NMD670 granted orphan drug status for CMT as clinical trial starts
Phase 2 study seeks 80 participants in US, Europe
The U.S. Food and Drug Administration (FDA) has granted orphan drug status to investigational oral therapy NMD670 to treat Charcot-Marie-Tooth disease (CMT).
Orphan drug designation is given to therapies designed to prevent, diagnose, or treat rare diseases, defined as one affecting fewer than 200,000 people in the U.S. The designation is intended to accelerate development of such therapies by providing incentives such as tax credits for clinical trials, exemptions from certain fees, and seven years of market exclusivity should the therapy eventually be approved.
Meanwhile, the first clinical trial (NCT06482437) testing NMD670 in people with CMT is underway and seeking participants. The FDA cleared the trial last June, and developer NMD Pharma announced in November that the study had been initiated and a first patient dosed.
Called SYNAPSE-CMT, the Phase 2 study will recruit 80 adults with genetically confirmed CMT type 1 and type 2 — the most common forms of the disease — at sites in the U.S. and Europe.
“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,” Thomas Holm Pedersen, PhD, CEO of NMD Pharma, said in a company press release.
Small molecule aimed at inhibiting CIC-1
CMT is a group of inherited neuromuscular disorders characterized by peripheral neuropathy, or damage to the nerves outside the brain and spinal cord that are responsible for sensory perception and movement. Among its symptoms are weakness and wasting of the skeletal muscles, which control voluntary movements.
NMD670 is a first-in-class oral small molecule that inhibits chloride ion channel 1 (CIC-1), a protein involved in skeletal muscle function.
Data indicate that inhibiting CIC-1 boosts signaling at the neuromuscular junction (NMJ) – the site where nerve and muscle cells communicate to facilitate voluntary movements. NMD Pharma believes this will help restore more normal skeletal muscle function in neuromuscular diseases such as CMT.
The orphan drug 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,” Holm Pedersen said.
Last month, the company announced a publication in the Annals of Clinical and Translational Neurology containing data supporting the role of CIC-1 inhibition in CMT. It included findings from the observational ESTABLISH study (NCT04980807), which NMD Pharma launched in 2021 to learn more about how NMJ signaling is impacted in CMT. The study enrolled 21 people with CMT1 or CMT2 as well as 10 healthy people, all of whom underwent tests to evaluate their physical function and NMJ signaling.
Results showed that CMT patients had notable NMJ deficits compared with healthy people. Among patients, a higher degree of NMJ dysfunction correlated with worse physical function, including in measures of strength, balance, mobility, and endurance.
The publication also included preclinical findings from mouse models of CMT1 and CMT2. Data there showed that treatment with NMD670 led to improvements in aspects of muscle function, including maximum muscle force and endurance.
In SYNAPSE-CMT, participants will be randomly assigned to receive NMD670 or a placebo, taken twice daily as oral tablets for three weeks. The main goal is to evaluate changes in physical function, which will be assessed through tests including the six-minute walk, 10-meter walk/run, and timed-up-and-go tests.
Secondary outcomes include measures of disease severity, fatigue, neuropathy, life quality, and safety. It’s expected to finish in 2026.
Ongoing clinical trials are also testing NMD670 for other neuromuscular indications, including generalized myasthenia gravis (gMG), and spinal muscular atrophy. The FDA has granted NMD670 orphan drug status for gMG.
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