Objective: Evaluate the 96-week results from the open-label extension of a Phase 2 trial of losmapimod in subjects with FSHD.
Background: Facioscapulohumeral muscular dystrophy (FSHD) is a relentless, variably progressive disease leading to accumulation of disability. Fulcrum is developing losmapimod, a small molecule p38 α/β MAPK inhibitor, to treat FSHD.
Methods/Design: ReDUX4 is a 48-week, placebo-controlled study assessing 80 subjects, 18-65 years old with genetically confirmed FSHD1, Ricci score 2-4, randomized 1:1 to receive 15 mg losmapimod or placebo (PO BID), followed by an Open-Label Extension (OLE) with all participants receiving losmapimod.
Results: Seventy-six of 77 (99%) participants entered the OLE after 48 weeks, and 74 (97%) were enrolled at Week 96. For participants continuing to receive losmapimod (LOS/LOS), durability of treatment response was observed at 96 weeks, by assessing upper extremity function with Reachable Workspace (RWS). Placebo participants who converted to losmapimod (PBO/LOS) at Week 48 demonstrated trends of slowing or stopping disease progression based on RWS. Annualized total (Q1-5) relative surface area (RSA) in the dominant arm with weights demonstrated stability in the LOS/LOS group during the 2nd year of dosing compared to the first (0.18%/yr vs -0.77%/yr, respectively) and improvement in PBO/LOS (4.07% vs -9.96%). Mean change in RSA from Week 48 to Week 96 was 0.0 for LOS/LOS and 0.02 for PBO/LOS with similar findings in the non-dominant arm in both groups and without weight. No related serious adverse events or discontinuations due to adverse events were reported in 96 weeks of dosing. Most commonly reported AEs were fall (22.4%), headache (14.5%), arthralgia (7.9%), and back pain (7.9%).
Conclusions: Losmapimod slowed disease progression and demonstrated maintenance of effect through a 96-week period, with no new safety findings.