBRONEER-IPF随机、安慰剂对照、双盲试验（NCT05321069）和试验2 （NCT04419506）的数据支持本次批准，这是10多年来IPF的首次批准。在该研究中，与安慰剂相比，磷酸二酯酶4抑制剂被发现可以减缓肺功能下降，该研究包括1177名患者。 Jascayd 通过选择性抑制 PDE4B，兼具抗炎与抗纤维化双重作用，可显著减缓肺功能衰退。结果如下： 数据来源：梅斯呼吸新前沿 FIBRONEER-IPF试验显示，与安慰剂相比，接受nerandomilast治疗的患者从基线开始的绝对FVC下降明显更少。在nerandomilast队列中，FVC调整后的平均下降在18 mg组为-114.7mL，在9 mg组为-138.6 mL。在安慰剂组，调整后的平均下降量为-183.5 mL。 另外，FIBRONEER™-ILD（NCT05321082）是一项双盲、随机、安慰剂对照试验，旨在评估nerandomilast在进展性纤维化（PPF）患者中至少治疗52周时的疗效和安全性。治疗第52周时的关键疗效结果已发布于《新英格兰医学杂志》，结果如下： 数据来源：梅斯呼吸新前沿 今年2月和5月，勃林格殷格翰中国先后向国家药监局（NMPA）了nerandomilast治疗成人特发性肺纤维化（IPF）和成人进展性肺纤维化（Progressive Pulmonary Fibrosis，PPF）的上市申请，并被纳入优先审评程序。此外，其PPF适应症还获得FDA突破性疗法认定。 预计今年底或2026 年上半年有望在中国获批，届时将通过医保谈判提高药物可及性。业内人士估算，若纳入医保，Jascayd 年治疗成本有望控制在 10 万元人民币以内，显著低于现有进口药物。 结束语： Jascayd 不仅可以作为单药一线使用，也为无法耐受现有药物或疗效不足的患者提供了替代方案。随着 Jascayd 的获批，全球抗纤维化治疗正式进入“三驾马车”时代。业内预期，未来 5 年还将有针对 CTGF、LPA1受体激动剂admilparant 等新靶点的药物递交上市申请，为罕见肺纤维化患者带来更多生存希望。

The FDA on Tuesday approved Boehringer Ingelheim's Jascayd (nerandomilast), making it the first new therapy for idiopathic pulmonary fibrosis (IPF) in more than a decade. The oral PDE4 inhibitor will join a small group of drugs — Roche's Esbriet (pirfenidone) and Boehringer's own Ofev (nintedanib) — used to slow the progressive scarring that robs IPF patients of lung function.The approval is based on results from the Phase III FIBRONEER-IPF trial, which enrolled more than 1100 adults with IPF. Patients taking Jascayd twice daily experienced a smaller decline in forced vital capacity (FVC) over 52 weeks. Those on the 18-mg dose saw an adjusted mean change in FVC of -114.7 mL versus almost -184 mL for placebo, while the lower 9-mg dose group fared slightly worse, but still showed a benefit.A companion Phase III study, FIBRONEER-ILD, in patients with progressive pulmonary fibrosis (PPF) also showed a greater benefit with Jascayd. The 9-mg and 18-mg cohorts saw mean adjusted FVC changes of -84.6 mL and -98.6 mL, respectively, compared with almost -166 mL among placebo recipients. Boehringer has also submitted a US regulatory filing for the PDE4 inhibitor to treat PPF.Diarrhoea was the most frequent side effect, affecting about 30% to 41% of Jascayd-treated patients across both studies.Despite the statistical win on efficacy, one key opinion leader (KOL) previously urged caution about what the findings actually mean for patients."They did meet the primary endpoint of FVC, but not the secondary endpoints, which looked at clinical outcomes," noted Allison Reiss, an internal medicine specialist and head of the inflammation laboratory at NYU Langone Hospital, in a recent interview with FirstWord. "What does that mean in everyday life to the patient? The answer is very little because it does not seem to have any advantage in terms of keeping you out of the hospital or alive longer." See – KOL Views Q&A: Boehringer's nerandomilast works in IPF but needs to get in line.The limitations echo those of United Therapeutics' Tyvaso (treprostinil), another recently tested therapy for IPF that also improved FVC in the Phase III TETON-2 study, though the results had KOL Paolo Spagnolo, a professor of respiratory medicine at the University of Padua, questioning its real-world impact. However, while Tyvaso is inhaled four times daily, Jascayd's less onerous dosing schedule could make it the more convenient option for patients.