Pamrevlumab for Idiopathic Pulmonary Fibrosis
Ganesh Raghu, Luca Richeldi, Evans R. Fernández Pérez, María Cristina De Salvo, Rafael S. Silva, Jin Woo Song, Takashi Ogura, Zuo Jun Xu, Elizabeth A. Belloli, Xueping Zhang, Lorilyn L. Seid, Lona Poole, ZEPHYRUS-1 Study Investigators, Simon Bowler, Tamera J. Corte, Mark Holmes, Francis Thien, John Wheatley, Choi Sun-Mi, Man-Pyo Chung, Sung-Hwan Jeong, Yonghyun Kim, Eunjoo Lee, Hyun-Kyung Lee, Choon‐Sik Park, Jong Sun Park, Joo Hun Park, David Lam, Ming-Cheng Chan, Kang‐Yun Lee, Jie Cao, Juan Chen, Rongchang Chen, Huaping Dai, Xiuhua Fu, Zongan Liang, Qun Luo, Guochao Shi, Zhaohui Tong, Limin Wang, Shuanying Yang, Hongtao Yu, Huilan Zhang, Jianchu Zhang, Hui Zhao, Wei Wang, Ying Meng, Hong Peng, Murali Ramaswamy, Mark Hamblin, John Fitzgerald, Nishant Gupta, Jane E. Dematte, Srihari Veeraraghavan, Thomas O’Brien, Tracy Luckhardt, Lisa Lancaster, M. Kokoszynska, Neil Ettinger, Thomas D. Kaelin, Ather Siddiqi, Bridget F. Collins, Mary Beth Scholand, Danielle Antin‐Ozerkis, Kim Hyun, Christopher Harden, Frank Averill, Jorge M. Mallea, Rebecca Bascom, Vandana Seeram, Amy Hajari Case, E. James Britt, Barry S. Shea, Gerard J. Criner, Mark H. Gotfried, Yolanda Mageto, Sherif El Bayadi, Cristina Reichner, Joshua J. Mooney, David Hotchkin, Rodeo Abrencillo, R. Boente, Joyce Lee, Alan Betensley, Niranjan Jeganathan, Rajat Walia, Timothy Albertson, Iván O. Rosas, Dileep Puppala, Ladly Abraham, Richard I. Enelow, Nitin Bhatt, Debabratra Bandyopadhyay, Pedro Carlos Elias, Miguel Bergna, Gabriel Ricardo Garcia, Gaston De Stefano, Luis Arturo Wehbe, Alejandro Chirino, Ramón Luévanos Rojas
Abstract
Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.