Pamrevlumab did not meet its primary endpoint for non-ambulatory patients with Duchenne Muscular Dystrophy: the LELANTOS-1 trial

Background In Duchenne muscular dystrophy (DMD), fibrosis is linked to connective tissue growth factor (CTGF) overexpression. Pamrevlumab, a fully human monoclonal antibody, inhibits CTGF activity and showed promise as a DMD treatment in a phase 2 trial. Objective LELANTOS-1 ( NCT04371666 ) was a global phase 3 study of the safety and efficacy of pamrevlumab for non-ambulatory males ≥12 years old with DMD. Methods Patients 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 total Performance of Upper Limb (PUL) v2.0 score change from baseline to Week 52 in the modified intent-to-treat (mITT) set (baseline PUL score ≥2). Treatment-emergent adverse events (TEAEs) were noted. Patients who completed the main study period were eligible to enroll in the open-label extension (OLE). Results Ninety-eight patients (mean [SD] age, 15.5 [2.57] years) enrolled; 48 received pamrevlumab and 49 received placebo. Between-group baseline characteristics were similar. In the mITT set (mean [SD] age, 15.5 [2.64] years; pamrevlumab, n=41; placebo, n=42), the total PUL v2.0 score change was not significantly different ( p =0.8802). The pamrevlumab group had more grip strength deterioration than placebo in dominant ( p =0.0161) and nondominant hands ( p =0.0052). Most patients (pamrevlumab, n=45/48 [93.8%]; placebo, n=48/49 [98.0%]) experienced TEAEs (most mild/moderate). One death occurred in the pamrevlumab group (unrelated to study drug). The OLE mITT set included 72 patients. OLE efficacy and safety were consistent with the main study period. No deaths occurred during the OLE. Conclusions Pamrevlumab failed to meet the primary endpoint. Its future as a DMD treatment is uncertain. Trial Registration ClinicalTrials.gov Identifier: NCT04371666