A phase 2a trial of NMD Pharma’s rare disease prospect ignaseclant has missed its primary endpoint. But, with patients improving on multiple secondary endpoints, the biotech is accelerating development of the drug candidate.
The study randomized 81 adults with Charcot-Marie-Tooth disease (CMT) types 1 or 2 to take ignaseclant or placebo. Ignaseclant is a small-molecule inhibitor of the skeletal muscle-specific chloride ion channel 1, a mechanism NMD has identified as a way to restore muscle activation and function. People with CMT, a rare neuromuscular disease, have debilitating muscle weakness and declining motor control.
Participants received ignaseclant or placebo twice daily for 21 days. At the end of the treatment period, NMD saw no significant difference between six-minute walk test results in the two arms, missing the primary endpoint.
Yet NMD committed to accelerating ignaseclant’s clinical development in CMT after seeing the data. The decision reflects prespecified secondary endpoints that the biotech said showed consistent and clinically meaningful improvements in muscle strength, motor performance and patient-reported outcomes. NMD said benefits emerged early and persisted after treatment stopped.
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The trial linked ignaseclant to improvements on a composite scale assessing strength and function across multiple domains, with the benefits over placebo seen during the treatment window continuing through Day 28. According to the biotech, the maintenance of functional gains after treatment discontinuation suggests ignaseclant has effects that extend beyond short-acting pharmacologic muscle activation.
NMD reported improvements in handgrip strength and fine hand function, plus gains on patient-reported assessments of physical function and disease impact. The patient-reported outcomes aligned with the objective functional findings, according to NMD.
Ana de Vera, M.D., chief medical officer at NMD, said in a statement that improvements had yet to plateau when treatment ended, suggesting results could get better with longer-term treatment. The mix of secondary endpoint efficacy data, absence of serious adverse events or drug discontinuations and lack of existing CMT drugs is fueling plans for further development.
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Pharnext thought it had the data for a CMT type 1A approval in 2018, only for the FDA to ask it to run an additional trial. The second phase 3 study missed its primary endpoint in 2023. Applied Therapeutics began a phase 3 trial in CMT sorbitol dehydrogenase deficiency last year, while Novartis is assessing EDK060, an asset from its $500 million DTx Pharma buyout, in CMT type 1A in an early-phase trial.
CMT is one of three main indications pursued by NMD. The biotech expects to report phase 2 data on ignaseclant in spinal muscular atrophy and generalized myasthenia gravis (gMG) this year. NMD reported phase 1/2a data in gMG in 2022 and started a phase 2b trial in the indication in 2024.
