Fulcrum Therapeutics Inc. (FULC) experienced a significant drop in its stock price on Thursday following the release of disappointing data from the Phase 3 REACH trial evaluating losmapimod in patients with Facioscapulohumeral Muscular Dystrophy (FSHD). The study failed to achieve its primary endpoint, which was to demonstrate a change from baseline in relative surface area (RSA) with losmapimod compared to placebo. This outcome is particularly discouraging as it contradicts the positive results observed in the earlier Phase 2 ReDUX4 trial.
Secondary endpoints in the REACH trial also failed to reach nominal statistical significance. While losmapimod’s safety and tolerability profile remained consistent with previous studies, the lack of efficacy on both primary and secondary endpoints has prompted Fulcrum to suspend the losmapimod program for FSHD. The company will thoroughly analyze the data received this week and present its findings at an upcoming medical meeting.
Specifically, participants receiving losmapimod showed a minimal 0.013 improvement in RSA at week 48 compared to placebo patients, who exhibited a 0.010 improvement. This difference was statistically insignificant (p-value = 0.75). RSA is a crucial outcome measure used to monitor disease progression in neuromuscular disorders affecting the upper extremities.
Similarly, the study demonstrated a slight increase in Muscle Fat Infiltration (an indicator of muscle quality) at week 48 for those on losmapimod (0.42%) compared to the placebo group (0.576%). However, this difference was not statistically significant (p-value = 0.16). In terms of abductor strength, participants receiving losmapimod showed a 9.63% improvement at week 48, compared to a 2.24% improvement in the placebo arm (p-value = 0.51).
The rate of treatment-related adverse events was comparable in both treatment arms, and there were no serious adverse events reported among participants receiving losmapimod. Despite the promising initial findings from the Phase 2 trial, the lack of replication in the Phase 3 REACH trial has led Fulcrum to make a difficult decision. The company will now focus its resources on advancing other promising therapies in its pipeline, including pociredir for sickle cell disease and novel agents for Diamond-Blackfan Anemia.
