Abstract Details

Title Annualized Rates of Change from A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 48-Week Study of Losmapimod in Subjects with FSHD: ReDUX4

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S48 - Therapeutics for Muscle Disease (5:18 PM-5:30 PM)

Poster/Presentation
Number 010

Objective Evaluate annualized clinical outcome changes in subjects with facioscapulohumeral muscular dystrophy (FSHD) treated with losmapimod compared with placebo.

Background FSHD is a relentless, variably progressive disease leading to accumulation of disability over decades. Fulcrum is developing losmapimod, a small molecule p38 α/β MAPK inhibitor, to treat FSHD. An annualized analysis provides data on the slope of disease progression and the potential for treatment with losmapimod to change that slope over time.

Design/Methods Subjects aged 18-65 years with FSHD1, CSS 2-4, and MRI-eligible muscles for biopsy were randomized 1:1; losmapimod (15 mg BID): placebo. Assessments included for analysis: MRI assessments of muscle health, reachable workspace (RWS), dynamometry and TUG. Annualized rate of change (%/yr) was calculated using a linear mixed-effects model to estimate slope and percent change per year. Annualized analysis of RWS (measured in Reachable Surface Area, RSA) was prespecified; all other analyses are post-hoc.

Results

Eighty subjects (N=40/group), mean age 45.7 (±12.5) years, Ricci score 3.2 were enrolled. Annualized rate of change (%/yr) in total RSA for losmapimod vs. placebo dominant arm: -0.44 vs. -8.42; p=0.07; non-dominant arm: 4.88 vs. -4.02; p=0.01. This slowing or improvement is supported by structural measures via MRI and functional outcomes (dynamometry and TUG). MRI annualized rates of change for losmapimod vs. placebo were 0.31 vs 3.82 for MFI, 4.42 vs 5.96 for MFF, and -7.15 vs -4.50 for LMV. Maximum dynamometry in the shoulder abductors showed variability in annualized rate of change for losmapimod vs. placebo (L -1.98 vs 13.62; R -14.39 vs -8.49) and in hand grip (L -8.30 vs -13.44; R -13.95 vs -15.27). In TUG, the annualized rate of change was -0.93 vs 2.23% in the losmapimod vs placebo group.

Conclusions Annualized rates of change in clinical outcomes support disease slowing or improvement in losmapimod treated subjects compared to placebo.

Authors/Disclosures
Olga Mitelman, MD (Fulcrum Therapeutics) PRESENTER	Dr. Mitelman has received personal compensation for serving as an employee of Fulcrum Therapeutics. Dr. Mitelman has stock in Fulcrum Therapeutics.
Alrabi Tawil, MD, FAAN (University of Rochester Medical Center)	Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kate Therapeutics. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for meRicule. The institution of Dr. Tawil has received research support from Friends of FSH Research. The institution of Dr. Tawil has received research support from FSH Society. The institution of Dr. Tawil has received research support from NIH. The institution of Dr. Tawil has received research support from Fulcrum. Dr. Tawil has received intellectual property interests from a discovery or technology relating to health care.

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