NMD Pharma A/S has initiated a Phase 2a clinical trial (SYNAPSE-CMT) to evaluate NMD670, a novel treatment for Charcot-Marie-Tooth disease (CMT) types 1 and 2. The first patient was dosed at the Austin Neuromuscular Center in Austin, TX, under the direction of Yessar Hussain, MD, following FDA IND clearance in June 2024. This study marks a significant step forward in addressing the unmet needs of CMT patients, for whom there are currently no approved disease-modifying therapies.
NMD670: A Novel Approach to Neuromuscular Dysfunction
NMD670 is a first-in-class small molecule inhibitor targeting the skeletal muscle-specific chloride ion channel 1 (ClC-1). Preclinical and early clinical data suggest that inhibiting ClC-1 can amplify the muscle's responsiveness to weak signals, thereby improving neuromuscular transmission and restoring skeletal muscle function. This mechanism of action is particularly relevant in CMT, where impaired neuromuscular function contributes to muscle weakness and fatigue.
SYNAPSE-CMT Trial Design
The Phase 2a clinical trial (NCT06482437) is a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of NMD670. Eighty adult patients with genetically confirmed CMT1 or CMT2 subtypes will receive a twice-daily oral dose of NMD670 or placebo over 21 days. The trial's primary endpoints include changes in the 6-minute walk test (6MWT), time to complete the 10-meter walk/run test (10MW/R), and time to complete the timed-up-and-go test (TUG). Secondary endpoints will assess other measures of muscle function, safety, and tolerability.
Clinical Significance and Unmet Need
CMT is a group of hereditary sensory and motor neuropathies affecting approximately 136,000 individuals in the United States and 3.2 million worldwide. The disease causes progressive damage to peripheral nerves, leading to muscle weakness, fatigue, and atrophy. As Yessar Hussain, MD, from Austin Neurological Center, noted, "Patients with CMT are very excited about entering into this study... This is the only clinical study with a clinically feasible treatment to address the muscle weakness and fatigue with a pharmaceutical therapy at the moment."
Broader Clinical Program
The initiation of the SYNAPSE-CMT trial expands NMD Pharma's clinical program for NMD670, which includes ongoing Phase 2 studies in spinal muscular atrophy (SMA) type 3 and generalized myasthenia gravis (gMG). NMD670 has also received orphan-drug designation from the U.S. FDA for the treatment of gMG, highlighting its potential in addressing rare neuromuscular disorders.
