Losmapimod Did Not Benefit Patients with Facioscapulohumeral Muscular Dystrophy

Treatment with losmapimod, a selective inhibitor of p38α/β MAPK, did not appear to provide any clinical benefit compared with placebo for patients with facioscapulohumeral muscular dystrophy (FSHD), according to results of the phase-3 REACH trial presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.

Results of a phase-2 study (ReDUX4) had shown that losmapimod had benefits on muscle function. However, according to data reported by Jeffrey Statland, MD, of the University of Kansas Medical Center, and colleagues at the conference, the phase 3 results did not replicate these findings.

REACH enrolled 260 patients aged 18 to 65 with either FSHD type 1 (n=242) or FSHD type 2 (n=18) and randomly assigned them to losmapimod 15 mg or placebo twice daily for 48 weeks.

The trial’s primary efficacy endpoint was change in total relative surface area (RSA) Q1–Q5 with 500 g wrist weight on reachable workspace. Secondary efficacy endpoints included change in shoulder abductor strength by hand-held dynamometry, muscle fat infiltration (MFI) in B muscles and response to the NeuroQoL-UE questionnaire.

No benefit was seen with losmapimod compared with placebo for the primary endpoint or any of the secondary endpoints.

Commenting in a press release, Pat Horn, chief medical officer of Fulcrum, which was developing losmapimod, said, “these results in patients receiving losmapimod when compared to baseline were similar to those observed in our phase 2 study. However, in contrast to what was seen in the ReDUX4 study as well as what has been reported in other FSHD studies, the patients receiving placebo in REACH did not show a decline in functional status as measured by RWS and shoulder dynamometry over the 48 weeks of the study.”

According to the study’s abstract, secondary and post hoc analyses are ongoing. However, Fulcrum Therapeutics announced that it would suspend future development.

Reference

Statland J, Rosenbohm A, Lopez de Munain Arregui A, et al. Topline Efficacy and Safety Results from REACH: Phase 3 Placebo-Controlled Trial of Losmapimod for Facioscapulohumeral Muscular Dystrophy (FSHD). O196. Presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.