NMD Pharma reported additional Phase IIa data for ignaseclant in Charcot-Marie-Tooth disease (CMT) at the 2026 Peripheral Nerve Society Annual Meeting, highlighting improvements in hand grip strength and motor function measures despite the study missing its primary endpoint earlier this year.
The SYNAPSE-CMT trial (NCT06482437) is a randomized, double-blind, placebo-controlled Phase IIa study evaluating ignaseclant, a first-in-class oral inhibitor of the skeletal muscle chloride channel ClC-1, in 81 adults with genetically confirmed CMT type 1 or type 2. Participants received treatment for 21 days followed by a seven-day observation period.
NMD Pharma disclosed in February that the study failed to meet its primary endpoint, improvement in the 6-minute walk test at day 21. Data presented at PNS 2026 focused on secondary and exploratory measures that may help guide future development.
According to the company, hand grip strength improved significantly versus placebo at both day 21 (p=0.02) and day 28 (p<0.01). Improvements were also observed in the CMT Functional Outcome Measure composite score, with statistically significant differences reported at day 28. Positive trends were reported in the 9-hole peg test and the 10-meter walk/run assessment.
One of the more notable findings was the persistence of benefit after treatment cessation. Functional improvements remained evident seven days after the final dose, suggesting the effects of ClC-1 modulation may extend beyond immediate pharmacological enhancement of muscle excitability. The mechanism underlying this observation remains uncertain and will require further investigation.
The safety profile was favorable. All adverse events were mild or moderate, with no serious adverse events or treatment discontinuations reported.