GRIN Therapeutics Reports Positive Honeycomb Trial Results for Radiprodil in GRIN Neurodevelopmental Disorder

GRIN Therapeutics, Inc., a prominent entity in the realm of neurodevelopmental disorder therapies, has reported promising results from their two-part global Phase 1b trial for radiprodil. This investigational drug, a selective and potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B), is being tested for its efficacy in treating GRIN-related neurodevelopmental disorder. The results were shared at the International League Against Epilepsy (ILAE) 15th European Epilepsy Conference in Rome, Italy.

Prof. Renzo Guerrini, MD, FRCP, FAES, and Director of the Neuroscience and Human Genetics Department at the Children's Hospital A. Meyer IRCCS, University of Florence, Italy, expressed optimism about the trial outcomes. He highlighted the potential of radiprodil to significantly reduce seizures and improve behavior in children with gain-of-function mutations who do not respond to current treatments. He noted that these encouraging results warrant continued research and development into the next phase.

The Honeycomb study involved 15 pediatric patients with confirmed gain-of-function mutations in the GRIN1, GRIN2A, or GRIN2B genes. The primary objectives were to assess the safety and pharmacokinetics of radiprodil, while secondary objectives focused on its efficacy in reducing seizures and improving behavioral symptoms. Patients were divided into two cohorts: one based on the frequency of countable motor seizures (CMS) during a 28-day screening period, and the other based on the baseline severity of non-seizure behavioral symptoms.

After initial screening and observation, patients began with a starting dose of 0.05 mg/kg of radiprodil, which was adjusted based on tolerability and pharmacokinetics. The dose was maintained through an eight-week period. Part B of the study, an open-label extended treatment period, continues for patients who completed Part A and are eligible for ongoing treatment.

As of the July 15 data cut, 15 patients were analyzed. The demographic and disease characteristics at baseline were representative of the targeted GRIN population and balanced between the seizure and non-seizure behavior cohorts. Cohort 1 exhibited high seizure activity at baseline, with a mean of 37.0 and a median of 25.5 CMS per patient. Cohort 2 had no CMS at baseline.

Radiprodil was generally well tolerated in both parts of the study. The most common treatment-emergent adverse events (TEAEs) included infections and symptoms related to underlying diseases like pyrexia, diarrhea, respiratory tract infections, abnormal behavior, agitation, cough, dystonia, fatigue, and gastroenteritis. No deaths occurred, and while three patients experienced serious adverse events (obstructive bronchitis, viral pneumonia, or adenovirus infection), none were linked to radiprodil, nor did they meet criteria to halt the study.

During Part A, patients treated with radiprodil experienced a median reduction of 86% in seizure frequency from baseline. Furthermore, 71% of patients saw a reduction in CMS of more than 50%, with 43% seeing a reduction of over 90%, and one patient becoming seizure-free. Both clinicians and caregivers reported general clinical improvements in patients throughout the study.

Bruce Leuchter, MD, President and CEO of Neurvati Neurosciences and GRIN Therapeutics, underscored the significance of these findings. He emphasized the need to swiftly move radiprodil into Phase 3 development, given its potential to address the unmet needs of patients with GRIN-related neurodevelopmental disorder. He also highlighted the considerable progress achieved since the company's inception three years ago, supported by Blackstone Life Sciences.

Radiprodil’s promising outcomes in this study provide a strong foundation for future research and potential regulatory discussions aimed at advancing the drug to a Phase 3 pivotal trial. GRIN Therapeutics, with substantial backing from Blackstone Life Sciences, continues its mission to develop precision therapeutics for pediatric neurodevelopmental disorders, offering hope to affected patients and their families.