Losmapimod Phase 2b Trial Results for FSHD Published in The Lancet Neurology

Fulcrum Therapeutics, a biopharmaceutical firm dedicated to treating rare genetic diseases, has reported findings from their Phase 2b clinical trial for losmapimod, a drug intended to treat facioscapulopumeral muscular dystrophy (FSHD). The study's outcomes have been made public in The Lancet Neurology, a respected peer-reviewed medical journal.
FSHD is a severe and uncommon condition that progressively weakens muscles, primarily affecting the face, shoulders, upper arms, abdomen, and lower limbs due to abnormal DUX4 protein expression. Currently, no treatments are available to modify the disease's progression.
Patrick Horn, Fulcrum's chief medical officer, highlighted the significance of the study's publication, stating that it not only validated losmapimod's therapeutic potential but also influenced the design and efficacy endpoints for their Phase 3 clinical trial. The company anticipates releasing key data from the REACH trial in the fourth quarter of 2024, which could significantly impact the FSHD patient community.
Despite the primary endpoint of the study, which measured changes in DUX4-driven gene expression in muscle samples, not showing significant differences between the treated and placebo groups, losmapimod demonstrated positive effects on muscle structure and function. Improvements were observed in muscle fat infiltration and shoulder girdle functionality, as well as in patients' self-reported assessments of their condition. The drug was also well-tolerated, with no serious adverse events or treatment discontinuations due to side effects.
The Phase 3 clinical trial for losmapimod, which concluded enrollment in September 2023, is expected to deliver its topline data in Q4 2024. The Phase 2b ReDUX4 trial involved 80 participants aged 18 to 65 with FSHD type 1, who were given losmapimod or a placebo over 48 weeks.
Losmapimod, a selective p38α/β MAPK inhibitor, was in-licensed from GSK after its potential in reducing DUX4 expression was identified. It has shown promise in slowing disease progression and improving upper limb function for FSHD patients. The drug has been granted Fast Track and Orphan Drug Designations by the FDA for FSHD treatment.
FSHD is a debilitating disease that leads to the loss of daily living capabilities due to muscle atrophy and chronic pain. It is one of the most prevalent forms of muscular dystrophy, with an estimated 30,000 patients in the United States.
Fulcrum Therapeutics is focused on developing treatments for genetically defined rare diseases with significant unmet medical needs. Their lead programs include losmapimod for FSHD and pociredir for sickle cell disease and other hemoglobinopathies. The company's FulcrumSeek™ platform identifies drug targets that can correct gene expression to address the root cause of genetic mis-expression.

About Fulcrum Therapeutics:
Fulcrum Therapeutics is a clinical-stage biopharmaceutical company that aims to enhance the lives of patients with genetically defined rare diseases, particularly in areas where medical needs are high. The company's leading programs in development are losmapimod for FSHD and another drug, pociredir, intended to increase fetal hemoglobin expression for the treatment of sickle cell disease and related conditions. Fulcrum utilizes its proprietary FulcrumSeek™ technology to identify drug targets that can modulate gene expression to treat the underlying causes of genetic mis-expression.