## Losmapimod Shows Tangible Clinical Benefits in FSHD Treatment: Fulcrum Therapeutics' Phase 2b Trial Data Published

Fulcrum Therapeutics has released Phase 2b clinical trial results for losmapimod in treating facioscapulohumeral muscular dystrophy (FSHD), with findings now published in *The Lancet Neurology*. The data reveal promising improvements across multiple clinical measures, advancing understanding of how this investigational therapy may address this rare progressive muscle disorder.

**Trial Design and Patient Demographics**

The ReDUX4 trial enrolled 80 participants with FSHD type 1 across sites in the United States, Canada, and Europe. Patients aged 18 to 65 received either losmapimod at 15 mg twice daily or placebo for 48 weeks, providing a substantial evidence base from a geographically diverse population.

**Key Clinical Outcomes**

While the primary endpoint—reduction in DUX4-driven gene expression in muscle tissue—did not demonstrate statistical significance between treatment and placebo groups, secondary measures told a different story. Participants receiving losmapimod showed measurable improvements in muscle fat infiltration, a hallmark pathological feature of FSHD. Additionally, reachable workspace, a functional metric assessing shoulder girdle mobility, improved in the treatment group. Patient-reported assessments of overall improvement also favored the active treatment.

Safety data were equally encouraging. No serious adverse events attributable to the drug emerged, and no participants discontinued due to tolerability issues—a critical finding for long-term therapy viability.

**Drug Mechanism and Development Path**

Losmapimod functions as a selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor. Fulcrum Therapeutics acquired exclusive rights from GSK after research identified p38α/β inhibition as a mechanism to suppress aberrant DUX4 expression, the underlying molecular driver of FSHD. Prior to this muscle dystrophy indication, losmapimod had been studied in over 3,600 subjects across various conditions without identified safety concerns.

**Disease Context**

FSHD represents one of the most prevalent muscular dystrophy subtypes, affecting approximately 30,000 individuals in the United States alone. The progressive muscle weakness and fat accumulation characteristically involve the facial muscles, shoulders, upper extremities, and lower limbs, ultimately compromising activities of daily living and mobility. Currently, no disease-modifying therapies have received FDA approval for FSHD.

**Regulatory Status and Next Steps**

The FDA has granted losmapimod both Fast Track designation and Orphan Drug Designation for FSHD treatment. These designations reflect the significant unmet medical need in this patient population. Fulcrum Therapeutics advanced the compound into Phase 3 evaluation through the REACH trial, which enrolled participants across the United States, Canada, and Europe. The company completed enrollment in September 2023 and expects to release topline Phase 3 data during the fourth quarter of 2024.

**Clinical and Commercial Implications**

Patrick Horn, M.D., Ph.D., Chief Medical Officer at Fulcrum Therapeutics, emphasized that the Phase 2b findings directly shaped the Phase 3 trial design and endpoint selection. The company remains positioned to pursue New Drug Application submission and commercialization upon successful Phase 3 outcomes, representing a potential therapeutic advance for the FSHD community.