Facioscapulohumeral Muscular Dystrophy (FSHD) Disease Progression and Losmapimod Efficacy Assessed by Reachable Workspace in Both Arms


Clinical Trials

Poster Number: T343


Rabi Tawil, MD, University of Rochester Medical Center, Joost Kools, MD, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Marie-Helene Jouvin, MD, Fulcrum Therapeutics, John Jiang, PhD, Fulcrum Therapeutics

Background: In phase 2 studies of losmapimod, a p38α/β MAPK inhibitor, for FSHD, efficacy endpoints included reachable workspace (RWS), a computerized three-dimensional assessment of shoulder mobility, in dominant and non-dominant arms. This phase-2 post-hoc analysis explores averaging RWS measurements across both arms.
Methods: In the 52-week Open-Label Study (OLS) and 48-week randomized, placebo-controlled ReDUX4 trial, patients aged 18–65 with FSHD1 received twice-daily losmapimod 15 mg or placebo (ReDUX4 only). Efficacy measures included RWS total relative surface area (RSA) across five quadrants (scale: 0–1.25) with wrist weights, dynamometry to assess shoulder abduction strength, and whole-body muscle MRI composite scores: lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI). Results for RSA averaged across both arms are compared with previously reported dominant-arm results. Efficacy correlations were assessed by Spearman’s rank correlation.
Results: Analyses included 14 OLS and 80 ReDUX4 (40 losmapimod, 40 placebo) patients. At 52 weeks in OLS, RSA averaged across both arms improved 0.037 from baseline vs 0.043 in the dominant arm. In ReDUX4 over 48 weeks, the treatment benefit shown by RSA averaged across both arms was consistent with dominant-arm improvement (change from baseline, losmapimod-placebo difference 0.047; [P=0.014], 0.049 [P=0.016], respectively). At 48 weeks, RSA averaged across both arms correlated moderately to strongly with shoulder strength, LMV, and MFF (r for shoulder strength: 0.865, 0.862; LMV: 0.666, 0.603; MFF: –0.747, –0.493; losmapimod and placebo, respectively; all P<0.01). RSA also correlated with MFI in the losmapimod (r: –0.678; P=0.0005), but not the placebo group. Dominant-arm correlations were similar. Conclusions: These results support the potential benefits of using total RSA with weight averaged over both arms as a clinical endpoint. This bilateral assessment of RSA provides a robust measure of FSHD functional impairment and disease progression, aligning with secondary endpoints of muscle strength and structure.