Pamrevlumab did not meet its primary endpoint for ambulatory patients with Duchenne Muscular Dystrophy: the LELANTOS-2 trial

BackgroundIn Duchenne muscular dystrophy (DMD), fibrosis is linked to connective tissue growth factor (CTGF) overexpression. Pamrevlumab, a fully human monoclonal antibody that inhibits CTGF activity, showed promise as a DMD treatment in a phase 2 trial. ObjectiveLELANTOS-2 (NCT04632940) was a global phase 3 study of the safety and efficacy of pamrevlumab for ambulatory males 6 to <12 years old with DMD. MethodsPatients were randomized 1:1 to pamrevlumab 35 mg/kg every 2 weeks for 52 weeks or placebo. All received a stable corticosteroid regimen (deflazacort or prednisone/prednisolone). Primary endpoint was change in North Star Ambulatory Assessment (NSAA) total score from baseline to Week 52. Treatment-emergent adverse events (TEAEs) were noted. Patients who completed the main study period were eligible to enroll in the open-label extension (OLE). ResultsSeventy-three patients enrolled (mean [SD] age, 9.0 [1.5] years; pamrevlumab [n=37], placebo [n=36]). Between-group baseline characteristics were similar. 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 or placebo. Nearly all patients (pamrevlumab, n=35 [97.2%]; placebo, n=35 [97.2%]) experienced TEAEs (most mild/moderate). Sixty-eight (34 from each original treatment group) patients enrolled in and received pamrevlumab during the OLE. OLE efficacy and safety were consistent with the main study period. No deaths occurred. ConclusionsPamrevlumab failed to meet its primary endpoint. Its future as a DMD treatment is uncertain.