NMD Pharma’s oral drug ignaseclant improves muscle strength in CMT study
Company plans to discuss next steps with US, European regulators
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Ignaseclant, NMD Pharma’s experimental oral therapy, may help improve muscle strength and motor function in people with Charcot-Marie-Tooth disease (CMT) by making muscles respond better to weaker nerve signals.
That’s according to top-line data from the Phase 2a SYNAPSE-CMT trial (NCT06482437), which also showed consistency in benefits seen in clinical measures and patient-reported outcomes.
“We were encouraged that in this short-duration, exploratory study of ignaseclant, we saw consistent improvements from treatment across measures of muscle strength, motor function, and patient-reported outcomes,” said Thomas Holm Pedersen, PhD, CEO of NMD Pharma, in a written interview with Charcot-Marie-Tooth News. “Ignaseclant use thereby can help in performing everyday tasks with less effort, improving quality of life.”
Following an ongoing full analysis of the trial data, the company plans to present the results at a scientific meeting later this year. It will also discuss the next steps for ignaseclant with regulatory authorities in the U.S. and Europe, which should include the design of a pivotal trial intended to support approval of regulatory applications.
The company has already started producing the drug at a larger scale to support a longer clinical trial.
Ignaseclant targets key protein in muscle cells
Muscle weakness, fatigue, and limited mobility are common issues for people with CMT. Poor communication between nerves and muscles is part of the explanation for these symptoms.
Ignaseclant, previously known as NMD670, is intended to provide benefits by targeting the ClC-1 chloride channel, a protein found in muscle cells that normally “prevents unwanted muscle activation – like a natural brake on a car,” Pedersen said. “By inhibiting the ClC-1 chloride channel, ignaseclant makes muscle cells more responsive to the input from weaker nerve signals, and this helps with muscle activation and [helps] improve muscle strength and function,” he added.
Thomas Holm Pedersen, CEO of NMD Pharma. Courtesy of NMD Pharma.
According to Pedersen, the way in which igasenclant works makes it a treatment candidate for all CMT types, independent of specific disease-causing mutations.
The SYNAPSE-CMT trial evaluated the safety and efficacy of ignaseclant in 81 adults with CMT type 1 or type 2. The treatment candidate or a placebo was administered twice daily for 21 days, with a follow-up evaluation seven days later on day 28. Results showed that the treatment improved muscle strength and function, as assessed by the CMT Functional Outcome Measure.
This composite score, Pedersen said, includes several measures of mobility and muscle strength, assessed by clinicians and relevant to CMT. The benefits included marked improvements in handgrip strength and hand function that were sustained through day 28.
“Importantly, when patients stopped taking the study drug and returned one week later for final testing, those who had received ignaseclant largely maintained their improvements or continued to improve,“ Pedersen said. This suggests that effects extend “beyond transient and symptomatic recovery of muscle activation.”
“We did not observe a plateau at the end of the treatment window, suggesting the potential for further benefit with longer-duration therapy,” added Ana de Vera, MD, the company’s chief medical officer, in the press release. “We look forward to reviewing the full [data set] and engaging with CMT experts and regulatory authorities to define next steps.”
Trial participants reported improvements in physical function
Participants in the trial also reported improvements in physical function and disease impact, as assessed by the CMT Health Index. According to Pedersen, this suggests meaningful differences in how patients function on a daily basis.
“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,” said David Herrmann, MD, a CMT-SYNAPSE trial investigator at the University of Rochester Medical Center, in the press release.
However, the trial failed to meet its primary endpoint of demonstrating benefits over the placebo in the six-minute walk test, or the maximum distance a person can walk in six minutes on a flat surface. Pedersen emphasized that the six-minute walk test may not be the most sensitive measure to capture change in a short CMT study.
The results support further clinical testing of ignaseclant over longer treatment periods to better understand the durability and full potential of these improvements for people living with CMT.
The treatment was safe and well-tolerated, with no serious adverse events. No adverse event required stopping the treatment.
“The results support further clinical testing of ignaseclant over longer treatment periods to better understand the durability and full potential of these improvements for people living with CMT,” Pedersen said.
Pedersen further emphasized the role patients played in making the study possible. “We are grateful to the CMT patients who volunteered to enroll and those who participated in the trial,” he said, “and to the CMT community as a whole for their continued support as we endeavour to discover valuable new information and data on this rare disease.”
Last year, ignaseclant received orphan drug status from the U.S. Food and Drug Administration for the treatment of CMT. Besides CMT, ignaseclant is also being developed for generalized myasthenia gravis and spinal muscular atrophy.
