Favorable Results for Radiprodil Tx for GRIN Disorders Leads to Launch of Study to Test Treatment in Those with Tuberous Sclerosis or Focal Cortical Dysplasia

Treatment with radiprodil (GRIN Therapeutics, New York, NY), a selective, potent negative allosteric modulator of the N-methyl-D-aspartate receptor subtype SB (NR2B or GluN2B), was well tolerated and associated with a significant reduction in seizure frequency in children with GRIN-related neurodevelopmental disorders. Following the reporting of findings from the phase 1b Honeycomb clinical study (NCT05818943), GRIN Therapeutics announced the initiation of the phase 1b/2b Astroscape clinical study (NCT06392009), which will investigate the safety and efficacy of radiprodil treatment for children with tuberous sclerosis (TSC) or focal cortical dysplasia (FCD) type II.

The multicenter phase 1b Honeycomb trial enrolled 15 patients aged ≥6 months to ≤12 years with gain-of-function (GoF) mutations in the GRIN1, GRIN2A, or GRIN1B genes. Participants were split into 2 cohorts, with Cohort 1 assessed for the frequency of countable motor seizures (CMS) within a 28-day screening period, and Cohort 2 assessed for baseline severity of nonseizure behavioral symptoms. The study included 2 periods, with participants who completed Part A being eligible for continued study treatment in Part B, consisting of an ongoing open-label extended treatment period.

• In Part A, participants treated with radiprodil showed an 86% reduction from baseline in seizure frequency.
• 71% of participants in Part A experienced a >50% reduction in CMS, 43% experienced a >90% reduction, and 1 participant was seizure free.
• Radiprodil appeared generally well tolerated throughout Part A and Part B of the study to date.
• Treatment emergent adverse events (TEAEs) included pyrexia, diarrhea, respiratory tract infection, abnormal behavior, agitation, cough, dystonia, fatigue, and gastroenteritis, which were associated with infections or underlying disease symptoms.

Astroscape is an open-label phase 1b/2b study that will evaluate radiprodil treatment at different doses for a targeted enrollment of 20 participants aged 6 months to 18 years with TSC or FCD type II with treatment-resistant seizures. Primary endpoints will include safety parameters, tolerability, and pharmacokinetic measures with key secondary endpoints assessing the effect of treatment on epileptic seizure frequency and severity and symptoms related to behavior, sleep, and quality of life. Participants who complete the treatment period may have the option to enroll in a long-term extension study.

"The initiation of treatment in the first patients enrolled in this landmark study is an important milestone for the TSC and FCD communities," said Dr. Manuel Toledo, MD, PhD, Head of the Epilepsy Unit at Vall d'Hebron University Hospital, Barcelona, Spain, who enrolled the first patient in the study. "We appreciate GRIN Therapeutics' commitment to making a positive difference for patients and families impacted by these serious conditions and we look forward to completing this clinical trial and reporting results as quickly as possible."