Radiprodil Designated a Breakthrough Therapy for GRIN-Related Neurodevelopmental Disorder

Radiprodil (GRIN Therapeutics, New York, NY), a selective, potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype SB (NR2B or GluN2B), has been granted Breakthrough Therapy designation by the Food and Drug Administration (FDA) for the treatment of seizures associated with GRIN-related neurodevelopmental disorder with gain-of-function (GoF) mutations. The decision was based on data from the phase 1b Honeycomb clinical study (NCT05818943), which showed that radiprodil treatment was well tolerated and associated with significant reductions in seizure frequency for children with GRIN disorders.

Honeycomb was a multicenter, phase 1b study that enrolled 15 participants aged ≥6months to ≤12 years with gain-of-function (GoF) mutations across GRIN genotypes.

In terms of results:

• Treatment with radiprodil was associated with an 86% reduction from baseline in countable motor seizures (CMS).
• 71% of radiprodil-treated participants experienced a >50% reduction in CMS.
• 6 of 7 radiprodil-treated participants were seizure-free during ≥80% of the 8-week maintenance period.
• Radiprodil treatment was associated with improvements across clinician- and caregiver-reported outcomes.

"Over the course of my career, it has been extremely rewarding to both see and be part of the progress of innovation in the development of targeted therapies for the treatment of genetically defined epilepsies and neurodevelopmental disorders such as GRIN-related neurodevelopmental disorder," said Jacqueline A. French, MD, Professor at the NYU Grossman School of Medicine, Division Director of Epilepsy and Co-Director of Epilepsy Clinical Trials at NYU Langone Health, Director of the Epilepsy Study Consortium, and Member of GRIN Therapeutics' Clinical Advisory Committee. "The increased engagement with FDA that Breakthrough Therapy designation brings will ensure that the radiprodil program, developed in partnership with the academic and advocacy communities, has the best chance of success."

In 2025, GRIN Therapeutics plans to initiate a phase 3 clinical trial investigating the impact of targeted radiprodil treatment on seizure, behavioral, and functional outcomes of GRIN-related neurodevelopmental disorders.