NMD Pharma's ignaseclant shows muscle gains in Phase 2a CMT study

NMD Pharma has presented Phase 2a data showing its lead compound ignaseclant produced consistent functional improvements in adults with Charcot-Marie-Tooth disease, with effects maintained for at least a week after dosing stopped. The results, from the SYNAPSE-CMT study, were delivered in a late-breaking oral session at the 2026 Peripheral Neuroscience Association Annual Meeting in Maastricht on 14 June by David Herrmann, Chief of the Neuromuscular Division at the University of Rochester Medical Center.

The randomised, double-blind, placebo-controlled trial enrolled 81 ambulatory adults with genetically confirmed CMT type 1 or 2 across sites in the US and Europe. Participants received twice-daily oral ignaseclant for 21 days, with follow-up assessments at day 28.

Trial readouts

On the primary activity signal, improvement versus placebo was observed on the CMT Functional Outcome Measure composite scale from day 7 onwards, with gains sustained and statistically significant at day 28. Hand grip strength showed a similar trajectory, reaching significance at day 21 (p=0.02) and day 28 (p less than 0.01). Positive trends were also recorded in the nine-hole peg test and in lower-limb measures including the 10-metre walk/run test.

Tolerability was clean: all adverse events were rated mild or moderate, with no serious adverse events and no discontinuations. The Aarhus-based company said the durable post-treatment effect points to a possible functional or structural recovery at the neuromuscular junction, rather than simple symptomatic relief during dosing.

Dr Herrmann said: "We are encouraged by the improvements in muscle strength and patient-reported outcomes, as well as the apparent persistence of benefits after treatment discontinuation, which may point to a meaningful effect on neuromuscular function in patients."

Disease and competitive context

CMT affects roughly one in 2,500 people worldwide, with an estimated 135,000 patients in the US alone. Despite being among the most prevalent rare neuromuscular conditions, it has no FDA-approved pharmacological treatments; care remains supportive, relying on physiotherapy and orthotics. That unmet need has attracted growing interest from the neuromuscular drug development community, though the space is far less crowded than comparable rare-disease areas such as spinal muscular atrophy or Duchenne muscular dystrophy, where multiple approved agents now compete.

Ignaseclant targets the skeletal muscle-specific chloride ion channel CIC-1, inhibiting it to enhance muscle excitability and responsiveness to weak neural signals. NMD Pharma positions this mechanism as first-in-class and distinct from gene-therapy or antisense approaches that target the underlying nerve pathology in CMT. Rather than correcting the genetic defect, ignaseclant aims to compensate downstream at the muscle itself, a strategy that could in principle apply across CMT subtypes regardless of genotype. The compound already holds FDA orphan drug designation for both CMT and generalised myasthenia gravis, the latter supported by earlier Phase 1b/2a data.

NMD Pharma has raised approximately $180 million from investors including Novo Holdings, Lundbeckfonden BioCapital, Roche Venture Fund, and Jeito Capital. The company said the SYNAPSE-CMT findings support advancement into larger and longer-term studies, though no Phase 3 timeline or partnership has been announced. Regulatory watch points include the design of a pivotal study that satisfies both FDA and EMA on endpoint selection in a disease with historically limited validated outcome measures.