Rapport Therapeutics announced positive Phase IIa results for RAP-219, an experimental drug targeting drug-resistant focal onset seizures; mean reduction in seizures was approximately 78%, with 24% of participants seizure-free over two months31.
The Phase IIa trial used the RNS neurostimulation device to objectively measure seizure activity, making it the first trial to use this biomarker approach in this setting31.
Following these unprecedented results, RAP-219 will advance to two pivotal Phase III trials starting in Q3 2026; the company is also planning meetings with the FDA before trial initiation3159.
A leading epilepsy expert flagged a 'honeymoon effect,' cautioning that robust early responses seen in smaller mid-stage trials may not fully translate in larger, longer Phase III studies; objective biomarkers were cited as enhancing confidence but further validation is needed2.
Despite current treatments, around 40% of focal epilepsy patients continue to experience seizures, underlining persistent unmet need and the potential impact of new mechanisms like RAP-219's selective TARPĪ³8 targeting13.
Common side effects in the trial were mild to moderate (dizziness, headache, fatigue), and safety was generally favorable with few discontinuations3.
Market analysts and epilepsy specialists agree the magnitude of seizure reduction in the mid-stage trial far exceeds typical expectations for this patient group, but real-world effect sizes and population differences remain to be evaluated in Phase III123.
Sources:
1. https://www.biospace.com/drug-development/rapport-jumps-180-on-best-case-mid-stage-data-for-epilepsy-pill
2. https://firstwordpharma.com/story/6107680
3. https://newatlas.com/disease/epilepsy-drug-reduction-seizures/
5. https://www.statnews.com/2025/09/08/rapport-rap219-focal-seizures-epilepsy-trial-results/
9. https://www.biopharmadive.com/news/rapport-seizure-phase-2-study-results-stock-double/759486/