FDA Grants Orphan Drug Status to Radiprodil for GRIN-Related Neurodevelopmental Disorder

GRIN Therapeutics, a prominent name in the field of neurodevelopmental disorder treatments, has announced a significant milestone for its investigational drug, radiprodil. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation for radiprodil, aimed at treating GRIN-related neurodevelopmental disorder (NDD). This drug specifically targets the N-methyl-D-aspartate receptor subtype 2B (NR2B), functioning as a negative allosteric modulator.

The company is preparing to launch a pivotal Phase 3 clinical trial for radiprodil by mid-2025, focusing on patients with gain-of-function (GoF) mutations associated with GRIN-related NDD. Currently, an open-label global trial is underway, assessing radiprodil for conditions like tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II.

Michael A. Panzara, MD, MPH, Chief Medical Officer at Neurvati Neurosciences and GRIN Therapeutics, emphasized the progress being made towards offering the first treatment for GRIN-related NDD. He highlighted that the FDA's Orphan Drug designation is a vital step, supported by promising clinical data. The upcoming Phase 3 trial will evaluate radiprodil’s impact on seizures, behavioral issues, and overall functional outcomes in affected individuals. Panzara expressed gratitude to patients and families supporting this research.

The Orphan Drug designation is a strategic move to foster innovation and research into treatments for rare diseases affecting fewer than 200,000 people in the United States. This designation offers drug developers the potential for seven years of market exclusivity post-approval, during which the FDA generally refrains from approving similar drugs for the same conditions. In February 2025, radiprodil also received Breakthrough Therapy designation for treating seizures in GRIN-related NDD patients with GoF mutations.

Anne-Marie Li-Kwai-Cheung, Senior Vice President of Development, Regulatory, and Quality at Neurvati Neurosciences and GRIN Therapeutics, expressed enthusiasm for the continued engagement with the FDA. The Breakthrough Therapy designation is expected to aid in advancing the Phase 3 program, aiming to bring radiprodil to those in need. She acknowledged the urgent demand from clinicians and patients for effective treatments for GRIN-related disorders and reiterated the team’s dedication to fast-tracking the development and regulatory processes.

GRIN-related neurodevelopmental disorder, a rare pediatric condition caused by mutations in GRIN genes, presents a spectrum of symptoms including developmental delays, intellectual disabilities, epilepsy, and behavioral problems. Diagnosis often occurs around age two or later, as developmental milestones are missed. Currently, no approved therapies exist for this disorder.

Radiprodil stands out as a selective and potent modulator of the NR2B receptor, showing promise in preclinical studies for its antiseizure effects, particularly in models with enhanced GluN2B NMDA transmission. This is crucial in GRIN-related NDD with GoF mutations. Additionally, assays on brain tissues from TSC and FCD lesions indicate enhanced GluN2B NMDA expression, suggesting radiprodil's potential in managing seizures in these conditions.

GRIN Therapeutics remains committed to pioneering precision therapeutics for pediatric neurodevelopmental disorders, driven by the vision of offering hope to patients and their caregivers. The company's progress in clinical trials, including the promising outcomes from a Phase 1b/2a trial, underscores its dedication to advancing radiprodil through the necessary stages to potentially offer a groundbreaking treatment option for these challenging conditions.