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

The FDA has granted orphan drug designation (ODD) to radiprodil (GRIN Therapeutics) for the treatment of GRIN-related neurodevelopmental disorder (NDD). Designed as a negative allosteric modulator that selectively targets N-methyl-D-aspartate receptor subtype 2B, radiprodil is slated to be investigated in a pivotal phase 3 trial in 2025 for the treatment of GRIN-related NDD with gain-of-function (GoF) mutations.¹

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With ODD, radiprodil can benefit from tailored FDA support towards research and development that could eventually lead to full regulatory approval, which would provide a treatment for the thousands of patients that live with this rare disorder. In addition, radiprodil was granted breakthrough disease designation in February 2025 by the FDA for the treatment of seizures associated with GRIN-related NDD in patients with GoF mutations. The 2 designations are poised to propel raidprodil towards full FDA approval in the future.^1,2

At the American Epilepsy Society (AES) Annual Meeting in December 2024, GRIN Therapeutics presented data from the global, open-label, phase 1b Honeycomb trial that investigated the tolerability, safety, pharmacokinetics, and efficacy of radiprodil. In the trial, radiprodil was generally well-tolerated among patients, with the most common observed adverse events associated with underlying disease symptoms or infections. Among patients in the qualifying seizure cohort, there was a median reduction of 86% in countable motor seizures (CMS) frequency compared with baseline, a consistent observation observed across all GRIN genotypes.³

Furthermore, throughout the trial period, 71% of patients treated with radiprodil had a greater than 50% in CMS, while 6 of the 7 participants were seizure-free during at least 80% of days throughout the 8-week maintenance period. Importantly, the study investigators observed signs of a favorable effect on clinical outcomes regardless of the occurrence of seizures, as measured by 2 scores: Clinician and Caregiver Global Impressions of Change and the Aberrant Behavior Checklist—Community.³

The design of the phase 3 trial, a randomized, double-blind, placebo-controlled study, is set to include 2 cohorts of patients with confirmed GRIN mutations. These include GRIN1, GRIN2A, GRIN2B, and GRIN2D genes. The investigators intend to have a cohort of enrolled patients who have experienced qualifying CMS, and another cohort of patients without such seizures. Results from this pivotal trial will aid investigators in determining the next steps in radiprodil’s clinical development.³

“We are making rapid progress in our efforts to bring a first-ever treatment for GRIN-related neurodevelopmental disorder to patients,” Michael A Panzara, MD, MPH, chief medical officer at GRIN Therapeutics, said in a news release. “Supported by our promising clinical data, the FDA’s decision to grant orphan drug designation to radiprodil is the latest milestone in that effort.”¹

GRIN-related NDD comprises rare, genetically defined pediatric NDDs caused by mutations in GRIN genes. Diagnosis of such a disorder is typically not confirmed until a child is aged 2 years or later, when a child can be observed failing to reach developmental milestones. Signs of GRIN-related NDD include the potential of intellectual disabilities, developmental delay, epilepsy, muscular hypotonia, movement disorders, spasticity, and feeding and behavioral difficulties.³

Given the lack of approved therapies for GRIN-related NDD, radiprodil’s clinical development should be closely watched by treatment providers and patients alike.

REFERENCES

1. GRIN Therapeutics. GRIN Therapeutics receives FDA orphan drug designation for radiprodil for the treatment of GRIN-related neurodevelopmental disorder. News Release. Released March 17, 2025. Accessed March 18, 2025. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://neurvati.com/wp-content/uploads/Radiprodil-Orphan-Drug-Announcement-Release-FINAL.pdf

2. GRIN Therapeutics. GRIN Therapeutics receives FDA breakthrough therapy designation for radiprodil. News Release. Released February 25, 2025. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://neurvati.com/wp-content/uploads/Radiprodil-Breakthrough-Therapy-Designation-Final.pdf

3. GRIN Therapeutics. GRIN Therapeutics presents data from Honeycomb trial of radiprodil at the American Epilepsy Society Annual Meeting. News Release. Released December 9, 2024. Accessed March 18, 2025. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://neurvati.com/wp-content/uploads/AES-2024-Press-Release-Final-PDF.pdf