Pamrevlumab for Idiopathic Pulmonary Fibrosis
Author:
Raghu Ganesh1, Richeldi Luca2, Fernández Pérez Evans R.3, De Salvo Maria Cristina4, Silva Rafael S.5, Song Jin Woo6, Ogura Takashi7, Xu Zuo Jun8, Belloli Elizabeth A.9, Zhang Xueping10, Seid Lorilyn L.10, Poole Lona10, , Bowler Simon11, Corte Tamera11, Holmes Mark11, Thien Francis11, Wheatley John11, Choi Sun-Mi11, Chung Man-Pyo11, Jeong Sunghwan11, Kim Yonghyun11, Lee Eun-Joo11, Lee Hyun-Kyung11, Park Choonsik11, Park Jong Sun11, Park Joo Hun11, Chi-Leung Lam David11, Chan Ming-Cheng11, Lee Kang-Yun11, Cao Jie11, Chen Juan11, Chen Rongchang11, Dai Huaping11, Fu Xiuhua11, Liang Zongan11, Luo Qun11, Shi Guochao11, Tong Zhaohui11, Wang Limin11, Yang Shuanying11, Yu Hongtao11, Zhang Huilan11, Zhang Jianchu11, Zhao Hui11, Wang Wei11, Meng Ying11, Peng Hong11, Ramaswamy Murali11, Hamblin Mark11, Fitzgerald John11, Gupta Nishant11, Dematte Jane11, Veeraraghavan Srihari11, O’Brien Thomas11, Luckhardt Tracy11, Lancaster Lisa11, Kokoszynska Marta11, Ettinger Neil11, Kaelin Thomas D.11, Siddiqi Ather11, Collins Bridget11, Scholand Mary Beth11, Antin-Ozerkis Danielle11, Hyun Kim11, Harden Christopher11, Averill Frank11, Mallea Jorge11, Bascom Rebecca11, Seeram Vandana11, Hajari Case Amy11, Britt Edward11, Shea Barry11, Criner Gerard11, Gotfried Mark11, Mageto Yolanda11, El Bayadi Sherif11, Reichner Cristina11, Mooney Joshua11, Hotchkin David11, Abrencillo Rodeo11, Boente Ryan11, Lee Joyce11, Betensley Alan11, Jeganathan Niranjan11, Walia Rajat11, Albertson Timothy11, Rosas Ivan11, Puppala Dileep11, Abraham Ladly11, Enelow Richard11, Bhatt Nitin11, Bandyopadhyay Debabratra11, Elias Pedro Carlos11, Bergna Miguel11, Garcia Gabriel Ricardo11, De Stefano Gaston11, Wehbe Luis Arturo11, Chirino Alejandro11, Rojas Ramon11, Otaola Maria11, Miranda Georgina11, Florenzano Matias11, Silva Orellana Rafael11, Glasinovich Valeska11, Shangina Olga11, Nikishenkov Alexey11, Kuzubova Natalia11
Affiliation:
1. University of Washington, Seattle 2. Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy 3. National Jewish Health, Denver, Colorado 4. Fundacion Respirar–Centro Médico, Buenos Aires, Argentina 5. Hospital Regional de Talca, Maule, Chile 6. Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea 7. Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan 8. Peking Union Medical College Hospital, Beijing, China 9. University of Michigan, Ann Arbor 10. FibroGen Inc, San Francisco, California 11. for the ZEPHYRUS-1 Study Investigators
Abstract
ImportanceCurrent 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.ObjectiveTo assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis.Design, Setting, and ParticipantsPhase 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.InterventionsPamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks.Main Outcomes and MeasuresThe 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.ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT03955146
Publisher
American Medical Association (AMA)
Cited by
8 articles.
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