美国南加州大学洛杉矶分校Toby M. Mahe团队研究了Nerandomilast在进行性肺纤维化患者中的应用。2025年5月19日出版的《新英格兰医学杂志》发表了这项成果。

Nerandomilast（BI 1015550）是一种口服磷酸二酯酶4B的优先抑制剂，具有抗纤维化和免疫调节特性。Nerandomilast已被证明可以减缓特发性肺纤维化的进展，但需要对其在其他类型的进展性肺纤维化中的作用进行评估。

在一项3期双盲试验中，研究组以1:1:1的比例随机分配患有进行性肺纤维化的患者，分别接受18mg剂量的Nerandomilast每日两次、9mg剂量的Nerandomilast每天两次或安慰剂，并根据背景治疗（尼达尼布与无）和高分辨率计算机断层扫描上的纤维化模式（常见的间质性肺炎样模式与其他模式）进行分层。主要终点是第52周用力肺活量（FVC）相对于基线的绝对变化，以毫升为单位。

共有1176名患者接受了至少一剂Nerandomilast或安慰剂治疗，其中43.5%的患者在基线时接受了背景尼达尼布治疗。第52周的FVC调整后平均变化为：18 mg组为-98.6 ml（95%置信区间[CI]，-123.7至-73.4），9 mg组为-84.6 ml（95%CI，-109.6至-59.7），安慰剂组为-165.8 ml（95%CI，-190.5至-141.0）。Nerandomilast 18 mg组和安慰剂组之间的调整后差异为67.2 ml（95%CI，31.9至102.5；P<0.001），Nerandomilast 9 mg组和安慰组之间的校正后差异为81.1 ml（95%CI，46.0至116.3；P<0.001）。最常见的不良事件是腹泻，Nerandomilast 18 mg组36.6%的患者报告腹泻，Nerandomilast 9 mg组29.5%的患者报告便秘，安慰剂组24.7%的患者报告腹痛。试验组中发生严重不良事件的患者比例相似。

研究结果表明，在进行性肺纤维化患者中，在52周的时间里，与安慰剂相比，Nerandomilast治疗导致FVC下降幅度较小。

附：英文原文

Title: Nerandomilast in Patients with Progressive Pulmonary Fibrosis

Author: Toby M. Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M. Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S. Wijsenbeek, Emmanuelle Clerisme-Beaty, Carl Coeck, Hui Gu, Ivana Ritter, Arno Schlosser, Susanne Stowasser, Florian Voss, Gerrit Weimann, Donald F. Zoz, Fernando J. Martinez

Issue&Volume: 2025-05-19

Abstract:

Background

Nerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory properties. Nerandomilast has been shown to slow the progression of idiopathic pulmonary fibrosis, but an assessment of its effects in other types of progressive pulmonary fibrosis is needed.

Methods

In a phase 3, double-blind trial, we randomly assigned patients with progressive pulmonary fibrosis in a 1:1:1 ratio to receive nerandomilast at a dose of 18 mg twice daily, nerandomilast at a dose of 9 mg twice daily, or placebo, with stratification according to background therapy (nintedanib vs. none) and fibrotic pattern on high-resolution computed tomography (usual interstitial pneumonia-like pattern vs. other patterns). The primary end point was the absolute change from baseline in the forced vital capacity (FVC), measured in milliliters, at week 52.

Results

A total of 1176 patients received at least one dose of nerandomilast or placebo, of whom 43.5% were taking background nintedanib therapy at baseline. The adjusted mean change in the FVC at week 52 was 98.6 ml (95% confidence interval [CI], 123.7 to 73.4) in the nerandomilast 18-mg group, 84.6 ml (95% CI, 109.6 to 59.7) in the nerandomilast 9-mg group, and 165.8 ml (95% CI, 190.5 to 141.0) in the placebo group. The adjusted difference between the nerandomilast 18-mg group and the placebo group was 67.2 ml (95% CI, 31.9 to 102.5; P<0.001), and the adjusted difference between the nerandomilast 9-mg group and the placebo group was 81.1 ml (95% CI, 46.0 to 116.3; P<0.001). The most frequent adverse event was diarrhea, reported in 36.6% of the patients in the nerandomilast 18-mg group, 29.5% of those in the nerandomilast 9-mg group, and 24.7% of those in the placebo group. Serious adverse events occurred in similar percentages of patients in the trial groups.

Conclusions

In patients with progressive pulmonary fibrosis, treatment with nerandomilast led to a smaller decline in the FVC than placebo over a period of 52 weeks.

DOI: NJ202505190000011

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2503643