Radiprodil Gets Breakthrough Designation for Seizures Associated With Rare Gene Disorder

The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to radiprodil for the treatment of seizures associated with glutamate receptor inotropic N-methyl-D-aspartate-associated (GRIN)-related neurodevelopmental disorder with gain-of-function (GoF) mutations. 

GRIN-related neurodevelopmental disorder is a genetic disorder caused by mutations in GRIN genes which can occur as early as infancy. It is characterized by developmental delays, epilepsy, movement disorders, intellectual disabilities, and behavioral issues. Radiprodil, a negative allosteric N-methyl-D-aspartate receptor subtype 2B modulator, has demonstrated an antiseizure effect in preclinical seizure and epilepsy models. 

The designation was supported by data from the open-label phase 1b Honeycomb trial (NCT05818943), which evaluated the safety, tolerability, pharmacokinetics, and efficacy of radiprodil for the treatment of GRIN-related disorder in children aged 6 months to 12 years with a GoF genetic variant. The study included 1 cohort with treatment-resistant seizures with or without behavioral symptoms and 1 cohort with no qualifying seizures with behavioral symptoms. All study participants received oral radiprodil twice daily. 

Findings showed there was a median reduction of 86% in countable motor seizure (CMS) frequency compared with baseline in the seizure cohort. Notably, 71% of patients had a greater than 50% reduction in CMS and 6 out of 7 patients had no seizures during at least 80% of days during the 8 week maintenance period. There were also clinical improvements seen, regardless of seizure occurrence, in the Clinician and Caregiver Global Impressions of Change and the Aberrant Behavior Checklist – Community. 

As for safety, radiprodil was well-tolerated, with most commonly treatment-emergent adverse events being those associated with infections or underlying disease symptoms. 

“The FDA’s decision to designate radiprodil as a Breakthrough Therapy underscores its potential as a treatment option for patients who currently have no approved therapies,” said Bruce Leuchter, MD, President and Chief Executive Officer at Neurvati Neurosciences and GRIN Therapeutics. “Radiprodil’s mechanism, which targets the underlying disease biology, has demonstrated remarkable reductions in seizures in our Phase 1b open-label study and has the potential to meaningfully impact the non-seizure symptoms associated with this neurodevelopmental disorder.”

According to GRIN Therapeutics, a pivotal phase 3 trial for radiprodil in GRIN-related neurodevelopmental disorder is expected to begin in mid-2025.

This article originally appeared on MPR