Praxis announces accelerated development path for relutrigine in SCN2A and SCN8A DEE patients following positive FDA feedback
Praxis (NASDAQ: PRAX) said it reached alignment with the FDA after a Type B meeting and written advice on the protocol and SAP for relutrigine in SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs). The FDA agreed Praxis’ planned interim analysis of the EMBOLD cohort 2 study, scheduled for Q4 2025, may serve as the basis for an NDA submission in early 2026 if positive. The interim will use ~70% of 16-week study patients and is controlled at a 4% alpha; a negative interim would preserve a final analysis at 1% alpha (n≈80). Prior EMBOLD cohort 1 results showed an ANCOVA p-value of 0.0354 for seizure reduction versus placebo. Praxis also opened enrollment in the registrational EMERALD trial in Q3 2025, with completion expected in H2 2026.
Praxis (NASDAQ: PRAX) ha detto di aver raggiunto l'allineamento con la FDA dopo un incontro di tipo B e consigli scritti sul protocollo e sul SAP per la relutrigine nelle SCN2A e SCN8A encefalopatie epilettiche evolutive (DEEs). La FDA ha concordato che l'analisi intermedia pianificata dalla coorte EMBOLD 2 dello studio, prevista per Q4 2025, potrebbe servire come base per una presentazione NDA all'inizio del 2026 se i risultati siano positivi. L'interim utilizzerà circa il 70% dei pazienti dello studio di 16 settimane ed è controllato a un alpha 4%; un interim negativo preserverebbe una analisi finale a alpha 1% (n≈80). I precedenti risultati della EMBOLD coorte 1 hanno mostrato una p-valore ANCOVA di 0,0354 per la riduzione delle convulsioni rispetto al placebo. Praxis ha aperto anche l'iscrizione al trial registrazionale EMERALD nel Q3 2025, con completamento previsto nella seconda metà del 2026.
Praxis (NASDAQ: PRAX) dijo haber alcanzado alineamiento con la FDA tras una reunión de tipo B y asesoría por escrito sobre el protocolo y el SAP para la relutrigina en las ENEs DEE SCN2A y SCN8A (encefalopatías epilépticas developmental y evolutivas). La FDA estuvo de acuerdo en que el análisis interino planificado de la cohorte EMBOLD 2 del estudio, programado para el Q4 2025, podría servir como base para una presentación de NDA a principios de 2026 si es positivo. El interin o utilizará aproximadamente el 70% de los pacientes del estudio de 16 semanas y está controlado a un alpha del 4%; un interino negativo conservaría un análisis final a alpha 1% (n≈80). Resultados previos de la cohorte EMBOLD 1 mostraron un valor-p ANCOVA de 0.0354 para la reducción de convulsiones frente al placebo. Praxis también abrió la inscripción en el ensayo EMERALD, registracional, en Q3 2025, con finalización prevista para la parte alta de 2026.
Praxis (NASDAQ: PRAX)는 SCN2A 및 SCN8A 발달성 및 뇌전증 DEE에서 프로토콜 및 SAP에 대한 서면 자문과 함께 Type B 미팅 후 FDA와의 합의를 달성했다고 말했다. FDA는 EMBOLD 코호트 2의 연구 중간 분석이 2025년 4분기에 예정되어 있으며 양성일 경우 2026년 초 NDA 제출의 근거가 될 수 있다고 동의했다. 중간 분석은 16주 연구의 약 70%의 환자를 사용할 것이고 알파 4%로 제어된다; 중간 결과가 음수일 경우 최종 분석은 알파 1% (n≈80)로 보존된다. EMBOLD 코호트 1의 이전 결과는 대조군 대비 발작 감소에 대한 ANCOVA p값이 0.0354로 나타났다. Praxis는 또한 2025년 3분기에 등록 임상 EMERALD 시험의 등록을 개시했으며 2026년 하반기에 완료될 것으로 예상된다.
Praxis (NASDAQ: PRAX) a déclaré être parvenue à un alignement avec la FDA après une réunion de type B et des conseils écrits sur le protocole et le SAP pour la relutrigine dans les ENCEFALOPATHIES Épileptiques développementales SCN2A et SCN8A (DEEs). La FDA a accepté que l’analyse intermédiaire prévue de la cohorte EMBOLD 2 de l’étude, prévue pour Q4 2025, puisse servir de base à une soumission NDA au début de 2026 si les résultats sont positifs. L’intermédiaire utilisera environ 70% des patients de l’étude de 16 semaines et est contrôlé à un alpha de 4% ; un intermédiaire négatif préserverait une analyse finale à un alpha de 1% (n≈80). Les résultats antérieurs de la cohorte EMBOLD 1 ont montré une valeur-p ANCOVA de 0,0354 pour la réduction des crises par rapport au placebo. Praxis a également ouvert l’inscription à l’essai EMERALD, registrable, au Q3 2025, avec une complétion attendue au S2 2026.
Praxis (NASDQ: PRAX) gab bekannt, dass sie nach einem Type-B-Gespräch und schriftlicher Beratung zum Protokoll und SAP für Relutrigin bei SCN2A- und SCN8A-entwicklungsbedingten epileptischen Enzephalopathien (DEEs) eine Abstimmung mit der FDA erreicht haben. Die FDA stimmte zu, dass die geplante Zwischenanalyse der EMBOLD-Kohorte 2 der Studie, vorgesehen für Q4 2025, als Grundlage für eine NDA-Einreichung Anfang 2026 dienen könnte, sofern positiv. Die Zwischenanalyse wird ca. 70% der Patienten der 16-Wochen-Studie verwenden und ist bei einem Alpha von 4% kontrolliert; eine negative Zwischenanalyse würde eine abschließende Analyse bei Alpha 1% (n≈80) bewahren. Frühere EMBOLD-Kohorten-1-Ergebnisse zeigten einen ANCOVA-p-Wert von 0,0354 für die Reduktion von Anfällen gegenüber Placebo. Praxis eröffnete außerdem die Einschreibung in die registratorische EMERALD-Studie im Q3 2025, mit voraussichtlicher Fertigstellung in der 2. Hälfte 2026.
Praxis (بورصة ناسداك: PRAX) قالت إنها توصلت إلى تنسيق مع هيئة الغذاء والدواء الأمريكية FDA بعد اجتماع من النوع B ونصائح مكتوبة حول البروتوكول وخطة التحليل الإحصائي SAP لـ relutrigine في الحالات التطورية والصرعية الدماغية لمرض SCN2A وSCN8A (DEEs). وافقت FDA على أن التحليل المؤقت المخطط لدراسة EMBOLD Cohort 2، المقرر في الربع الرابع 2025، قد يكون أساساً لتقديم NDA في أوائل 2026 إذا كان إيجابياً. سيستخدم التحليل المؤقت نحو 70% من مرضى الدراسة التي تبلغ مدتها 16 أسبوعاً ويُدار عند ألفا 4%. إذا كان التحليل المؤقت سلبياً، فسيبقى التحليل النهائي عند ألفا 1% (ن≈80). أظهرت نتائج EMBOLD Cohort 1 السابقة قيمة-p من ANCOVA قدرها 0.0354 لإخماد النوبات مقارنة بالدواء الوهمي. كما فتحت Praxis باب التسجيل في تجربة EMERALD التنظيمية في الربع الثالث 2025، مع إكمال متوقع في النصف الثاني من 2026.
- FDA agreed interim analysis could support an NDA in early 2026
- Interim analysis planned for Q4 2025 using ~70% of 16-week patients
- EMBOLD cohort 1 showed seizure reduction vs placebo with ANCOVA p=0.0354
- Interim must be positive to enable NDA timing; a negative interim delays submission
- Final analysis requires n≈80 and stricter 1% alpha if interim not positive
- Target patient population is ultra-rare (~5,000 US patients), limiting market size
Insights
FDA alignment and a planned Q4 2025 interim could enable an NDA submission in early 2026 if results are positive.
Praxis reached documented alignment with the FDA after a Type B meeting and written advice, including agreement that an interim analysis of the ongoing EMBOLD cohort 2 could form the basis of an NDA submission. The interim is planned for
The principal dependency is the binary outcome of the interim analysis: only a positive interim would trigger the described accelerated NDA path to early
Comprehensive meeting with FDA conducted in Q3 in conjunction with Breakthrough Therapy Designation
Key aspects of a potential NDA application discussed and aligned with the Agency
Praxis plans to perform an interim analysis of the EMBOLD cohort 2 pivotal trial in Q4 2025, which if positive should serve as the basis of an NDA in early 2026
BOSTON, Nov. 04, 2025 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today announced that, following a comprehensive Type B meeting and recent meeting minutes and written advice on the protocol and SAP, it has reached alignment with the FDA on several aspects of the relutrigine program in SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs), including the use of the ongoing EMBOLD study to serve as the basis of substantial evidence of effectiveness for the NDA submission. The FDA agreed that Praxis’ proposed interim analysis, if positive, may serve as the basis of the NDA submission in early 2026. The interim analysis is planned to be conducted in the fourth quarter of 2025.
“We are appreciative of the recent collaborative discussion with the FDA about opportunities to bring relutrigine to SCN2A and 8A patients sooner, which came as a result of our breakthrough therapy designation (BTD),” commented Steven Petrou, chief scientific officer. “We reached alignment on key elements of the NDA with FDA, and upon a successful result from the upcoming interim analysis, we would quickly submit the NDA for relutrigine. This could be our second NDA under review, pending acceptance of the ulixacaltamide NDA.”
SCN2A- and SCN8A-DEEs are ultra-rare, life-threatening pediatric epilepsies characterized by early-onset, pharmacoresistant seizures, rapid neurodevelopmental decline, and high premature mortality. There are no FDA approved therapies. Off-label polytherapy with ASMs remains the only therapeutic option but is largely ineffective, carries substantial toxicity risks, and imposes a significant burden for the approximately 5,000 patients living with the condition in the US.
In the current cohort of the EMBOLD study, patients were randomized (1:1) to receive relutrigine QD for 16 weeks, or relutrigine QD for 12 weeks and matching placebo QD for 4 weeks, administered orally or via gastrostomy/jejunostomy tube (G/J-tube). The primary endpoint is the change in monthly (28-day) seizure frequency. The primary endpoint will be analyzed using an ANCOVA on log-transformed data. The ANCOVA model will include fixed effect for treatment group (relutrigine and placebo).
The interim analysis will be based off approximately
In the first cohort of EMBOLD, shared in September 2024, the results using the agreed upon endpoint and analysis methods with the FDA are summarized below:
| Placebo (n = 7) | PRAX-562 (relutrigine) (n = 15) | |
| Log-transformed change from baseline in seizure frequency during double-blind period, LSmean (SE) | -0.102 (0.223) | -0.688 (0.207) |
| Log Difference in LSMean (SE)) | -0.585 (0.259) | |
| ANCOVA p-value | 0.0354 |
Relutrigine is also being investigated in patients across all DEEs in the EMERALD trial. EMERALD is a registrational, 16-week, placebo-controlled study evaluating seizure reduction in patients diagnosed with developmental epilepsies evaluating relutrigine. Enrollment for the EMERALD study began in the third quarter of 2025 and is expected to be complete in the second half of 2026, receiving strong interest in the geographies where it is planned. Assuming successful conclusion of the EMBOLD study and subsequent NDA approval, if positive, the EMERALD study would serve as the basis for an sNDA by 2027.
About Relutrigine (PRAX-562)
Relutrigine is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathies (DEEs) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in severe DEEs. Relutrigine’s mechanism of precision sodium channel (NaV) modulation is consistent with superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of relutrigine have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. Relutrigine has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel modulation. Data from cohort 1 of the Phase 2 EMBOLD study demonstrated a well-tolerated, robust, short- and long-term improvement in motor seizures in a heavily pre-treated population, alongside maintained seizure freedom in some patients with SCN2A- and SCN8A-DEE. Relutrigine has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation from the FDA for the treatment of SCN2A-DEE, SCN8A-DEE and Dravet syndrome; as well as Breakthrough Therapy Designation (BTD), and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. To learn more about the EMERALD and EMBOLD studies, please visit ResilienceStudies.com.
About Praxis
Praxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across epilepsy and movement disorders, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, LinkedIn and Twitter/X.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Praxis’ future expectations, plans and prospects, including, without limitation, statements regarding the anticipated timing of our clinical trials, the development of our product candidates and the anticipated timing of regulatory submissions and interactions, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “endeavor,” “estimate,” “expect,” “anticipate,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995.
The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical trials; the expected timing of clinical trials, data readouts and the results thereof, and submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; and other risks concerning Praxis’ programs and operations as described in its Annual Report on Form 10-K for the year ended December 31, 2024, its Quarterly Report on Form 10-Q for the quarter ended June 30, 2025 and other filings made with the Securities and Exchange Commission. Although Praxis’ forward-looking statements reflect the good faith judgment of Its management, these statements are based only on information and factors currently known by Praxis. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Praxis undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.
Investor Contact: Praxis Precision Medicines investors@praxismedicines.com 857-702-9452 Media Contact: Dan Ferry Life Science Advisors Daniel@lifesciadvisors.com 617-430-7576
FAQ
What did Praxis announce about relutrigine and the FDA on November 4, 2025 (PRAX)?
When is the EMBOLD cohort 2 interim analysis for PRAX-562 (relutrigine) planned?
What statistical thresholds will Praxis use for the interim and final EMBOLD analyses?
What were the EMBOLD cohort 1 results referenced by Praxis (PRAX)?
How does the EMERALD trial relate to Praxis’ relutrigine regulatory plan (PRAX)?
How many US patients live with SCN2A/SCN8A DEEs as noted by Praxis (PRAX)?
