GRIN Therapeutics, a leader in the development of therapies to treat serious neurodevelopmental disorders, today announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to radiprodil, the company’s investigational, potent negative allosteric modulator selectively targeting the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B), for the treatment of seizures associated with GRIN-related neurodevelopmental disorder with gain-of-function (GoF) mutations.
“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. Our team is executing with urgency to advance the Phase 3 study and bring this potential first-in-class treatment to patients as quickly as possible. We look forward to working closely with the FDA throughout this process to ensure a rigorous and efficient development path.”
Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). This designation grants radiprodil access to all the benefits of Fast Track designation, as well as intensive guidance by the FDA on an efficient drug development program and organizational commitment involving FDA senior managers.
“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 Professor Jacqueline A. French, MD, Professor in the Department of Neurology at NYU Grossman School of Medicine, Division Director of Epilepsy, 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.”
Breakthrough Therapy designation of radiprodil was supported by positive data from the Phase 1b Honeycomb study in pediatric patients with confirmed GoF mutations across GRIN genotypes. The data showed that treatment with radiprodil appeared to be generally well tolerated. Patients in the qualifying seizure cohort experienced a median reduction of 86% in countable motor seizure (CMS) frequency compared to baseline. During the trial period, 71% of patients had a greater than 50% reduction in CMS and six of seven were seizure-free during at least 80% of days in the eight-week maintenance period. Clinicians and caregivers generally assessed patients as improved clinically over the course of the study regardless of the occurrence of seizures as measured by Clinician and Caregiver Global Impressions of Change (CGI-C and CaGI-C) and the Aberrant Behavior Checklist – Community (ABC-C). Adverse events most commonly observed were those associated with infections or underlying disease symptoms. Three patients experienced an SAE associated with infection; all were assessed as unrelated to radiprodil.
The company remains on track to initiate a Phase 3 pivotal trial for radiprodil in GRIN-related neurodevelopmental disorder in mid-2025. The Phase 3 trial will aim to evaluate the impact of targeted treatment on core aspects of the disease, including seizures, behavioral abnormalities and functional outcomes. GRIN Therapeutics is backed by a $200M capital commitment from Blackstone Life Sciences.
