Rapport Therapeutics: Positive Epilepsy Study Outcomes, Advancing to Phase 3 Trials in 2026

Rapport Therapeutics reported positive results from a Phase 2a trial of RAP-219 in drug-resistant focal onset seizures, meeting its primary endpoint and demonstrating a significant reduction in long episodes and clinical seizures compared to baseline. The company plans to advance RAP-219 into two Phase 3 pivotal trials in Q3 2026 and expects to present additional efficacy analyses in 2026.

Rapport Therapeutics, Inc. (Nasdaq: RAPP) has announced positive results from its Phase 2a clinical trial of RAP-219 in drug-resistant focal onset seizures. The trial, conducted in adult patients with focal onset seizures who had an implanted RNS® System, met its primary endpoint, demonstrating a statistically significant reduction in long episodes (LEs) and clinical seizures compared to baseline [2].

In the trial, RAP-219 achieved a 77.8% reduction in clinical seizures (p=0.01) and 24% of patients achieved seizure freedom over the 8-week treatment period (p0.0001). The drug was generally well tolerated, with no serious adverse events reported. These results support the advancement of RAP-219 into two Phase 3 pivotal trials, scheduled to begin in the third quarter of 2026 [2].

The primary efficacy endpoint was the change in frequency of RNS-recorded long episodes (LEs) in patients with focal onset seizures, evaluated as the proportion of responders achieving ≥30% reduction in LEs from baseline. Secondary endpoints included changes in clinical seizure frequency and safety metrics [2].

The trial design leveraged intracranial electroencephalography (iEEG) data from the RNS System to track LEs, offering a more granular and objective metric than traditional seizure counts. This approach allows for a clearer understanding of RAP-219’s mechanism of action, which involves modulating specific brain regions via receptor-associated proteins (RAPs) [1].

The positive trial results are a significant milestone for Rapport Therapeutics, which is focused on developing precision medicines for neurological and psychiatric disorders. The company plans to present additional efficacy analyses in 2026.

References:
[1] Rapport Therapeutics to Announce Topline Results for RAP-219 Phase 2a Trial in Focal Onset Seizures on Monday, September 8, 2025 [https://www.globenewswire.com/news-release/2025/09/05/3145488/0/en/Rapport-Therapeutics-to-Announce-Topline-Results-for-RAP-219-Phase-2a-Trial-in-Focal-Onset-Seizures-on-Monday-September-8-2025.html]
[2] Rapport Therapeutics Announces Positive Topline Results from Phase 2a Trial of RAP-219 in Drug-Resistant Focal Onset Seizures [https://finance.yahoo.com/news/rapport-announces-positive-topline-results-100000227.html]