Assess clinical efficacy of losmapimod to slow or stop disease progression with Reachable Workspace (RWS).
RWS is a 3D assessment of function that measures upper extremity mobility. Fulcrum is developing losmapimod, a small molecule inhibitor of p38 ?/? MAPK, to treat FSHD.
ReDUX4 is a placebo-controlled study assessing 80 subjects aged 18 to 65 years with genetically confirmed FSHD1, clinical severity score 2 to 4 (range 0-5) randomized 1:1 to 15 mg losmapimod or placebo PO twice daily for 48 weeks. Open-label study (OLS) is a single-site study evaluating efficacy of losmapimod for 52 weeks in 14 subjects with same inclusion criteria. RWS was performed with and without 500 g wrist weights in the dominant (D) and non-dominant (ND) arm at baseline and at individual timepoints through end of study. Quantitative assessment includes total relative surface area (RSA) composed of 5 quintants Q1-Q5 measured on a 0-1.25 scale representing frontal and posterior inferior reachable area with each quintant measuring 0.25.
In ReDUX4, losmapimod resulted in significant clinical improvements in total RSA, losmapimod vs. placebo D: 0.019 vs. -0.048; difference 0.067; p=0.01; ND: 0.021 vs. -0.024, difference 0.045; p<0.05. Placebo subjects lost 2.6-3.6% total RSA without weights and 1.9-3.8% with weights. In OLS, improvements were measured bilaterally; range 0.03-0.04. In ReDUX4, annualized rate of change (%) in total RSA in losmapimod vs. placebo D: -0.44 vs. -8.42; p=0.07; ND: 4.88 vs. -4.02; p=0.01 and in OLS range 3.28-5.68. RSA by domain showed that the losmapimod arm had either improvements or no worsening, particularly in Q1 and Q3 (above shoulder), and Q5 (posterior inferior).
Conclusions: RWS is a clinically meaningful upper extremity assessment of function that can be used to assess disease progression and treatment efficacy accurately. RWS demonstrated that losmapimod significantly preserves or improves function.