Results from 96 Weeks Open-Label Extension of a Phase 2 Trial of Losmapimod in Subjects with FSHD: ReDUX4 (S48.008)

Abstract

<h3>Objective:</h3> Evaluate the 96-week results from the open-label extension of a Phase 2 trial of losmapimod in subjects with FSHD. <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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 2^nd 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 adverse events were fall (22.4%), headache (14.5%), arthralgia (7.9%), and back pain (7.9%). <h3>Conclusions:</h3> Losmapimod slowed disease progression and demonstrated maintenance of effect for through a 96-week period, with no new safety findings. <b>Disclosure:</b> Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AskBio. Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fulcrum Therapeutics. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Wang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Wang has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. The institution of Dr. Wang has received research support from National Institute of Health. Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with US Government. Dr. Han has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fulcrum. Dr. Han has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Han has received research support from Fulcrum. Dr. Shoskes has received personal compensation for serving as an employee of Fulcrum Therapeutics. An immediate family member of Dr. Shoskes has received personal compensation for serving as an employee of Exact Science. Dr. Jiang has received personal compensation for serving as an employee of Fulcrum Therapeutics. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for DYNE Therapeutics. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead Pharma. Dr. Tawil has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum Therapeutics. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acceleron Pharma. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MT Pharma. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharma. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for miRecule. 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. Dr. Tawil has received publishing royalties from a publication relating to health care.