Rapport's RAP-219 long-term study feeds Phase 3 bet after 77.8% seizure cut
An open-label safety extension enrolling now will report preliminary data in H2 2026, testing durability of the seizure reduction that sent RAP-219 into two pivotal trials.
Executive Summary
- Rapport Therapeutics is enrolling patients who completed its Phase 2a trial into a long-term, open-label extension that will test whether RAP-219's seizure reduction and tolerability hold up with continued dosing.
- The extension carries no formal role in the regulatory pathway, but it will report data alongside the two Phase 3 pivotal trials the earlier result was strong enough to justify starting.
- The company's TARPγ8-specific AMPAR mechanism has no resolved precedent in focal epilepsy, so this readout functions as the first extended-exposure look at a therapeutic hypothesis with no established competitor to benchmark against.
- A 30-patient, single-arm, open-label design limits how much the H2 2026 update can settle on its own; the value is what it adds to the durability and safety record ahead of pivotal data.
What the trial tests
The study, registered as NCT07219407, enrolls patients who completed the parent Phase 2a trial (RAP-219-FOS-201) with acceptable tolerability. Its primary endpoint is the incidence of treatment-emergent adverse events, making this fundamentally a tolerability study rather than an efficacy trial. Secondary endpoints track long-episode and clinical-seizure-free intervals and responder proportions over extended dosing, carrying the durability question the parent trial's eight-week window could not answer. The trial is Recruiting, moving from Not yet recruiting as of January 23, 2026, with an anticipated enrollment of 30 patients and a primary completion date of February 3, 2028. NCT07219407A Long-term Study of the Safety and Effectiveness of RAP-219 in Adults With Focal Onset SeizuresNCT07219407
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the parent trial showed
In the Phase 2a trial, RAP-219 met its primary endpoint of reducing RNS-recorded long episodes, an objective electrographic biomarker for seizure activity, compared with baseline over an 8-week treatment period. Patients achieved a 77.8% reduction in clinical seizures (p=0.01), and 24% reached seizure freedom during that period (p<0.0001). Jacqueline French, the trial's principal investigator and a professor at NYU Langone Health's Comprehensive Epilepsy Center, said the trial "represents the first time a novel antiseizure medication was evaluated in focal seizure patients using the RNS system with an objective biomarker of seizure activity". Rapport called RAP-219 well tolerated in that trial and said the data support advancing it into two Phase 3 pivotal trials. RapportRapport Announces Positive Topline Results from Phase 2a Clinical Trial of RAP-219 in Patients ...Sep 8, 2025
Timing and stability
Rapport has guided H2 2026 for preliminary results from this extension trial across six separate disclosures dating back to September 2025, with the window holding at July 1 through December 31, 2026, each time. The trial's only registry changes since its October 2025 posting are the recruitment-status update and no amendments to enrollment, endpoints, or the primary completion date, a pattern the registry-churn proxy labels stable. The enrollment target has not moved from its original 30, a hold flagged as within the routine band by the operational model's enrollment-change threshold rather than a shortfall. Rapport+1Rapport Announces Positive Topline Results from Phase 2a Clinical Trial of RAP-219 in Patients ...Sep 8, 2025A Long-term Study of the Safety and Effectiveness of RAP-219 in Adults With Focal Onset SeizuresNCT07219407
The competitive frame
No competitor trial in the focal-epilepsy landscape shares RAP-219's TARPγ8-specific AMPAR mechanism; the nearest neighbors identified in the indication, including azetukalner, brivaracetam, and cenobamate-class agents in Phase 3 and Phase 4 programs, work through different mechanisms such as Kv7 or SV2A modulation. That leaves RAP-219 without a validated same-target precedent to benchmark durability or long-term tolerability against, and this extension becomes the first extended human dataset for the mechanism in this population.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.