Pamrevlumab for Idiopathic Pulmonary Fibrosis
Authors: Raghu Ganesh , Richeldi Luca , Fernández Pérez Evans R. , De Salvo Maria Cristina , Silva Rafael S. , Song Jin Woo , Ogura Takashi , Xu Zuo Jun , Belloli Elizabeth A. , Zhang Xueping , Seid Lorilyn L. , Poole Lona ,   ZEPHYRUS-1 Study Investigators, Bowler Simon , Corte Tamera , Holmes Mark , Thien Francis , Wheatley John , Choi Sun-Mi , Chung Man-Pyo , Jeong Sunghwan , Kim Yonghyun , Lee Eun-Joo , Lee Hyun-Kyung , Park Choonsik , Park Jong Sun , Park Joo Hun , Chi-Leung Lam David , Chan Ming-Cheng , Lee Kang-Yun , Cao Jie , Chen Juan , Chen Rongchang , Dai Huaping , Fu Xiuhua , Liang Zongan , Luo Qun , Shi Guochao , Tong Zhaohui , Wang Limin , Yang Shuanying , Yu Hongtao , Zhang Huilan , Zhang Jianchu , Zhao Hui , Wang Wei , Meng Ying , Peng Hong , Ramaswamy Murali , Hamblin Mark , Fitzgerald John , Gupta Nishant , Dematte Jane , Veeraraghavan Srihari , O’Brien Thomas , Luckhardt Tracy , Lancaster Lisa , Kokoszynska Marta , Ettinger Neil , Kaelin Thomas D. , Siddiqi Ather , Collins Bridget , Scholand Mary Beth , Antin-Ozerkis Danielle , Hyun Kim , Harden Christopher , Averill Frank , Mallea Jorge , Bascom Rebecca , Seeram Vandana , Hajari Case Amy , Britt Edward , Shea Barry , Criner Gerard , Gotfried Mark , Mageto Yolanda , El Bayadi Sherif , Reichner Cristina , Mooney Joshua , Hotchkin David , Abrencillo Rodeo , Boente Ryan , Lee Joyce , Betensley Alan , Jeganathan Niranjan , Walia Rajat , Albertson Timothy , Rosas Ivan , Puppala Dileep , Abraham Ladly , Enelow Richard , Bhatt Nitin , Bandyopadhyay Debabratra , Elias Pedro Carlos , Bergna Miguel , Garcia Gabriel Ricardo , De Stefano Gaston , Wehbe Luis Arturo , Chirino Alejandro , Rojas Ramon , Otaola Maria , Miranda Georgina , Florenzano Matias , Silva Orellana Rafael , Glasinovich Valeska , Shangina Olga , Nikishenkov Alexey , Kuzubova Natalia 
Published: May 2024

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