Rapport Therapeutics says Phase 2a trial of RAP-219 met primary endpoint

Rapport Therapeutics (RAPP) announced that the Phase 2a clinical trial of RAP-219 in patients with drug-resistant focal onset seizures met its primary endpoint, demonstrating a statistically significant reduction in long episodes – an objective electrographic biomarker for clinical seizure reduction – compared with baseline over the 8-week treatment period. In the trial, RAP-219 also demonstrated a statistically significant and clinically meaningful reduction in clinical seizures compared with baseline. RAP-219 was generally well tolerated. The Company plans to advance RAP-219 into two Phase 3 pivotal trials in the third quarter of 2026. RAP-219 is a potential first-in-class, investigational TARPgamma8-specific AMPAR negative allosteric modulator. The Phase 2a clinical trial of RAP-219 is a proof-of-concept, multi-center, open-label study designed to evaluate the efficacy, safety, and tolerability of RAP-219 in adult patients with drug-resistant focal onset seizures. The trial enrolled 30 patients with focal onset seizures who had an implanted RNS System. Patients received 0.75 mg RAP-219 oral tablet daily for 5 days followed by 1.25 mg RAP-219 oral tablet daily for the remainder of the 8-week treatment period. The primary efficacy endpoint was the change in frequency of RNS-recorded long episodes in patients with focal onset seizures evaluated both as the proportion of responders achieving greater than or equal to30% reduction in LEs from baseline, which has been demonstrated to be associated with greater than or equal to50% reduction in clinical seizures, and median percent change from baseline in LE frequency. Secondary endpoints include clinical seizure frequency reductions, safety, and tolerability. Topline efficacy and tolerability data shared today are for the treatment period. The Phase 2a trial 8-week follow-up period is currently ongoing. Efficacy findings from the Phase 2a trial achieved statistically significant results for primary LE endpoints and key secondary endpoints of clinical seizures. In the 8-week treatment period, 85.2% of patients achieved greater than or equal to30% reduction in LEs from baseline, 72.0% achieved greater than or equal to50% reduction in clinical seizures from baseline, and 24% of patients achieved seizure freedom. RAP-219 was generally well-tolerated in the trial, with the majority of treatment-emergent adverse events being mild and a low discontinuation rate: No serious adverse events were reported during the treatment period All TEAEs reported were mild or moderate in severity 3 patients discontinued treatment due to TEAEs The most common TEAEs reported were dizziness, headache, fatigue, fall, nausea, and somnolence.