Effect of nerandomilast on survival in patients with pulmonary fibrosis

BACKGROUND: In the placebo-controlled FIBRONEER-IPF and FIBRONEER-ILD trials in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), the key secondary endpoint was not met but numerical benefits of nerandomilast on time to death (a secondary endpoint) were observed. We further investigated the robustness of the effect of nerandomilast on survival. METHODS: In both trials, the primary analysis of time to death was based on all deaths except those after lung transplant, using a Cox proportional hazards model. We performed sensitivity analyses of the impact of covariates, tipping point analyses, and supplementary analyses of deaths during and shortly after treatment and the impact of intercurrent events. We assessed time to death by exposure to nerandomilast (trough concentration at steady state). RESULTS: placebo was reduced by 33% (hazard ratio: 0.67 [95% CI: 0.49, 0.90]; p=0.009) with nerandomilast 9 mg bid and by 43% (hazard ratio: 0.57 [95% CI: 0.41, 0.78]; p<0.001) with nerandomilast 18 mg bid. Sensitivity analyses and supplementary analyses were consistent with the primary analysis of time to death. Tipping point analyses demonstrated a very low likelihood that the benefit of nerandomilast on mortality was due to missing data. Exposure-response analyses indicated that a higher plasma exposure to nerandomilast was associated with a lower risk of death. CONCLUSION: These analyses support the use of nerandomilast 18 mg bid to improve survival in patients with IPF and PPF.

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Publication Details

Journal
European Respiratory Journal
Published
2026-07-30
DOI
https://doi.org/10.1183/13993003.00338-2026
Primary Topic
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
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article
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article

Effect of nerandomilast on survival in patients with pulmonary fibrosis

Ivana Ritter, Vincent Cottin, Shervin Assassi, Arata Azuma et al.
European Respiratory Journal
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
article

Effect of nerandomilast on survival in patients with pulmonary fibrosis

Ivana Ritter, Vincent Cottin, Shervin Assassi, Arata Azuma, Toby M. Maher, Claudia Valenzuela, Donald F. Zoz, Gerrit Weimann, Susanne Stowasser, Hui Gu, Luca Richeldi, Marlies S. Wijsenbeek, Steve Choy, Anna-Maria Hoffmann-Vold, Fernando J. Martinez, Michael Kreuter, Justin M. Oldham
article en

Abstract

BACKGROUND: In the placebo-controlled FIBRONEER-IPF and FIBRONEER-ILD trials in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), the key secondary endpoint was not met but numerical benefits of nerandomilast on time to death (a secondary endpoint) were observed. We further investigated the robustness of the effect of nerandomilast on survival. METHODS: In both trials, the primary analysis of time to death was based on all deaths except those after lung transplant, using a Cox proportional hazards model. We performed sensitivity analyses of the impact of covariates, tipping point analyses, and supplementary analyses of deaths during and shortly after treatment and the impact of intercurrent events. We assessed time to death by exposure to nerandomilast (trough concentration at steady state). RESULTS: placebo was reduced by 33% (hazard ratio: 0.67 [95% CI: 0.49, 0.90]; p=0.009) with nerandomilast 9 mg bid and by 43% (hazard ratio: 0.57 [95% CI: 0.41, 0.78]; p<0.001) with nerandomilast 18 mg bid. Sensitivity analyses and supplementary analyses were consistent with the primary analysis of time to death. Tipping point analyses demonstrated a very low likelihood that the benefit of nerandomilast on mortality was due to missing data. Exposure-response analyses indicated that a higher plasma exposure to nerandomilast was associated with a lower risk of death. CONCLUSION: These analyses support the use of nerandomilast 18 mg bid to improve survival in patients with IPF and PPF.

European Respiratory Journal
Université Claude Bernard Lyon 1 (FR), Università Cattolica del Sacro Cuore (IT), University of Southern California (US), Oslo University Hospital (NO), UMass Memorial Health Care (US), Boehringer Ingelheim (Germany) (DE), Johannes Gutenberg University Mainz (DE), University of Zurich (CH), University of Michigan (US), Erasmus MC (NL), Agostino Gemelli University Polyclinic (IT), Seirei Mikatabara General Hospital (JP), University Medical Center of the Johannes Gutenberg University Mainz (DE), University Hospital of Zurich (CH), Hospices Civils de Lyon (FR), Boehringer Ingelheim (Brazil) (BR), Michigan Medicine (US), Hospital Universitario de La Princesa (ES), Hôpital Louis Pradel (FR), Boehringer Ingelheim (China) (CN), Istituti di Ricovero e Cura a Carattere Scientifico (IT), The University of Texas Health Science Center (US), Boehringer Ingelheim (United States) (US), UMass Memorial Medical Center (US), Imperial College London (GB), Universidad Autónoma de Madrid (ES), Nippon Medical School (JP), Erasmus University Rotterdam (NL)
Good health and well-being
Openalex Percentile: Top 10%
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
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