RAP-219 · program

RAP-219 for Epilepsy

Phase 3RecruitingRapport Therapeutics, Inc. (RAPP)

Indications for RAP-219: Epilepsy · Phase 3 Bipolar disorder · Phase 2

RAP-219, a TARPγ8-selective AMPA receptor negative allosteric modulator, for focal onset seizures (and, later, primary generalized tonic-clonic seizures). The open-label Phase 2a trial RAP-219-FOS-201 (NCT06377930) in 30 adults with drug-resistant focal onset seizures and an implanted RNS System met its primary endpoint on RNS-recorded long episodes: 85.2% of patients had a ≥30% reduction (p<0.0001) and median long-episode frequency fell 71.0%; median clinical seizure frequency fell 77.8% (p=0.01), 72.0% had a ≥50% reduction and 24% were seizure-free over the 8-week treatment period (topline 2025-09-08).

Data current as of

Development timeline

Phase 3Jun 2026 – Jul 2029
  1. UpcomingClinicalTrials.gov estimated primary completion of Phase 3 FOCUS-1 (RAP-219 in focal seizures): July 2029.
  2. UpcomingInitial data from the open-label long-term safety trial of RAP-219 in focal onset seizures expected in Q4 2026.↗
  3. IND/CTA clearanceChina NMPA approves IND for RAP-219 Phase 3 trials in focal onset seizures↗
  4. Pivotal Phase 3 FOCUS-1 (NCT07563881) started (registry actual start date). Rapport reported on 2026-08-05 that the Phase 3 program began in Q2 2026 with FOCUS-1 and FOCUS-2 both enrolling.
  5. Trial startedPhase 3 FOCUS-1 of RAP-219 in focal onset seizures starts
Phase 2Oct 2024 – Apr 2026
  1. Conference presentationPhase 2a follow-up data for RAP-219 in focal onset seizures presented at AAN 2026↗
  2. Licensing dealRapport licenses Greater China rights to RAP-219 to Tenacia Biotechnology↗
  3. Phase 2a FOS-201 reached primary completion (registry actual date) after positive topline results for the 8-week treatment period were announced on 2025-09-08.
  4. metPositive Phase 2a topline in drug-resistant focal onset seizures: 85.2% achieved ≥30% long-episode reduction (p<0.0001); median clinical seizure reduction 77.8% (p=0.01); 24% seizure-free over 8 weeks.↗
  5. Open-label Phase 2a proof-of-concept trial RAP-219-FOS-201 (NCT06377930) started in adults with drug-resistant focal onset seizures with an implanted RNS System (30 enrolled).

Readouts

  • July 2029AnticipatedRegistry resultsNCT07563881

    ClinicalTrials.gov estimated primary completion of Phase 3 FOCUS-1 (RAP-219 in focal seizures): July 2029.

  • Q4 2026AnticipatedInterim analysisNCT07219407

    Initial data from the open-label long-term safety trial of RAP-219 in focal onset seizures expected in Q4 2026. ↗

  • 2025-09-08ReportedTopline datametNCT06377930

    Positive Phase 2a topline in drug-resistant focal onset seizures: 85.2% achieved ≥30% long-episode reduction (p<0.0001); median clinical seizure reduction 77.8% (p=0.01); 24% seizure-free over 8 weeks. ↗

Clinical trials in Epilepsy

NCT07594119RAP-219-FOS-302Phase 3Recruitingn=312

Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures

Started Sept 2026· Primary completion Jul 2029· 📍 2 sites across 1 country (United States)

NCT07563881RAP-219-FOS-301Phase 3Recruitingn=333

Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1

Started Jun 2026· Primary completion Jul 2029· 📍 3 sites across 1 country (United States)

NCT07219407RAP-219-FOS-901Phase 2Recruitingn=30

A Long-term Study of the Safety and Effectiveness of RAP-219 in Adults With Focal Onset Seizures

Started Dec 2025· Primary completion Feb 2028· 📍 7 sites across 1 country (United States)

NCT06377930RAP-219-FOS-201Phase 2Completedn=30

Study Evaluating the Safety and Efficacy of RAP-219 in Adult Participants With Refractory Focal Epilepsy

Started Oct 2024· Primary completion Sept 2025· 📍 12 sites across 1 country (United States)

metprimaryResponder proportion with ≥30% reduction in RNS-recorded long episodes (LEs) from baseline over the 8-week treatment period — 85.2% of patients (mITT N=27); median LE frequency reduction 71.0% (p=0.0001) (p<0.0001 (exact binomial vs 10% null))

Open-label, single-arm Phase 2a met its primary long-episode endpoints with high statistical significance; RAP-219 generally well tolerated.

metsecondaryClinical seizure frequency over the 8-week treatment period (median % change, ≥50% responders, seizure freedom) — Median clinical seizure reduction 77.8%; 72.0% with ≥50% reduction; 24.0% seizure-free (mITT-CS N=25) (77.8% median reduction p=0.01; responder and seizure-freedom p<0.0001)

Key secondary clinical seizure endpoints reached statistical significance versus prespecified null rates (no placebo arm).

Formulations

FormulationRouteRegimenPharmacokinetics
RAP-219 oral tablet (once daily)
Phase 2a focal onset seizures (RAP-219-FOS-201): 0.75 mg oral tablet daily for 5 days, then 1.25 mg daily for the rest of the 8-week treatment period. Phase 2 bipolar mania (RAP-219-BPM-201): 0.75 mg once daily after a 2- or 4-day titration, for 3 weeks inpatient. Phase 3 FOCUS-1/FOCUS-2: daily oral tablets at low/medium/high dose arms (dose levels not disclosed on the registry).
OralOnce dailyt½ 528 h

Mechanism of action (compound-wide)

Negative allosteric modulator of AMPA-type glutamate receptors that is selective for receptors complexed with the auxiliary subunit TARPγ8 (transmembrane AMPA receptor regulatory protein gamma-8, gene CACNG8). Because TARPγ8 is expressed mainly in forebrain regions such as hippocampus and neocortex and minimally in the hindbrain, the company's hypothesis is that region-selective dampening of AMPA signalling can suppress seizures (and mania) while avoiding the dose-limiting adverse effects of non-selective AMPA antagonists. A Phase 1 PET study with a companion radiotracer was run to confirm brain target occupancy and regional specificity.

TargetActionAffinity
TARPγ8primaryCACNG8NAM—ⓘ
AMPA receptorNAM—ⓘ

← Full RAP-219 compound page (identity, identifiers, all indications)

Sources

  1. Form 8-K Exhibit 99.1: Rapport Announces Positive Topline Results from Phase 2a Clinical Trial of RAP-219 in Patients with Focal Onset Seizures (2025-09-08) — Rapport Therapeutics, Inc. (SEC EDGAR)
  2. Form 8-K Exhibit 99.1: Rapport Therapeutics Reports Second Quarter 2026 Financials and Provides Business Update (2026-08-05) — Rapport Therapeutics, Inc. (SEC EDGAR)
  3. RAP-219-FOS-201: Study Evaluating the Safety and Efficacy of RAP-219 in Adult Participants With Refractory Focal Epilepsy — ClinicalTrials.gov
  4. RAP-219-FOS-301 (FOCUS-1): Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures — ClinicalTrials.gov
  5. RAP-219-FOS-302: Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures — ClinicalTrials.gov
  6. RAP-219-FOS-901: A Long-term Study of the Safety and Effectiveness of RAP-219 in Adults With Focal Onset Seizures — ClinicalTrials.gov
  7. Rapport Therapeutics Announces Positive Topline Results from its Phase 2 Trial of RAP-219 for the Treatment of Bipolar Mania (2026-10-20, wire copy) — Rapport Therapeutics, Inc. (via GlobeNewswire / BioSpace)
  8. Rapport Therapeutics Partners with Tenacia Biotechnology to Advance RAP-219 in Greater China (2026-03-10) — PharmaShots