Losmapimod Improves Function and Slows Progression of Facioscapulohumeral Muscular Dystropy 

Although the phase 2b ReDUX4 study (NCT04264442) of losmapimod (Fulcrum Therapeutics, Cambridge, MA) for treatment of facioscapulohumeral muscular dystrophy (FSHD) did not meet prespecified outcomes, clinical improvements were seen. Participants treated with losmapimod vs placebo had decreased muscle fat infiltration (P=0.01) decreased as did functional decline. 

Participants treated with the therapy showed decreased progression in the treatment efficacy measure of muscle fat infiltration as measured in intermediate muscles, those most likely to change. Those treated with losmapimod also had up to 1.5% improved accessible surface area on Reachable WOrkspace (RWS) measures (P<.05) with a 500 g weight on the wrist.

Participants treated with losmapimod were also 4 times more likely to have improvement on the Patient Global Impression of Change assessment (P=.02) compared with those who received placebo. Motor function measures, however, did not differ with losmapimod treatment vs placebo.

“These results provide strong support that treatment with losmapimod has a meaningful clinical benefit in relevant measures of FSHD disease progression, despite the challenges of measuring DUX4,” said Rabi Tawil, MD, professor of Neurology, University of Rochester Medical Center. “I am enthusiastic about the potential for losmapimod to offer meaningful improvements in preserving muscle function and patient quality of life.”

Participants in the study (n=80) were randomly assigned to receive 30 mg/day losmapimod or placebo in 2 divided doses. These data were presented at the FSHD International Research Congress. 

Losmapimod is a microtuble-associated protein (MAP) kinase inhibitor that modulates double homeobox 4 (DUX4) gene expression, thought to be causative of FSHD. Losmapimod, however, did not result in lower levels of DUX4 compared with placebo on muscle biopsy. Study investigators suggest this may be caused by heterogeneity of DUX4 expression and the challenge in consistently measuring DUX4 levels.