The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to Grin Therapeutics’ radiprodil for treating seizures associated with glutamate receptor, ionotropic, N-methyl D-aspartate (GRIN)-related neurodevelopmental disorder with gain-of-function (GoF) mutations.
The decision was based on the outcomes from the Phase Ib Honeycomb trial.
Honeycomb involved paediatric subjects with confirmed mutations of GoF across GRIN genotypes, demonstrating radiprodil's good tolerability.
Subjects experienced a median decrease of 86% in countable motor seizure (CMS) frequency in comparison with baseline.
71% of them saw a decrease in CMS by more than half, with six out of seven subjects seizure-free for at least 80% of the days during the maintenance period of eight weeks.
The trial also reported positive assessments from clinicians and caregivers, using measures such as the Clinician and Caregiver Global Impressions of Change and the Aberrant Behavior Checklist – Community.
Radiprodil is an investigational, potent negative allosteric modulator that targets the N-methyl-D-aspartate receptor subtype 2B. It now benefits from fast-track advantages and the agency’s intensive guidance on drug development programmes.
Mutations in GRIN genes lead to GRIN-related neurodevelopmental disorders. A Neurvati Neurosciences company, Grin Therapeutics is supported by a $200m capital commitment from private investment platform Blackstone Life Sciences and is preparing for a Phase III pivotal trial set to commence in mid-2025.
This trial will further evaluate radiprodil's impact on seizures, abnormalities in behaviour and functional outcomes in individuals with GRIN-related neurodevelopmental disorder.
Neurvati Neurosciences and Grin Therapeutics president and CEO Bruce Leuchter stated: "Radiprodil’s mechanism, which targets the underlying disease biology, has demonstrated remarkable reductions in seizures in our Phase Ib 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 III 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.”
