Phase 2a Study of Ignaseclant Suggests Strength and Functional Benefits in Charcot-Marie-Tooth Disease

New findings from the phase 2a SYNAPSE-CMT trial (NCT06482437) showed that ignaseclant (NMD Pharma), an investigational skeletal muscle chloride channel inhibitor, did not meet its primary end point, measured by the 6-minute walk test (6MWT), in adults with Charcot-Marie-Tooth disease (CMT). Despite this, treatment with the agent was associated with improvements in muscle strength and motor function after 21 days.^1,2

Although researchers did not observe any treatment effect in the 6MWT among 81 participants, findings showed an improvement trend relative to placebo on the Charcot-Marie-Tooth Functional Outcome Measure (CMT-FOM) at both day 21 and day 28 (P = .06). Presented at the 2026 Peripheral Nerve Society (PNS) Annual Meeting, held June 13-16, in Maastricht, The Netherlands, by Vera Kiyasova, MD, PhD, clinical development director at NMD pharma, participants were randomly assigned to receive ignaseclant 400 mg twice daily or placebo for 21 days.

SYNAPSE-CMT was a randomized, double-blind, placebo-controlled phase 2a trial that investigated the efficacy and safety of ignaseclant, formerly NMD670, among ambulatory adults with CMT type 1 or CMT type 2. In the study, the end points included CMT-FOM, 10-meter walk/run, and patient-reported outcomes such as the CMT Health Index (CMT-HI), with the primary end point being the 6-minute walk test.

Coming into the study, participants had a mean baseline CMT-FOM score of 47.8 (SD, 5.76), a mean age of approximately 50 years, and were 52.5% women. Investigators reported that baseline characteristics were generally balanced between treatment groups, with approximately 67% of enrolled participants having CMT type 1 and 33% having CMT type 2.

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Handgrip strength improved as early as day 7 among participants receiving ignaseclant, with statistically significant differences observed by day 21 (P = .02) and day 28 (P <.01). Improvements were also reported on the 9-hole peg test, suggesting potential effects on upper extremity motor function and dexterity. In addition, lower-extremity assessments demonstrated numerical trends favoring ignaseclant.

Patient-reported outcomes similarly favored active treatment. Using the CMT-HI, investigators reported that 53% of participants treated with ignaseclant achieved a clinically meaningful improvement, defined as a decrease of more than 3.2 points, compared with 37% of those receiving placebo at day 21. According to the investigators, treatment effects appeared generally consistent across disease subtypes and other predefined subgroups.

All adverse events on ignaseclant were mild or moderate, with no serious adverse events or study discontinuations. Notably, some functional improvements persisted through day 28, 7 days after treatment discontinuation. Researchers suggested that this observation may warrant further investigation into whether ClC-1 inhibition could influence neuromuscular function beyond the active treatment period.

Ignaseclant has previously been evaluated in a randomized, double-blind, placebo-controlled, 3-way crossover phase 2a study that assessed 2 single oral doses of the agent versus placebo in 12 patients with symptomatic generalized myasthenia gravis. Findings from the study, published in Science Translational Medicine, demonstrated statistically significant improvements in Quantitative Myasthenia Gravis total scores compared with placebo, with no major safety concerns reported.³ In January 2025, the FDA granted orphan drug designation to ignaseclant for the treatment of CMT disease.⁴

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REFERENCES
1. Herrmann D, Claeys K, Andersen H, et al. Efficacy and Safety of Ignaseclant in CMT: A Phase 2a Study. Presented at: 2026 Peripheral Nerve Society (PNS) Annual Meeting; June 13-16; Maastricht, The Netherlands. 0633.
2. NMD Pharma announces topline results from its Phase 2a study of ignaseclant in Charcot-Marie-Tooth disease Types 1 and 2. News release. NMD Pharma. February 3, 2026. Accessed June 12,2026. https://www.nmdpharma.com/news/topline-results
3. NMD Pharma Publishes Comprehensive Data Package for NMD670 in Science Translational Medicine. News release. NMD Pharma. March 21, 2024. Accessed June 12, 2026. https://www.nmdpharma.com/news/comprehensive-data-package-for-nmd670-in-science-translational-medicine
4. NMD Pharma Announces FDA Orphan Drug Designation Granted to NMD670 for the Treatment of Patients with Charcot-Marie-Tooth Disease. News release. NMD Pharma. January 6, 2025. Accessed June 12, 2026. https://www.nmdpharma.com/news/fda-orphan-drug-designation