NMD Pharma Ignaseclant Phase 2a CMT Trial Shows Muscle Strength Benefits

NMD Pharma presented data from its Phase 2a SYNAPSE-CMT trial showing that the oral drug ignaseclant improved muscle strength and motor function in adults with Charcot-Marie-Tooth disease, with benefits sustained seven days after treatment cessation. The findings were presented in a late-breaking oral presentation at the 2026 Peripheral Neuroscience Association Annual Meeting.

The randomized, double-blind, placebo-controlled study (NCT06482437) enrolled 81 ambulatory adult patients with genetically confirmed CMT type 1 or type 2 across clinical sites in the US and Europe. Participants received twice-daily oral ignaseclant or placebo for 21 days, with a follow-up assessment at day 28. Results demonstrated consistent signals of benefit across multiple secondary functional endpoints. Improvements versus placebo were observed in the CMT Functional Outcome Measure composite scale at Day 7, with continued improvements to Day 21 and significant gains sustained at Day 28. Hand grip strength showed significant gains at Day 21 (p=0.02) and Day 28 (p<0.01). Additional improvement trends were seen in the 9-hole peg test, with positive trends in lower limb outcomes such as the 10-meter walk/run test.

Ignaseclant was well tolerated, with all adverse events reported as mild or moderate and no serious adverse events or discontinuations. The findings indicate that 21 days of ClC-1 inhibition with ignaseclant improved muscle strength and motor function in adults with CMT, with effects persisting seven days after treatment cessation, suggesting potential functional or structural recovery at the neuromuscular junction.

The trial's primary endpoint, the six-minute walk test, was not met, but the company noted that this test may not be the most sensitive measure to capture change in a short CMT study. Participants also reported improvements in physical function and disease impact as assessed by the CMT Health Index.

Ignaseclant, previously known as NMD670, is a first-in-class skeletal muscle-targeted therapy that inhibits the ClC-1 chloride channel, a protein found in muscle cells that normally prevents unwanted muscle activation. By inhibiting this channel, the drug makes muscle cells more responsive to input from weaker nerve signals, helping with muscle activation and improving strength and function. This mechanism makes ignaseclant a candidate for all CMT types, independent of specific disease-causing mutations.

Last year, ignaseclant received orphan drug designation from the U.S. Food and Drug Administration for the treatment of CMT. NMD Pharma plans to present full results at a scientific meeting later this year and will discuss next steps with regulatory authorities in the U.S. and Europe, including the design of a pivotal trial intended to support approval of regulatory applications. The company has already started producing the drug at a larger scale to support a longer clinical trial.