Justin M Oldham, Arata Azuma, Michael Kreuter, Toby M Maher, Fernando J. Martinez, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Y. Liu, Diane Zisa, Donald F. Zoz, Vincent Cottin, FIBRONEER-IPF trial investigators, P C Elias, G P De Stefano, A Casey, M J Fernandez, L A Wehbe, H M Castro, M Otaola, I Glaspole, N Goh, J Wrobel, T Corte, J Wheatley, D Chambers, G Keir, S Schembri, J Mackintosh, S Bowler, P Bremner, I Glaspole, C Lambers, S Handzhiev, M Steinmaurer, A Valipour, M Rauter, M Studnicka, G Brusselle, W Wuyts, A Froidure, B Bondue, C Dahlqvist, J Guiot, H Slabbynck, A S Rubin, M F Rabahi, G Zonzin, K M Storrer, E Mancuzo, A L Francisco Pez, F E Arimura, P Hernandez, C Ryerson, M Kalluri, J D Rolf, G Cox, S Anees, G Dion, M Mallet, H Manganas, E Millaire, D Assayag, D Marinescu, R S Silva Orellana, M R Salinas Fénero, Z Xu, J Cao, H Peng, Q Luo, J Xu, M Cao, F Li, H Zhu, T Bian, H Dai, F Wen, H Zhang, W Ma, W Huang, L Wang, Y Meng, K Hu, L Gao, X Li, X Xu, Q Hong, S Yang, G Shi, B Chen, T Zhao, W Li, Y Fu, Q Zhang, E Chen, X Wang, J Huang, L Rong, D Zhu, D Ljubicic
RATIONALE: In the randomized placebo-controlled FIBRONEER-IPF trial in patients with idiopathic pulmonary fibrosis, both nerandomilast 9 mg bid and 18 mg bid met the primary endpoint of reducing decline in forced vital capacity at week 52. Patients continued to receive randomized treatment after week 52, until the last patient had completed an end-of-treatment visit. OBJECTIVES: To assess the effects of nerandomilast over the full duration of follow-up in the FIBRONEER-IPF trial. METHODS: Time to first acute exacerbation of IPF, hospitalization for respiratory cause, or death (key secondary endpoint) and other time-to-event endpoints were assessed at final database lock. MEASUREMENTS AND MAIN RESULTS: 1177 patients were treated. Mean (SD) exposure to trial medication was 14.8 (5.0), 14.9 (5.0) and 14.7 (5.3) months in the placebo, nerandomilast 9 mg bid and nerandomilast 18 mg bid groups, respectively. Compared with placebo, the hazard ratio (95% CI) for the key secondary endpoint was 0.92 (0.69, 1.22) for nerandomilast 9 mg bid and 0.99 (0.75, 1.31) for nerandomilast 18 mg bid and the hazard ratio (95% CI) for death was 0.95 (0.61, 1.49) for nerandomilast 9 mg bid and 0.66 (0.41, 1.08) for nerandomilast 18 mg bid. Adverse events led to treatment discontinuation in 13.0%, 13.5% and 16.1% of the placebo, nerandomilast 9 mg bid and nerandomilast 18 mg bid groups, respectively. CONCLUSIONS: In the FIBRONEER-IPF trial, nerandomilast had no effect on the composite endpoint of time to first acute exacerbation of IPF, hospitalization for respiratory cause, or death, but nerandomilast 18 mg bid was associated with a numerically lower risk of death. Nerandomilast had a favorable safety profile, with a low rate of discontinuation due to adverse events.