Abstract Details

Title Design of REACH: Phase 3 Randomized, Double-Blind, Placebo-Controlled, 48-Week Study of the Efficacy and Safety of Losmapimod in FSHD

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P6 - Poster Session 6 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-007

Objective

Evaluate the efficacy and safety of losmapimod for the treatment of FSHD.

Background

FSHD is a chronic, variably progressive disease leading to accumulation of disability over decades. Nonclinical studies have shown that losmapimod (a small molecule p38 α/β MAPK inhibitor) reduces the aberrant expression of DUX4, the underlying cause of FSHD. Two Phase 2 clinical studies, a 48-week randomized controlled study (ReDUX4, FIS-002-2019) and a 52-week open-label study (OLS, FIS-001-2019) demonstrated evidence of benefit of treatment with losmapimod on muscle structure and function, as well as FSHD-relevant clinical endpoints that are recognized by patients and favorable safety and tolerability, supporting continued development. Fulcrum is initiating a Phase 3 double-blind, placebo-controlled trial to support the development of losmapimod in FSHD.

Design/Methods Approximately 230 people with FSHD, 210 with genetically confirmed FSHD1 and 20 with FSHD2, will be randomized 1:1 to receive losmapimod or placebo orally, twice daily for 48-weeks. The primary endpoint is reachable workspace quantification of total relative surface area (Q1-Q5) with 500 g wrist weight in the dominant arm, with secondary efficacy endpoints of quality of life in the neurological disorders upper extremity scale (Neuro-QoL UE), patient global impression of change (PGIC), and muscle fat infiltration (MFI) using whole-body musculoskeletal MRI (WB-MSK MRI). Exploratory assessments include muscle fat fraction, muscle strength by hand-held dynamometry, and patient reported outcomes (PRO) including patient global impression of severity (PGIS), a novel FSHD PRO, numeric pain rating scale (NPRS), 5-level EQ-5D (EQ-5D-5L) and healthcare utilization questionnaire.

Results The design of this Phase 3 study will be presented.

Conclusions The design of this Phase 3 study will be presented.

Authors/Disclosures
Marie-Helene Jouvin (Fulcrum Therapeutics) PRESENTER	Marie-Helene Jouvin has received personal compensation for serving as an employee of Fulcrum Therapeutics. Marie-Helene Jouvin has received personal compensation for serving as an employee of Pharvaris. Marie-Helene Jouvin has stock in Fulcrum Therapeutics. Marie-Helene Jouvin has stock in Pharvaris.
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.
	No disclosure on file
Leo H. Wang, MD, PhD, FAAN (University of Washington)	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 $5,000-$9,999 for serving as a Consultant for Avidity. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lupin. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Wang has received personal compensation in the range of $10,000-$49,999 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.
John Vissing, MD (Rigshospitalet)	Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne Therapeutics. Prof. Vissing has received personal compensation in the range of $0-$499 for serving as a Consultant for Denali Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Italfarmaco. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NMD Pharma. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Prof. Vissing has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sarepta. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Johnson & Johnson (Janssen). Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Edgewise Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. The institution of Prof. Vissing has received research support from Rigshospitalet. The institution of Prof. Vissing has received research support from Avidity. The institution of Prof. Vissing has received research support from Sanofi. The institution of Prof. Vissing has received research support from Roche. The institution of Prof. Vissing has received research support from AnnJi.
Jeffrey Statland, MD (University of Kansas Medical Center)	Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ML Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epic Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Armatus . Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kate Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vita Therapeutics. Dr. Statland has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity . Dr. Statland 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. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex . The institution of Dr. Statland has received research support from NIH. The institution of Dr. Statland has received research support from FSHD Society. The institution of Dr. Statland has received research support from Friends of FSH Research. The institution of Dr. Statland has received research support from FSHD Canada. The institution of Dr. Statland has received research support from MDA.
Jennifer Shoskes, PharmD (PepGen Inc)	No disclosure on file
John Jiang	No disclosure on file

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