LELANTOS-2: primary and secondary endpoints were not met by pamrevlumab in ambulatory patients with Duchenne Muscular Dystrophy (DMD)


Clinical Trials

Poster Number: M152


Brenda L. Wong, University of Massachusetts Medical School, Duchenne Muscular Dystrophy Center, John F. Brandsema, MD, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Anne M. Connolly, MD, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Han Phan, MD, Rare Disease Research, Yann Péréon, Centre de Référence Maladies Neuromusculaires AOC, Filnemus, Hôpital Hôtel-Dieu, Silvana De Lucia, Institute I-Motion, Hôpital Armand Trousseau, Yi Dai, MD, PhD, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Ziyi Chen, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Craig Campbell, University of Western Ontario, Department of Paediatrics, Children’s Hospital London Health Sciences, Valeria Sansone, MD, Centro Clinico NeMO Milano, Stéphanie Delstanche, MD, University Department of Neurology, Centre Hospitalier Régional de la Citadelle, Steven Wang, FibroGen, Inc., Olga V. Gambetti, FibroGen, Inc., Ewa Carrier, MD, FibroGen, Inc.

Background: In DMD, fibrosis due to absent or dysfunctional dystrophin protein has been linked to overexpression of connective tissue growth factor (CTGF). Pamrevlumab is a fully human monoclonal antibody that binds to and inhibits the activity of CTGF.

Objectives: LELANTOS-2 (NCT04632940) was a global Phase III, randomized, double-blind, placebo-controlled multicenter study of the safety and efficacy of pamrevlumab for ambulatory males 6 to <12 years old with DMD. The primary endpoint was change in North Star Ambulatory Assessment (NSAA) total score from baseline to Week 52. Secondary endpoints included changes at Week 52 in 4-stair climb velocity, 10-meter walk/run test, time to stand, and time to loss of ambulation. Treatment-emergent adverse events (TEAEs) were noted. Results: In all, 73 patients were randomized 1:1 to receive pamrevlumab 35 mg/kg by intravenous infusion every 2 weeks for 52 weeks (n=37) or placebo (n=36). All patients received systemic glucocorticoids (deflazacort or prednisone/prednisolone) during the study period. Demographics and baseline clinical characteristics were similar between groups. The difference in change in NSAA score was not significant (least squares [LS] mean [SE]: pamrevlumab, –3.022 [0.5505] vs. placebo, –2.494 [0.6962]; p=0.5553). Across all secondary endpoints, there were no significant differences between patients treated with pamrevlumab and placebo. Nearly all patients (pamrevlumab, n=35 [97.2%]; placebo, n=35 [97.2%]) experienced TEAEs (most mild to moderate). No deaths occurred in either treatment group. Conclusions: Pamrevlumab failed to meet its primary and secondary endpoints in the LELANTOS-2 pivotal Phase III study for ambulatory males with DMD. Pamrevlumab was generally well tolerated and no new safety concerns were identified for patients with DMD.