FibroGen's Duchenne Muscular Dystrophy Antibody Pamrevlumab Falls Short in Phase 3


The study did not meet its primary end point of change from baseline in Performance of the Upper Limb 2.0 score at 1 year.

Elias Kouchakji, MD

Elias Kouchakji, MD

Duchenne muscular dystrophy continues to be a challenging disease to tackle, taking down another promising late-stage investigational drug. FibroGen reported that its phase 3 LELANTOS-1 clinical trial, which examined the effects of pamrevlumab in non-ambulatory patients with Duchenne muscular dystrophy (DMD), failed to meet its primary end point.1

Although safe and generally well-tolerated, the combination treatment with the investigational antibody plus corticosteroids failed to demonstrate meaningful improvements in the Performance of the Upper Limb 2.0 score compared with baseline.

“While disappointed with these results, we look forward to sharing the data at a future medical conference to contribute towards the understanding of this devastating disease,” said Enrique Conterno, chief executive officer, FibroGen, in a statement.1 “FibroGen would like to thank the patients, caregivers and clinical trial investigators for their dedication in participating in this study."

A total of 92 male participants aged 12 and older were enrolled in the double-blind, placebo-controlled study which randomly assigned them to receive treatment with either pamrevlumab plus systemic corticosteroid or placebo plus corticosteroid over a 52-week treatment period. Participants received 35 mg/kg of the antibody or placebo intravenously every 2 weeks plus oral cortocosteroid for the year-long study, at which point they could be rolled over into an open-label extension.

Beyond the primary end point, participants were also evaluated on change from baseline in percent predicted forced vital capacity, grip strength of the hands, left ventribular ejection fraction percdentage, and percent predicted peak expiratory flow, all assessed at 52 weeks.

Notably, the first-in-class connective tissue growth factor (CTGF) inhibitor antibody is also being evaluated in an ongoing second phase 3 trial, LELANTOS-2, which is evaluating the drug in ambulatory patients with DMD age 6 to 12 years. That study, which completed enrollment in June 2022,2 includes 73 participants randombly assigned to recieve either pamrevlumab 35 mg/kg intravenously every 2 weeks for 52 weeks plus oral corticosteroid, or placebo plus oral corticosteroid. The primary end point for that trial is change from baseline in North Star Ambulatory Assessment total score at 52 weeks. Topline data from that trial are expected later this year.

“We’ve seen that this monoclonal antibody can block that CTGF from continuing to activate the myofibroblasts, reduce the motility and invasion, or the proliferation of the fibrosis,” Elias Kouchakji, MD, senior vice president, clinical development, drug safety, and pharmacovigilance at FibroGen, told NeurologyLive in a previous interview. “There are many diseases that fibrosis is well defined, including idiopathic pulmonary fibrosis, interstitial lung diseases in general, DMD, invasive liver cirrhosis, and other cardiovascular diseases. By blocking CTGF, we are reducing the invasion of the fibrosis, blocking the activation of myofibroblasts, and reducing the deposition in the remodeling of the fibrosis.”

Outside of DMD, FibroGen is evaluating pamrevlumab in 2 phase 3 clinical trials in idiopathic pulmonary fibrosis, the first of which is due to read out topline data this year.

Pamrevlumab was granted orphan drug designation for the treatment of DMD in 2019, followed by rare pediatric disease and fast track designations in April 2021.

1. FibroGen Announces Topline Results from LELANTOS-1 Phase 3 Clinical Study of Pamrevlumab in Non-Ambulatory Patients with Duchenne Muscular Dystrophy. News release. FibroGen Inc. June 7, 2023. Accessed June 7, 2023.
2. FibroGen Announces Completion of Patient Enrollment in LELANTOS-2, a Phase 3 Clinical Study of Pamrevlumab in Duchenne Muscular Dystrophy. News release. FibroGen. June 8, 2022. Accessed June 8, 2022.
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