NMD Pharma is “accelerating development” of its lead rare disease candidate, ignaseclant, in Charcot-Marie-Tooth (CMT), despite the drug failing to meet its primary endpoint in a mid-stage trial.
During the 28-day, Phase IIa SYNAPSE-CMT study (NCT06482437), patients given the oral small molecule did not experience significant improvements in six-minute walk test (6MWT) scores at 21 days compared with placebo, missing the trial’s primary endpoint.
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However, ignaseclant did demonstrate benefits through key secondary endpoints. This includes improvements in validated CMT functional outcome measures (CMT-FOM) over placebo, which were observed across the 21-day treatment period and the 28-day follow-up. CMT-FOM measures a patient’s strength and function across multiple domains – including mobility, balance and strength in extremities.
Ignaseclant also bettered patient hand-based measures, with those receiving the skeletal muscle-specific chloride ion channel 1 (CIC1) inhibitor experiencing a clinically meaningful improvement in handgrip and fine hand function, which NMD says supports the drug’s functional benefit “beyond gross motor performance”. This effect was also maintained following treatment discontinuation, suggesting that ignaseclant’s impacts could extend past short-lived muscle activation.
CMT patients receiving ignaseclant also self-reported improvements in both physical function and disease impact through the CMT-Health Index (CMT-HI), which characterises overall disease burden across 18 key themes.
The drug was well tolerated in the study, with treatment-emergent adverse events (TEAEs) being mild-to-moderate in severity and resulting in no study discontinuations.
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By GlobalDataCMT is a progressive genetic disorder commonly characterised by peripheral nerve damage, which can cause muscle weakness, muscle wasting, fatigue and sensory loss in the limbs. There are currently no approved therapies for CMT.
As a result, despite the primary endpoint miss, Dr David Herrmann, MBBCh, Chief of the Neuromuscular Division in the Department of Neurology at the University of Rochester Medical Center and CMT-SYNAPSE study investigator, believes the improvements in secondary endpoints are notable for patients.
Herrmann said: “There are currently no approved therapies for people with CMT, and it is encouraging to see improvement trajectories across multiple measures of muscle strength and function in a short clinical study. The improvements observed in hand strength and dexterity are particularly relevant for patients, as these functions directly affect daily activities.”
Progress in drugging CMT thus far
NMD Pharma’s CEO, Thomas Holm Pedersen, added that he was “highly encouraged” by the continued functional improvements observed in the SYNAPSE-CMT study.
“The clarity and coherence of improvements across other objective and patient-reported measures align closely with our understanding of ignaseclant’s mechanism of action,” Pedersen said. “We believe these results strongly support continued development of ignaseclant as a potential therapy to deliver meaningful functional benefit for patients living with CMT and will be accelerating the clinical development in this indication.”
Now, the Danish biotech will bank on the trial outcomes as a signifier of ignaseclant’s efficacy in CMT, as the company looks to “accelerate” the drug’s clinical development within the rare disease.
NMD is not the first company to progress its drug on secondary endpoints in CMT. After the mixed results of its Phase II/III INSPIRE trial (NCT07191912), Applied Therapeutics vied to submit an approval application to the US Food and Drug Administration (FDA) for its sorbitol dehydrogenase (SORD)-correcting CMT hopeful, govorestat.
Following a Type C meeting with the agency, the company is now planning an additional Phase III trial, with the company set to discuss the design with the FDA.
Meanwhile, Novartis is looking to get two of its CMT candidates across the line, with the company’s small molecule HDAC6 inhibitor, CKD-510, and its gene therapy, EDK060, both currently in Phase I trials. Novartis acquired the global development and commercialisation rights to CKD-510 through Korean biotech Chong Kun Dang, while it gained access to EDK060 through its $1bn acquisition of DTx Pharma.
