Rapport Announces Positive Topline Results from Phase 2a Clinical Trial of RAP-219 in Patients with Focal Onset Seizures
Rapport Therapeutics (NASDAQ: RAPP) announced positive topline results from its Phase 2a clinical trial of RAP-219 in patients with drug-resistant focal onset seizures. The trial met its primary endpoint with 85.2% of patients achieving 鈮�30% reduction in long episodes from baseline (p<0.0001). Notably, patients demonstrated a 77.8% median reduction in clinical seizure frequency (p=0.01), with 24% achieving complete seizure freedom during the 8-week treatment period.
The drug was generally well-tolerated, with mostly mild adverse events and no serious adverse events reported. Based on these promising results, Rapport plans to advance RAP-219 into two Phase 3 pivotal trials in Q3 2026, following an FDA end-of-Phase 2 meeting in Q4 2025. The company is also developing a long-acting injectable formulation to improve patient adherence.
Rapport Therapeutics (NASDAQ: RAPP) ha annunciato risultati topline positivi dal suo trial di Fase 2a su RAP-219 in pazienti con crisi focali resistenti ai farmaci. Lo studio ha raggiunto l'endpoint primario: il 85,2% dei pazienti ha ottenuto una riduzione 鈮�30% degli episodi prolungati rispetto al basale (p<0,0001). I pazienti hanno mostrato inoltre una riduzione mediana del 77,8% nella frequenza clinica delle crisi (p=0,01) e il 24% ha raggiunto completa libert脿 dalle crisi durante le 8 settimane di trattamento.
Il farmaco 猫 stato generalmente ben tollerato, con eventi avversi per lo pi霉 lievi e senza eventi avversi gravi riportati. Sulla base di questi dati incoraggianti, Rapport intende avviare due trial pivotali di Fase 3 nel terzo trimestre 2026, dopo un incontro con la FDA di fine Fase 2 previsto per il quarto trimestre 2025. L'azienda sta inoltre sviluppando una formulazione iniettabile a lunga durata per migliorare l'aderenza dei pazienti.
Rapport Therapeutics (NASDAQ: RAPP) anunci贸 resultados topline positivos de su ensayo de Fase 2a con RAP-219 en pacientes con crisis focales resistentes a f谩rmacos. El ensayo cumpli贸 el objetivo primario: el 85,2% de los pacientes logr贸 una reducci贸n 鈮�30% en episodios prolongados respecto al inicio (p<0,0001). Adem谩s, los pacientes presentaron una reducci贸n mediana del 77,8% en la frecuencia cl铆nica de crisis (p=0,01) y el 24% alcanz贸 libertad total de crisis durante las 8 semanas de tratamiento.
El f谩rmaco fue generalmente bien tolerado, con eventos adversos mayoritariamente leves y sin eventos adversos graves notificados. Con estos resultados prometedores, Rapport planea avanzar RAP-219 a dos ensayos pivotales de Fase 3 en el tercer trimestre de 2026, tras una reuni贸n de fin de Fase 2 con la FDA en el cuarto trimestre de 2025. La compa帽铆a tambi茅n desarrolla una formulaci贸n inyectable de larga duraci贸n para mejorar la adherencia del paciente.
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Rapport Therapeutics (NASDAQ: RAPP) a annonc茅 des r茅sultats topline positifs de son essai de phase 2a sur RAP-219 chez des patients pr茅sentant des crises focales r茅sistantes aux m茅dicaments. L'essai a atteint son crit猫re principal avec 85,2% des patients obtenant une r茅duction 鈮�30% des 茅pisodes prolong茅s par rapport au d茅part (p<0,0001). Les patients ont 茅galement montr茅 une r茅duction m茅diane de 77,8% de la fr茅quence clinique des crises (p=0,01), et 24% ont atteint une libert茅 compl猫te de crises durant les 8 semaines de traitement.
Le m茅dicament a 茅t茅 g茅n茅ralement bien tol茅r茅, avec principalement des effets ind茅sirables l茅gers et aucun effet ind茅sirable grave signal茅. Sur la base de ces r茅sultats prometteurs, Rapport pr茅voit d'engager RAP-219 dans deux essais pivots de phase 3 au T3 2026, apr猫s une r茅union de fin de phase 2 avec la FDA au T4 2025. La soci茅t茅 d茅veloppe 茅galement une formulation injectable 脿 action prolong茅e pour am茅liorer l'observance des patients.
Rapport Therapeutics (NASDAQ: RAPP) gab positive Topline-Ergebnisse seiner Phase-2a-Studie mit RAP-219 bei Patienten mit medikamentenresistenten fokalen Anf盲llen bekannt. Die Studie erreichte den prim盲ren Endpunkt: 85,2% der Patienten erzielten eine Reduktion 鈮�30% bei langen Episoden gegen眉ber dem Ausgangswert (p<0,0001). Zudem zeigten die Patienten eine mediane Reduktion der klinischen Anfallsh盲ufigkeit um 77,8% (p=0,01) und 24% erreichten w盲hrend der 8-w枚chigen Behandlungsperiode komplette Anfallsfreiheit.
Das Medikament wurde insgesamt gut vertragen, 眉berwiegend mit milden unerw眉nschten Ereignissen und ohne schwerwiegende Nebenwirkungen. Auf Basis dieser vielversprechenden Daten plant Rapport, RAP-219 im 3. Quartal 2026 in zwei Phase-3-Pivotalstudien zu bringen, nach einem End-of-Phase-2-Meeting mit der FDA im 4. Quartal 2025. Zudem arbeitet das Unternehmen an einer langwirksamen Injektionsformulierung zur Verbesserung der Patiententreue.
- Trial met primary endpoint with 85.2% of patients achieving 鈮�30% reduction in long episodes
- Significant 77.8% median reduction in clinical seizure frequency
- 24% of patients achieved complete seizure freedom
- 72% of patients achieved 鈮�50% reduction in clinical seizures
- No serious adverse events reported, with majority of side effects being mild
- Low discontinuation rate of only 10%
- Most common side effects included dizziness (26.7%), headache (16.7%), and fatigue (13.3%)
- Phase 3 trials won't begin until Q3 2026, indicating a lengthy development timeline
Insights
Rapport's RAP-219 shows impressive 77.8% seizure reduction in Phase 2a trial, with 24% of patients achieving complete seizure freedom.
The Phase 2a results for RAP-219 represent a significant breakthrough in the epilepsy treatment landscape. The trial demonstrated 85.2% of patients achieved 鈮�30% reduction in long episodes (p<0.0001) and 72% achieved 鈮�50% reduction in clinical seizures (p<0.0001). Most remarkably, 24% of patients achieved complete seizure freedom during the 8-week treatment period - an exceptionally rare outcome in drug-resistant epilepsy trials.
What makes these results particularly compelling is the dual validation approach: both the objective electrographic biomarker (long episodes recorded via RNS system) and the clinical seizure counts showed strong, concordant signals. This addresses a persistent challenge in epilepsy trials where patient-reported seizure counts can be unreliable.
The 77.8% median reduction in clinical seizure frequency (p=0.01) far exceeds typical responses seen with existing antiseizure medications, where 30-50% reductions are more common in treatment-resistant populations. The fact that these patients were already on a median of 3 other antiseizure medications, including newer agents like cenobamate, highlights the potential value of RAP-219's novel mechanism as a TARP纬8-specific AMPAR negative allosteric modulator.
The safety profile appears favorable, with no serious adverse events and only a 10% discontinuation rate. The side effect profile (dizziness, headache, fatigue) aligns with central nervous system agents but appears manageable based on the low discontinuation rate. This combination of efficacy and tolerability positions RAP-219 very favorably for Phase 3 trials and potential future adoption.
- Trial met primary long episode endpoints with high statistical significance, and RAP-219 was generally well tolerated
- Patients achieved
77.8% reduction in clinical seizures (p=0.01), with24% achieving seizure freedom for the 8-week treatment period (p<0.0001) - Data support advancement of RAP-219 into Phase 3 registrational trials
- Company to host a conference call today at 8:00 a.m. ET
BOSTON and SAN DIEGO, Sept. 08, 2025 (GLOBE NEWSWIRE) -- Rapport Therapeutics, Inc. (Nasdaq: RAPP) (鈥淩apport鈥� or the 鈥淐ompany鈥�), a clinical-stage biotechnology company dedicated to the discovery and development of small molecule precision medicines for patients with neurological or psychiatric disorders, today announced that the Phase 2a clinical trial of RAP-219 (RAP-219-FOS-201) in patients with drug-resistant focal onset seizures met its primary endpoint, demonstrating a statistically significant reduction in long episodes (LEs) 鈥� an objective electrographic biomarker for clinical seizure reduction 鈥� 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 TARP纬8-specific AMPAR negative allosteric modulator.
鈥淒espite the available therapies, up to
RAP-219 Phase 2a Focal Onset Seizures Trial Design
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庐 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 (LEs) in patients with focal onset seizures evaluated both as the proportion of responders achieving 鈮�
Topline Results
Topline efficacy and tolerability data shared today are for the treatment period (weeks 1-8). The Phase 2a trial 8-week follow-up period is currently ongoing.
Key Efficacy Results:
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,
| Outcome Measures for 8-Week Treatment Period | RAP-219 | |
| Long Episodes (LEs)鈥� primary efficacy endpoint mITT: N=27 | Patients with 鈮� | (p<0.0001) |
| Median reduction in LE frequency from baseline | (p=0.0001) | |
| Clinical Seizures (CS)鈥� key secondary endpoint mITT-CS: N=25 | Patients with 鈮� | (p<0.0001) |
| Patients who achieved seizure freedom | (p<0.0001) | |
| Median reduction in clinical seizure frequency from baseline | (p=0.01) | |
| mITT: patients with 鈮�3 weeks of treatment, 鈮� | ||
Key Safety and Tolerability Results:
RAP-219 was generally well-tolerated in the trial, with the majority of treatment-emergent adverse events (TEAEs) being mild and a low discontinuation rate:
- No serious adverse events (SAEs) were reported during the treatment period
- All TEAEs reported were mild (
78.5% ) or moderate (21.5% ) in severity (Grades 1 or 2) - 3 (
10% ) patients discontinued treatment due to TEAEs - The most common TEAEs reported (鈮�
10% incidence) were dizziness (n= 8,26.7% ), headache (n = 5,16.7% ), fatigue (n = 4,13.3% ), fall (n = 3,10.0% ), nausea (n = 3,10.0% ), and somnolence (n = 3,10.0% ).
鈥淭he efficacy data and tolerability profile seen in the Phase 2a trial demonstrate RAP-219鈥檚 potential to be an important treatment for patients with drug-resistant focal onset seizures. What鈥檚 particularly encouraging is the consistency of the significant improvements seen in the long episode biomarker responses and the clinical seizure reductions,鈥� said Abe Ceesay, chief executive officer of Rapport. 鈥淲ith these data and RAP-219鈥檚 emerging best-in-class profile, if approved, we believe RAP-219 could address a significant unmet need among patients, with the potential to support broad adoption among epileptologists and neurologists treating patients living with drug-resistant focal seizures.鈥�
Trial Patient Demographics and Baseline Characteristics
The demographics and baseline characteristics of patients enrolled in the Phase 2a study are consistent with that of patients expected in future registrational trials. The trial enrolled 12 women and 18 men, and the mean age of patients enrolled was 40.1 years. The mean age of enrolled patients at the time of their first seizure was 16.6 years. Patients were taking a median of 3 concomitant antiseizure medications, with the highest proportion of patients taking lamotrigine (
鈥淲e are excited by the strength of these data in both the electrographic biomarker and clinical seizure reductions. These results give us the confidence to progress RAP-219 into its next stage of clinical development,鈥� said Dr. Jeffrey Sevigny, M.D., chief medical officer of Rapport. 鈥淚mportantly, the baseline characteristics of patients enrolled, together with the broad cortical expression of TARP纬8 and the robust results in the trial, give us confidence in the translatability of the data into the Phase 3 drug-resistant focal onset seizure patient population. Given the persistent unmet need in focal epilepsy, we plan to move into two Phase 3 trials using traditional clinical seizure endpoints, with initiation expected in the third quarter of 2026.鈥�
Rapport plans to hold an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2025 and plans to initiate pivotal trials in the third quarter of 2026. The Company also expects to present additional efficacy analyses and 8-week follow-up results in 2026.
Additional RAP-219 Development Plans
By the end of 2025, Rapport plans to initiate an open-label long term safety trial to allow patients enrolled in the RAP-219-FOS-201 trial to continue on RAP-219. Preliminary results of the trial are expected in the second half of 2026.
Additionally, Rapport continues development of a long-acting injectable (LAI) formulation of RAP-219. Up to half of patients are nonadherent to prescribed ASMs, which can present a significant issue in optimizing treatment benefit and lead to potential breakthrough seizures. The Company believes a LAI formulation has the potential to improve patient adherence and expand the potential clinical utility across all of RAP-219鈥檚 indications.
Outside of epilepsy, Rapport is evaluating RAP-219 in a Phase 2 trial in bipolar mania. The trial is currently enrolling patients and is on track, with topline results expected in the first half of 2027. An update on the plan and timeline for initiation of a Phase 2 trial in diabetic peripheral neuropathic pain is expected later in 2025.
Conference Call Information
Rapport Therapeutics will host a conference call and live webcast at 8:00 a.m. ET / 5:00 a.m. PT on September 8, 2025, to discuss the data and provide a business update. Individuals interested in listening to the live conference call may do so by dialing (800) 715-9871 for U.S callers and (646) 307-1963 for other locations and reference conference ID 4762775, or from the webcast link in the 鈥淚nvestors鈥� section of the Company's website at聽. A webcast replay will be available in the investor relations section on the Company鈥檚 website for 90 days following the completion of the call.
About RAP-219
RAP-219 is a potential first-in-class, clinical-stage TARP纬8-specific AMPA receptor (AMPAR) negative allosteric modulator (NAM). Whereas AMPARs are distributed widely in the central nervous system, the receptor associated protein (RAP) TARP纬8 is expressed only in discrete brain regions, including the hippocampus and neocortex, where focal seizures often originate. By contrast, TARP纬8 has minimal expression in the hindbrain, where drug effects are often associated with intolerable adverse events. With this precision approach, the Company believes RAP-219 has the potential to provide a differentiated profile as compared to traditional neuroscience medications. Due to the role of AMPA biology in various neurological disorders and the selective targeting of TARP纬8, the Company believes RAP-219 has pipeline-in-a-product potential and is evaluating the compound as a transformational treatment for patients with focal onset seizures, bipolar disorder, and peripheral neuropathic pain.
About Rapport Therapeutics
Rapport Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing small molecule precision medicines for patients with neurological or psychiatric disorders. The Company鈥檚 founders have made pioneering discoveries related to the function of receptor associated proteins (RAPs) in the brain. Their findings form the basis of Rapport鈥檚 RAP technology platform, which enables a differentiated approach to generate precision small molecule product candidates with the potential to overcome many limitations of conventional neurology drug discovery. Rapport鈥檚 precision neuroscience pipeline includes the Company鈥檚 lead investigational drug, RAP-219, designed to achieve neuroanatomical specificity through its selective targeting of a RAP expressed in only discrete regions of the brain. The Company is currently pursuing RAP-219 as a potential treatment for drug-resistant focal onset seizures, bipolar mania and diabetic peripheral neuropathic pain. Additional preclinical and late-stage discovery stage programs are also underway, including targeting chronic pain and hearing disorders.
Availability of Other Information About Rapport Therapeutics
Rapport Therapeutics uses and intends to continue to use its Investor Relations website and LinkedIn (Rapport Therapeutics) as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company鈥檚 Investor Relations website and LinkedIn, in addition to following the Company鈥檚 press releases, SEC filings, public conference calls, presentations, and webcasts. The contents of the Company鈥檚 website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.
Forward-Looking Statements
Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words 鈥渁nticipate,鈥� 鈥渂elieve,鈥� 鈥渃ontinue,鈥� 鈥渃ould,鈥� 鈥渆stimate,鈥� 鈥渆xpect,鈥� 鈥渋ntend,鈥� 鈥渕ay,鈥� 鈥減lan,鈥� 鈥減otential,鈥� 鈥減redict,鈥� 鈥減roject,鈥� 鈥渟hould,鈥� 鈥渢arget,鈥� 鈥渨ill,鈥� 鈥渨ould鈥� and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding: the clinical development of RAP-219 for the treatment of focal onset seizures, bipolar mania, and diabetic peripheral neuropathic pain, including the initiation, timing, progress and results of the Company鈥檚 Phase 3 clinical trials in focal onset seizures, and a Phase 2 clinical trial of RAP-219 in bipolar mania, as well as other planned clinical trials; expectations for the activity, tolerability, and commercial potential of RAP-219; the future release of data from the ongoing 8-week follow-up period of the Phase 2a trial for RAP-219; expectations for a LAI formulation of RAP-219 and the potential of a LAI to improve patient adherence; the Company鈥檚 expectations for upcoming regulatory interactions; the potential of Rapport鈥檚 RAP technology platform; and expectations for Rapport鈥檚 uses of capital, expenses and financial results.
Forward looking statements are based on management鈥檚 current expectations and are subject to risks and uncertainties that could negatively affect Rapport鈥檚 business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company鈥檚 research and development activities; Rapport鈥檚 ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to preclinical and clinical development activities; the Company鈥檚 dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Rapport鈥檚 ability to attract, integrate and retain key personnel; risks related to the Company鈥檚 financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Rapport鈥檚 intellectual property protections; and risks related to the competitive landscape for Rapport鈥檚 product candidates; as well as other risks described in鈥� 鈥淩isk Factors,鈥� in the Company鈥檚 Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Rapport鈥檚 subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Rapport鈥檚 views only as of today and should not be relied upon as representing its views as of any subsequent date. Rapport expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.
Contact
Julie DiCarlo
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Rapport Therapeutics
FAQ
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