P.137 Reachable workspace to evaluate efficacy of losmapimod in subjects with FSHD in two phase 2 studies

• Published in: Neuromuscular disorders : NMD Vol. 32; p. S104
• Main Author: Tawil, R.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2022
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2022.07.259

Assess 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 (LOS; a small molecule inhibitor of p38 α/β MAPK) to treat FSHD. Eighty subjects (N=40/group) age 18-65 yrs with FSHD1, CSS 2-4, were randomized 1:1 LOS 15 mg BID: placebo (PBO) in ReDUX4.Single-site open-label study (OLS) evaluated efficacy in 14 subjects on LOS for 52 weeks with same inclusion. RWS was performed with and without 500g wrist weights in dominant (D) and non-dominant (ND) arm. Assessment includes total relative surface area (RSA) of 5 domains measured on a 0-1.25 scale representing frontal and posterior inferior reachable area, each domain measuring .25. In ReDUX4, LOS resulted in significant clinical improvements in total RSA, LOS vs PBO D: 0.019 vs -0.048; dif 0.067 p=0.01; ND: 0.021 vs -0.024, dif 0.045 p<0.05. PBO 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, total RSA annualized rate of change (%) in LOS vs. PBO D: -0.44 vs -8.42; p=0.07; ND: 4.88 vs -4.02; p=0.01 and OLS range 3.28-5.68.RSA by domain showed improvements/no worsening in LOS, particularly in Q1 and Q3 (above shoulder) and Q5 (posterior inferior). 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 LOS significantly preserves or improves function.