Michael Panzara, MD, Chief Medical Officer at Neurvati Neurosciences and GRIN Therapeutics, discusses topline results of the Honeycomb trial for GRIN-related neurodevelopmental disorder with gain-of-function (GoF) variants.
GRIN-related neurodevelopmental disorders are a family of rare genetic conditions caused by pathogenic mutations in the GRIN gene. These disorders are characterized by childhood-onset epilepsy, developmental delay, movement disorders, and features of autism spectrum disorder. The symptoms a child experiences and the severity of the disorder can vary widely.
The Honeycomb trial is an ongoing global Phase 1b open-label trial evaluating the safety, tolerability, pharmacokinetics and efficacy of radiprodil in patients with GRIN-related neurodevelopmental disorder with GoF variants.
Radiprodil is an selective, potent negative allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor subtype 2B (NR2B or GluN2B). The investigational drug has been shown to modulate GluN2B-NMDA receptors and have an antiseizure effect.
Results from the trial illustrated radiprodil was generally well-tolerated. Common adverse events were associated with infections or underlying disease symptoms. Patients in the qualifying seizure cohort experienced a median reduction of 86% in countable motor seizures (CMS) frequency versus baseline. Additionally, 71% of patients had a greater than 50% reduction in CMS and six out of seven were seizure-free for 80% of days in the eight-week maintenance period. Favorable clinical outcomes were also observed on the Clinician and Caregiver Global Impressions of Change (CGI-C and CaGI-C) and the Aberrant Behavior Checklist – Community (ABC-C).
Next steps include a phase 3 randomized, double-blind, placebo-controlled, pivotal trial with two cohorts of patients with confirmed GoF mutations in the GRIN1, GRIN2A, GRIN2B, or GRIN2D genes. One cohort will enroll patients who have experienced qualifying CMS and a second cohort enrolling patients without qualifying CMS.
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To learn more about GRIN-related neurodevelopmental disorders and other rare neurological disorders, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/