REACH, a phase III clinical trial of losmapimod, is initiated in facioscapulohumeral muscular dystrophy. - Fulcrum Therapeutics.

FSHD is a serious, rare, progressive and debilitating disease for which there are no approved treatments. It is characterized by fat infiltration of skeletal muscle leading to muscular atrophy involving the face, scapula and shoulders, upper arms, and abdomen. Impact on patients includes profound decreases in the ability to perform activities of daily living, loss of upper limb function, loss of mobility and independence, and chronic pain.

“There are no approved therapies for FSHD, and there is a clear and urgent need for a treatment to slow or stop disease progression,” said Nicholas Johnson, MD, M.Sci., FAAN, associate professor, division chief of neuromuscular, and vice chair of research in the department of neurology at Virginia Commonwealth University. “For people with FSHD, every day without a treatment is another day that they may lose strength, the ability to lift their arms, or walk unassisted. Losmapimod is the first and only investigational medicine in clinical development. The data to date are very promising, showing meaningful clinical benefit and a well-established safety and tolerability profile. I look forward to further investigating losmapimod in the REACH trial.”

Based on results from a Phase IIb study of losmapimod showing clinical benefit, Fulcrum engaged with U.S. and EU regulatory agencies, including the FDA, and gained alignment on key aspects of the design for a Phase III trial. REACH will be a randomized, double-blind, placebo-controlled, multi-national trial to evaluate the efficacy and safety of losmapimod for the treatment of FSHD. The trial is expected to enroll approximately 230 adults with FSHD. Patients will be randomized 1:1 to receive either losmapimod, administered orally as a 15 mg tablet twice a day, or placebo, and evaluated over a 48-week treatment period. The primary endpoint of the study is the absolute change from baseline in Reachable Workspace (RWS). Secondary endpoints include muscle fat infiltration (MFI), Patient Global Impression of Change (PGIC), and Quality of Life in Neurological Disorders of the upper extremity (Neuro QoL UE). REACH will also include patient-centered assessments of healthcare utilization.

Judith A. Dunn, Ph.D., Fulcrum’s president of research and development, said, “We learned from our Phase IIb trial that RWS, MFI and patient-reported outcomes are reliable measures of disease progression and that we can observe meaningful differences in these endpoints compared to placebo after just 48 weeks of treatment with losmapimod. REACH is optimized to demonstrate similar statistically and clinically significant benefits and represents an important step in delivering a life-changing therapy to people with FSHD.”

Results from ReDUX4 : a randomized, double-blind, placebo-controlled Phase IIb trial, which enrolled approximately 80 patients treated for 48 weeks, demonstrated clinically relevant benefits on multiple measures of muscle health and function as well as patient-reported outcomes. Notably, losmapimod improved accessible surface area in RWS, a quantitative measure of upper extremity range of motion and function that has shown to correlate with the ability to independently perform activities of daily living. Losmapimod also decreased progression of fat infiltration in muscles already affected by disease and preserved the health of normal-appearing muscles.

Additionally, losmapimod-treated patients reported feeling better compared to those on placebo using the assessment. Consistent with losmapimod’s extensive safety and tolerability profile from clinical trials outside of FSHD, there were no serious treatment-related adverse events observed in the Phase IIb trial.