MANOEUVRE Study Design: A Study of GYM329 (RO7204239) in Patients with Facioscapulohumeral Muscular Dystrophy (FSHD) (S2.010)

Objective:

To assess the pharmacodynamics (PD), safety, tolerability, pharmacokinetics (PK) and efficacy of GYM329 in ambulant adult patients with FSHD.

Background:

FSHD is a genetic muscle disorder characterized by asymmetric skeletal muscle weakness and muscle atrophy. Time of first symptom onset is variable, from childhood to adulthood, but typically manifests in the second or third decade of life. There is no approved therapy for FSHD; thus, there is a high unmet medical need as the disease can cause significant morbidity and reduce the quality of life of affected patients.

Design/Methods:

GYM329 (RO7204239) is an investigational, recycling and antigen-sweeping monoclonal anti-myostatin antibody. MANOEUVRE (NCT05548556) is a Phase 2, multicenter, randomized, placebo-controlled, double-blind study that will investigate the effect of GYM329 in adult ambulant patients with a genetically confirmed diagnosis of FSHD1 or FSHD2. Participants (target enrollment N~48) will complete a pre-treatment period to collect baseline movement data via a wearable device before randomization (1:1, GYM329: placebo) for the 52-week double-blind treatment period. GYM329 or placebo will be administered every 4 weeks by subcutaneous injection.

Results:

The primary endpoints are the percentage change from baseline in the contractile muscle volume of quadriceps femoris muscle as assessed by magnetic resonance imaging (MRI) at Week 52 and the safety of GYM329. Secondary endpoints include the change from baseline of muscle volume in various muscles and groups of muscles as assessed by MRI. Exploratory efficacy endpoints include assessment of motor function and strength. The MANOEUVRE study design will be presented.

Conclusions:

This study will provide valuable information about the PD, safety, PK and efficacy of GYM329 treatment in patients with FSHD. Disclosure: 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 MT Pharma. 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 $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. 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. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fulcrum. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avidity. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for DyneTherapeutic. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Ms. Eichinger has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for FSHD Society. The institution of Ms. Eichinger has received research support from Charcot Marie Tooth Association. The institution of Dr. Morrow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Morrow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Morrow has received research support from Muscular Dystrophy Association. Dr. Tasca has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Tasca has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ipsen Pharma. Dr. Tasca has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. 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 Fulcrum Therapeutics. 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 as a Consultant for Amicus therapeutics. Prof. Vissing has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sarepta. 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 Pfizer. 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 UCB Biopharma. 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 Arvinas ML Biopharma. The institution of Prof. Vissing has received research support from Rigshospitalet. The institution of Prof. Vissing has received research support from UCB Pharma. The institution of Prof. Vissing has received research support from Sanofi. The institution of Prof. Vissing has received research support from NOVO Foundation. Angela Dodman has received personal compensation for serving as an employee of F. Hoffman-La Roche Ltd. Birgit Jaber has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Birgit Jaber has received stock or an ownership interest from F. Hoffmann-La Roche Ltd. Birgit Jaber has received personal compensation in the range of $100,000-$499,999 for serving as a Senior Safety Director with F. Hoffmann-La Roche Ltd. Heidemarie Kletzl has received personal compensation for serving as an employee of Hoffmann-La Roche. Tammy McIver has received personal compensation for serving as an employee of Roche. Tammy McIver has received stock or an ownership interest from Roche . Renata SCALCO has received personal compensation for serving as an employee of Roche. Renata SCALCO has received stock or an ownership interest from Roche. Wai Yin Yeung has nothing to disclose. Dr. Gaki has received personal compensation for serving as an employee of Roche. Dr. Gaki has received stock or an ownership interest from Roche Products Ltd. Dr. Wagner has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Dr. Wagner has stock in F. Hoffmann-La Roche.