Study of NMD670 for generalized myasthenia gravis gets FDA OK

Phase 2b clinical trial is set to launch soon in US, Europe

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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NMD Pharma has been cleared by the U.S. Food and Drug Administration (FDA) to start a Phase 2b clinical trial testing NMD670, an investigational CIC-1 inhibitor being developed for generalized myasthenia gravis (gMG).

Planned to launch in the coming months in the U.S. and Europe, the trial will enroll patients who test positive for antibodies against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK), the two most common types of antibodies causing the disease.

The study will test different doses of NMD670 against a placebo, both taken by mouth twice daily, to establish which dose works best and is least harmful to patients who have persistent or fluctuating symptoms of gMG despite receiving current standard of care.

“This is an important milestone for NMD Pharma, enabling us to progress our lead development candidate NMD670 into a Phase 2b trial,” Thomas Holm Pedersen, PhD, CEO of NMD Pharma, said in a company press release. “We are excited to bring forward a unique and validated muscle-targeted approach with promise to provide improvements in muscle function leading to clinically meaningful improvements in activities of daily living and quality of life.”

Myasthenia gravis (MG) occurs when self-reactive antibodies impair the communication between nerve and muscle cells, leading to muscle weakness and fatigue. In its generalized form, symptoms are widespread and aren’t restricted to any particular muscles, unlike other MG types.

“We hear from myasthenia gravis patients, patient organizations, and physician experts that a great number of myasthenia gravis patients continue to experience ongoing severe symptoms of muscle weakness and fatigue despite treatment,” Pedersen said.

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What does NMD670 do in gMG?

NMD670 is a small molecule designed to inhibit the ClC-1 ion channel, a protein that helps muscles relax and is found only in those that control voluntary movements. By inhibiting it, NMD670 should lead to gains in muscle strength and function.

In a study with a rat model of MG, single or multiple doses of NMD670 improved communication between nerve and muscle cells, restored muscle function, and improved the rats’ ability to move.

The study also reported on initial data from a small Phase 1/2a trial (CHDR1948) of NMD670, “which provided proof-of-mechanism and where clinically and statistically significant effects were seen in patients,” Pedersen said.

After completing the Phase 1 single ascending dose part in healthy volunteers, NMD670 was tested in 12 adults with mild gMG who were randomly assigned to either one of two NMD670 doses, or a placebo, in the Phase 2a part.

NMD670 was well tolerated by both healthy volunteers and patients, and led to clinically relevant improvements in the Quantitative Myasthenia Gravis (QMG) total score, a measure of disease severity, marking the first clinical evidence of its mechanism in action.

“These data provide important proof-of-mechanism as we progress our Phase 2 trial in spinal muscular atrophy and plan for the initiation of two other Phase 2 trials in AChR and MuSK antibody positive myasthenia gravis and Charcot-Marie-Tooth disease this year,” Pedersen said in another press release.

In late 2023, NMD Pharma secured €75 million (about $80 million) to complete the three Phase 2 trials of NMD670 in MG, along with spinal muscular atrophy and Charcot-Marie-Tooth disease, rare diseases also marked by muscle weakness.

NMD670 was granted orphan drug status in 2022 by the FDA to treat MG, a designation that qualifies drug makers for incentives to develop medications that might prevent, diagnose, or treat rare diseases.