NMD Pharma A/S, a clinical-stage biotech company, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to NMD670 for the treatment of Charcot-Marie-Tooth disease (CMT). NMD670 is a novel, oral, small molecule inhibitor of the skeletal muscle-specific chloride ion channel ClC-1.
CMT is a group of hereditary neuropathies characterized by muscle weakness, fatigue, and sensory deficits. It affects an estimated 136,000 individuals in the US and over 3 million worldwide. Currently, there are no approved therapies for CMT, highlighting a significant unmet medical need.
Clinical Development of NMD670
NMD670 is currently being evaluated in a Phase 2 clinical trial (SYNAPSE-CMT) involving 80 adult patients with genetically confirmed CMT1 or CMT2 subtypes across clinical sites in the U.S. and Europe. The trial, initiated in November 2024, is assessing a twice-daily oral dose of NMD670 over 21 days (NCT06482437).
Thomas Holm Pedersen, Chief Executive Officer of NMD Pharma, stated, "NMD Pharma is committed to addressing the need of patients living with neuromuscular diseases such as CMT, and we are thrilled that the FDA has granted orphan drug designation to NMD670. Based on positive results from preclinical studies and the recently published ESTABLISH1 CMT observational study, this designation not only highlights the urgent need for novel, effective treatments for this rare disease, but also underscores the therapeutic potential of our skeletal muscle-specific ClC-1 inhibitor approach to address the associated muscle weakness and fatigue."
Mechanism of Action
NMD670 is a first-in-class small molecule designed to inhibit the skeletal muscle-specific chloride ion channel 1 (ClC-1). Preclinical data suggest that ClC-1 inhibition amplifies the muscle's responsiveness to weak signals, improving neuromuscular transmission and restoring skeletal muscle function. This mechanism has shown clinical evidence of efficacy in myasthenia gravis and preclinical promise in spinal muscular atrophy and sarcopenia.
Significance of Orphan Drug Designation
The FDA's Orphan Drug Designation provides orphan status to therapies intended for the prevention, diagnosis, or treatment of diseases affecting fewer than 200,000 people in the US. This designation offers several benefits, including tax credits for clinical trials, exemptions from certain FDA fees, and seven years of market exclusivity upon approval.
Ongoing Clinical Trials
NMD Pharma has three ongoing global clinical trials investigating NMD670 across rare neuromuscular diseases. These include a Phase 2 study in adults with spinal muscular atrophy (SMA) type 3, a Phase 2b study in generalized myasthenia gravis (gMG) patients, and the Phase 2 CMT study. Data readouts from these trials are expected from 2H/2025 through 1H/2026.
