Pamrevlumab failed to meet primary and secondary endpoints for nonambulatory patients with Duchenne Muscular Dystrophy (DMD) in LELANTOS-1

Topic:

Clinical Trials

Poster Number: M165

Author(s):

John Brandsema, 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, Brenda Wong, M.D., U Mass Chan Med School, Han Phan, MD, Rare Disease Research, Xiaotang Cai, PhD, West China Second Hospital of Sichuan University, Cuixia Tian, MD, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Silvana De Lucia, Institute I-Motion, Hôpital Armand Trousseau, Stanley F. Nelson, MD, University of California‒Los Angeles, Yann Péréon, Centre de Référence Maladies Neuromusculaires AOC, Filnemus, Hôpital Hôtel-Dieu, Stefano C. Previtali, INSPE and Division of Neuroscience, IRCCS Ospedale San Raffaele, Steven Wang, FibroGen, Inc., Olga V. Gambetti, FibroGen, Inc., Ewa Carrier, MD, FibroGen, Inc.

Background: In DMD, fibrosis is linked to connective tissue growth factor (CTGF) overexpression. Pamrevlumab, a fully human monoclonal antibody, inhibits CTGF activity.

Objectives: LELANTOS-1 (NCT04371666) was a global Phase III, randomized, double-blind, placebo-controlled study of pamrevlumab safety and efficacy for nonambulatory DMD males ≥12 years old. Primary endpoint was total Performance of Upper Limb (PUL) V2.0 score change (baseline to Week 52) in the modified intent-to-treat (mITT) set (patients with baseline PUL ≥2). Secondary endpoints were Week-52 changes in percent-predicted forced vital capacity, mid-level PUL score, grip strength, and left ventricular ejection fraction percentage. Treatment-emergent adverse events (TEAEs) were noted among patients who received a dose of study drug. Patients who completed the main study period could enroll in the open-label extension (OLE).

Results: Ninety-eight patients (mean [SD] age, 15.5 [2.57] years) were enrolled; 97 received pamrevlumab 35 mg/kg intravenously every 2 weeks (n=48) or placebo (n=49). All received systemic glucocorticoids (deflazacort or prednisone/prednisolone). Demographics and baseline clinical characteristics were similar between groups. The mITT set comprised 83 patients (mean [SD] age, 15.5 [2.64] years; pamrevlumab, n=41; placebo, n=42). The difference in total PUL V2.0 score change was not significant (p=0.8802). The pamrevlumab group had more grip strength deterioration than placebo in dominant (p=0.0161) and nondominant hands (p=0.0052). Differences in other secondary endpoints were not statistically significant. Most patients (pamrevlumab, n=45/48 [93.8%]; placebo, n=48/49 [98.0%]) experienced TEAEs (most mild to moderate). One death occurred in the pamrevlumab group (unrelated to study drug). Compliance was high (pamrevlumab, 93.2%; placebo, 95.4%). The OLE mITT set included 72 patients; all received pamrevlumab 35 mg/kg every 2 weeks. Efficacy and safety in the OLE were consistent with the main study period. No deaths occurred during the OLE.

Conclusions: Pamrevlumab failed to meet the primary and secondary endpoints, but was well tolerated in DMD patients.