Stoke Therapeutics Announces Alignment with Global Regulatory Agencies and Plans to Initiate a Phase 3 Study of Zorevunersen as Potentially the First Disease-Modifying Medicine for the Treatment of Dravet Syndrome
Stoke Therapeutics (Nasdaq: STOK) has achieved alignment with FDA, EMA, and PMDA for its Phase 3 EMPEROR study of zorevunersen, potentially the first disease-modifying treatment for Dravet syndrome. The study will evaluate two loading doses of 70mg followed by two maintenance doses of 45mg over 52 weeks versus sham in patients aged 2 to <18 years.
The primary endpoint will measure reduction in major motor seizure frequency, while key secondary endpoints include improvements in cognition and behavior. Recent clinical data showed an 87% median reduction in convulsive seizure frequency at month eight in treated patients. The Phase 3 study, planned to start in mid-2025, will enroll approximately 150 patients globally, with data expected by end of 2027.
Zorevunersen has received FDA Breakthrough Therapy Designation, which may expedite development and review. The treatment has been generally well tolerated, with over 600 doses administered to patients, some remaining on treatment for more than three years.
Stoke Therapeutics (Nasdaq: STOK) ha raggiunto un accordo con la FDA, l'EMA e la PMDA per il suo studio di Fase 3 EMPEROR relativo a zorevunersen, che potrebbe rappresentare il primo trattamento modificante la malattia per la sindrome di Dravet. Lo studio valuterà due dosi di carico di 70 mg seguite da due dosi di mantenimento di 45 mg nell'arco di 52 settimane, rispetto a un placebo, in pazienti di età compresa tra 2 e <18 anni.
L'endpoint primario misurerà la riduzione della frequenza delle crisi motorie maggiori, mentre gli endpoint secondari chiave includono miglioramenti nella cognizione e nel comportamento. Dati clinici recenti hanno mostrato una riduzione mediana dell'87% nella frequenza delle crisi convulsive dopo otto mesi nei pazienti trattati. Lo studio di Fase 3, previsto per iniziare a metà 2025, arruolerà circa 150 pazienti a livello globale, con dati attesi entro la fine del 2027.
Zorevunersen ha ricevuto la Designazione di Terapia Innovativa dalla FDA, il che potrebbe accelerare lo sviluppo e la revisione. Il trattamento è stato generalmente ben tollerato, con oltre 600 dosi somministrate a pazienti, alcuni dei quali sono rimasti in trattamento per più di tre anni.
Stoke Therapeutics (Nasdaq: STOK) ha logrado un acuerdo con la FDA, la EMA y la PMDA para su estudio de Fase 3 EMPEROR sobre zorevunersen, que podría ser el primer tratamiento modificador de la enfermedad para el síndrome de Dravet. El estudio evaluará dos dosis de carga de 70 mg seguidas de dos dosis de mantenimiento de 45 mg durante 52 semanas en comparación con un placebo en pacientes de 2 a <18 años.
El punto final primario medirá la reducción en la frecuencia de las crisis motoras mayores, mientras que los puntos finales secundarios clave incluyen mejoras en la cognición y el comportamiento. Datos clínicos recientes mostraron una reducción mediana del 87% en la frecuencia de crisis convulsivas al mes ocho en los pacientes tratados. El estudio de Fase 3, planeado para comenzar a mediados de 2025, inscribirá aproximadamente a 150 pacientes a nivel mundial, con datos esperados para finales de 2027.
Zorevunersen ha recibido la Designación de Terapia Innovadora de la FDA, lo que puede acelerar el desarrollo y la revisión. El tratamiento ha sido generalmente bien tolerado, con más de 600 dosis administradas a pacientes, algunos de los cuales han permanecido en tratamiento por más de tres años.
Stoke Therapeutics (Nasdaq: STOK)는 zorevunersen의 3상 EMPEROR 연구에 대해 FDA, EMA, PMDA와 합의를 도달했습니다. 이 연구는 드라베 증후군에 대한 첫 번째 질병 수정 치료제가 될 수 있습니다. 연구는 2세에서 <18세> 이하의 환자를 대상으로 52주 동안 70mg의 로딩 용량 두 번과 45mg의 유지 용량 두 번을 위약과 비교하여 평가할 것입니다.
주요 목표는 주요 운동 발작 빈도의 감소를 측정하고, 주요 이차 목표에는 인지 및 행동 개선이 포함됩니다. 최근의 임상 데이터에 따르면 치료 받은 환자의 8개월째에는 발작의 빈도가 중앙값 87% 감소했습니다. 2025년 중반에 시작될 계획인 3상 연구는 전 세계적으로 약 150명의 환자를 모집할 예정이며, 2027년 말까지 데이터를 기대하고 있습니다.
Zorevunersen은 FDA의 혁신 치료제 지정을 받았으며, 이는 개발 및 검토를 가속화할 수 있습니다. 이 치료법은 일반적으로 잘 견뎌졌으며, 600회 이상의 용량이 환자에게 투여되어 일부는 3년 이상 치료를 받았습니다.
Stoke Therapeutics (Nasdaq: STOK) a atteint un accord avec la FDA, l'EMA et la PMDA pour son étude de phase 3 EMPEROR portant sur zorevunersen, qui pourrait représenter le premier traitement modifiant la maladie pour le syndrome de Dravet. L'étude évaluera deux doses de chargement de 70 mg suivies de deux doses d'entretien de 45 mg sur 52 semaines par rapport à un placebo chez des patients âgés de 2 à <18 ans.
L'objectif principal mesurera la réduction de la fréquence des crises motrices majeures, tandis que les principaux objectifs secondaires incluent des améliorations de la cognition et du comportement. Des données cliniques récentes ont montré une réduction médiane de 87 % de la fréquence des crises convulsives à huit mois chez les patients traités. L'étude de phase 3, prévue pour débuter à mi-2025, recrutera environ 150 patients au niveau mondial, avec des données attendues d'ici fin 2027.
Zorevunersen a reçu la désignation de thérapie révolutionnaire par la FDA, ce qui pourrait accélérer le développement et l'examen. Le traitement a généralement été bien toléré, avec plus de 600 doses administrées à des patients, certains restant sous traitement pendant plus de trois ans.
Stoke Therapeutics (Nasdaq: STOK) hat eine Vereinbarung mit der FDA, EMA und PMDA für seine Phase 3 EMPEROR-Studie zu zorevunersen erreicht, das möglicherweise die erste krankheitsmodifizierende Behandlung für das Dravet-Syndrom sein könnte. Die Studie wird zwei Ladedosen von 70 mg gefolgt von zwei Erhaltungsdosen von 45 mg über 52 Wochen im Vergleich zu einem Placebo bei Patienten im Alter von 2 bis <18 Jahren bewerten.
Der primäre Endpunkt wird die Reduktion der Häufigkeit von schweren motorischen Anfällen messen, während die wichtigsten sekundären Endpunkte Verbesserungen in der Kognition und im Verhalten umfassen. Jüngste klinische Daten zeigten eine mediane Reduktion von 87 % in der Häufigkeit von krampfartigen Anfällen nach acht Monaten bei behandelten Patienten. Die Phase-3-Studie, die für Mitte 2025 geplant ist, wird voraussichtlich etwa 150 Patienten weltweit einschreiben, mit Ergebnissen, die bis Ende 2027 erwartet werden.
Zorevunersen hat die Zulassung als Durchbruchtherapie von der FDA erhalten, die den Entwicklungs- und Überprüfungsprozess beschleunigen kann. Die Behandlung wurde allgemein gut vertragen, mit über 600 verabreichten Dosen an Patienten, einige erhielten die Behandlung länger als drei Jahre.
- 87% median reduction in convulsive seizure frequency demonstrated in clinical trials
- FDA Breakthrough Therapy Designation received
- Over 600 doses administered with good tolerability
- Alignment achieved with three major global regulatory agencies
- Phase 3 study won't start until mid-2025
- Final data not expected until end of 2027
Insights
The alignment with major regulatory agencies (FDA, EMA, PMDA) for zorevunersen's Phase 3 EMPEROR study represents a critical milestone in Dravet syndrome treatment development. The FDA Breakthrough Therapy designation significantly accelerates the development timeline and indicates strong preliminary efficacy data.
The existing clinical data is particularly compelling, showing an
The Phase 3 study design, targeting approximately 150 patients, is well-powered to demonstrate efficacy. The inclusion of both seizure reduction and cognitive/behavioral endpoints positions zorevunersen as potentially the first disease-modifying treatment for Dravet syndrome, addressing both symptoms and underlying disease mechanisms.
For STOK, with a market cap of
The planned mid-2025 study initiation with data expected by end-2027 provides a clear catalyst timeline for investors. The comprehensive endpoint strategy, addressing both seizure control and quality of life measures, could support premium pricing if approved. The potential first-mover advantage in disease modification for Dravet syndrome represents a substantial market opportunity, considering current treatments only address symptoms.
The dosing regimen (two 70mg loading doses followed by 45mg maintenance doses) demonstrates sophisticated pharmacological strategy. The durability of response, with effects maintained through maintenance dosing, suggests potential for long-term disease modification. The inclusion of Vineland-3, BSID-IV and global impression scales provides comprehensive assessment of treatment impact beyond seizure control.
The study's focus on patients with confirmed SCN1A variants ensures a well-defined patient population. The age range (2 to <18 years) is particularly relevant as early intervention may maximize therapeutic benefit. The global study approach enhances result generalizability and supports simultaneous regulatory submissions across major markets.
– Alignment achieved with
– One-year study of zorevunersen will evaluate reductions in major motor seizure frequency as well as improvements in behavior and cognition in children and adolescents ages 2 to <18 years old –
– FDA Breakthrough Therapy designation positions zorevunersen on efficient development path; Company plans to start Phase 3 in mid-2025 –
– Webcast and conference call for analysts and investors at 8:00AM Eastern Time today –
Following successful interactions with the FDA, EMA and PMDA, the Company has finalized its EMPEROR Phase 3 study protocol. The proposed study will evaluate two loading doses of 70mg followed by two maintenance doses of 45mg over 52-weeks compared to sham in children and adolescents ages 2 to <18 with Dravet syndrome. The primary endpoint will be reduction in major motor seizure frequency. Key secondary endpoints will include improvements in cognition and behavior as measured primarily by
“Alignment around a global Phase 3 study design for zorevunersen puts us one step closer to our goal of delivering the first disease-modifying medicine for the treatment of Dravet syndrome,” said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. “The level of attention and enthusiasm from clinicians, patient organizations and regulatory authorities for this study
speaks to the shared understanding that current treatments are inadequate. Their support also underscores a belief in the data from our clinical studies that demonstrated substantial and durable reductions in seizure frequency and improvements across multiple measures of cognition and behavior, when treated with a similar dosing regimen. We look forward to continuing to work together with a sense of purpose and urgency as we prepare to initiate the EMPEROR study by mid-year.”
“I have participated as an investigator in many clinical research studies, nearly all of which have been designed to test the next best anti-seizure medicine,” said Dr. Kelly Knupp, M.D., MSCS, Professor of Pediatrics and Neurology at the University of
Zorevunersen was recently granted FDA Breakthrough Therapy Designation, a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically-significant endpoint(s).
Clinical Data Support the Phase 3 Dosing Regimen
The Company recently presented data demonstrating that patients treated with two or three doses of 70mg in the Phase 1/2a study and two doses of 45mg in an open-label extension study (OLE), experienced an
Zorevunersen has been generally well tolerated across the studies. To date, more than 600 doses of zorevunersen have been administered to patients across multiple studies, with some patients remaining on treatment for more than three years.
EMPEROR Pivotal Phase 3 Design Summary
The pivotal Phase 3 study will be a global, randomized, double-blind, sham-controlled trial.
Anticipated Enrollment: Approximately 150 patients with Dravet syndrome between the ages of 2 to <18 years of age.
Diagnosis: A confirmed variant in the SCN1A gene not associated with a gain of function.
Primary Endpoint: Percent change from baseline in major motor seizure frequency in patients receiving zorevunersen as compared to sham.
Key Secondary Endpoints: Durability of effect on major motor seizure frequency. Improvements in behavior and cognition as measured by
Additional Endpoints: Safety, Clinician Global Impression of Change (CGI-C), Caregiver Global Impression of Change (CaGI-C), and the Bayley Scales of Infant Development (BSID-IV).
Global Participation: The study will be conducted in the
Duration: 60 weeks (8-week baseline period followed by 52-week treatment period)
Phase 3 Data: Data are anticipated by the end of 2027, pending enrollment and study timelines.
Continuing Treatment: Patients who are eligible will be offered ongoing treatment with zorevunersen as part of an OLE study.
Stoke Webcast and Conference Call for Analysts and Investors
Stoke management will host a webcast and conference call for analysts and investors on Tuesday, January 7, 2025, at 8:00am Eastern Time. The call will focus on the successful alignment with global regulatory agencies related to a Phase 3 study of zorevunersen. The webcast will be available on the Investors & News section of Stoke’s website at https://investor.stoketherapeutics.com/. Research analysts who plan to join the call and participate in the Q&A session may register here to receive the dial-in details and a unique PIN. All other participants are invited to access the listen-only webcast by clicking here. A replay of the webcast will be archived and available for at least 90 days following the event.
About Dravet Syndrome
Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE). Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Dravet syndrome is characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Beyond seizures, Dravet syndrome is associated with developmental and cognitive impairments that often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. There are no approved disease-modifying therapies for people living with Dravet syndrome. One in 15,600 babies are born with Dravet syndrome, which is not concentrated in a particular geographic area or ethnic group.
About Zorevunersen
Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. Stoke believes that zorevunersen, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. Zorevunersen is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Zorevunersen has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation, not associated with gain-of-function, in the SCN1A gene.
About Stoke Therapeutics
Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore protein levels. Stoke’s first compound, zorevunersen (STK-001), is in clinical testing for the treatment of Dravet syndrome, a severe and progressive genetic epilepsy. Dravet syndrome is one of many diseases caused by a haploinsufficiency, in which a loss of ~
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the ability of zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior and cognition at the indicated dosing levels or at all; the design, timing and results of the Phase 3 clinical trial; and the timing and expected progress of data readouts, regulatory meetings, regulatory decisions and other presentations. Statements including words such as “expect,” “plan,” “will,” “continue,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause our results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: the Company’s ability to advance, obtain regulatory approval or, and ultimately commercialize its product candidates, including zorevunersen; the timing of data readouts and interim and final results of nonclinical and clinical trials; the receipt and timing of potential regulatory decisions; positive results in a clinical trial may not be replicated in subsequent trials or successes in early state clinical trials may not be predictive of results in later stage trials; the Company’s ability to fund development activities and achieve development goals, including expectations regarding the Company’s collaboration with Acadia Pharmaceuticals; the Company’s ability to protect its intellectual property; the direct or indirect impact of global business, political and macroeconomic conditions, including inflation, interest rate volatility, cybersecurity events, uncertainty with respect to the federal budget, instability in the global banking system, volatile market conditions, and global events, including public health crises and ongoing geopolitical conflicts, such as the conflicts in
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Stoke Media & Investor Contacts:
Dawn Kalmar
Chief Communications Officer
dkalmar@stoketherapeutics.com
781-303-8302
Doug Snow
Director, Communications & Investor Relations
IR@stoketherapeutics.com
508-642-6485
Source: Stoke Therapeutics
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