Stoke Therapeutics Presents New Open-Label Extension (OLE) Study Data That Further Support the Potential for Zorevunersen as a Disease-Modifying Medicine for the Treatment of Dravet Syndrome
Stoke Therapeutics (NASDAQ: STOK) announced new data from studies of zorevunersen for Dravet syndrome treatment. Nine patients treated with 2-3 doses of 70mg followed by 45mg maintenance dosing showed substantial seizure reductions, with an 87% median reduction at month eight. Patients demonstrated continuous improvements in cognition and behavior through 2 years of treatment.
The drug was generally well-tolerated across Phase 1/2a and OLE studies, with 81 patients treated. Safety findings showed 30% experienced treatment-related adverse events, mainly CSF protein elevations and procedural vomiting. The data support the company's proposed Phase 3 registrational study regimen.
Stoke Therapeutics (NASDAQ: STOK) ha annunciato nuovi dati provenienti da studi su zorevunersen per il trattamento della sindrome di Dravet. Nove pazienti trattati con 2-3 dosi di 70mg seguite da una dose di mantenimento di 45mg hanno mostrato riduzioni significative delle crisi, con una riduzione mediana dell'87% al mese otto. I pazienti hanno dimostrato miglioramenti continui in cognizione e comportamento nel corso di 2 anni di trattamento.
Il farmaco è stato generalmente ben tollerato negli studi di Fase 1/2a e OLE, con 81 pazienti trattati. I risultati sulla sicurezza hanno mostrato che il 30% dei pazienti ha sperimentato eventi avversi correlati al trattamento, principalmente elevazioni delle proteine nel liquido cerebrospinale e vomito procedurale. I dati supportano il regime proposto dalla compagnia per lo studio registrativo di Fase 3.
Stoke Therapeutics (NASDAQ: STOK) anunció nuevos datos de estudios sobre zorevunersen para el tratamiento del síndrome de Dravet. Nueve pacientes tratados con 2-3 dosis de 70mg seguidas de una dosis de mantenimiento de 45mg mostraron reducciones sustanciales de las convulsiones, con una reducción mediana del 87% en el mes ocho. Los pacientes demostraron mejoras continuas en cognición y comportamiento a lo largo de 2 años de tratamiento.
El medicamento fue generalmente bien tolerado en los estudios de Fase 1/2a y OLE, con 81 pacientes tratados. Los hallazgos de seguridad mostraron que el 30% experimentó eventos adversos relacionados con el tratamiento, principalmente elevaciones de proteínas en el líquido cefalorraquídeo y vómitos procedimentales. Los datos respaldan el régimen propuesto por la compañía para el estudio registracional de Fase 3.
스톡 테라퓨틱스(NASDAQ: STOK)는 드라베 증후군 치료를 위한 조레부넬센에 대한 연구에서 새로운 데이터를 발표했습니다. 70mg의 2-3회 용량과 45mg 유지 용량으로 치료된 9명의 환자는 유의미한 발작 감소를 보였으며, 8개월 차에 중간 발작 감소율이 87%에 달했습니다. 환자들은 2년의 치료 기간 동안 인지 및 행동에서 지속적인 개선을 보였습니다.
약물은 1/2a 단계 및 OLE 연구에서 전반적으로 잘 견딜 수 있는 것으로 나타났으며, 81명의 환자가 치료를 받았습니다. 안전성 결과에 따르면, 30%가 치료와 관련된 부작용을 경험했으며, 주로 뇌척수액 단백질 상승과 절차적 구토가 있었습니다. 데이터는 회사가 제안한 3상 등록 연구 계획을 뒷받침합니다.
Stoke Therapeutics (NASDAQ: STOK) a annoncé de nouvelles données provenant d'études sur le zorevunersen pour le traitement du syndrome de Dravet. Neuf patients traités avec 2-3 doses de 70 mg suivies d'une dose d'entretien de 45 mg ont montré des réductions significatives des crises, avec une réduction médiane de 87% au mois huit. Les patients ont démontré des améliorations continues en cognition et comportement pendant 2 ans de traitement.
Le médicament a été généralement bien toléré dans les études de Phase 1/2a et OLE, avec 81 patients traités. Les résultats de sécurité ont montré que 30% ont subi des événements indésirables liés au traitement, principalement des élévations de protéines dans le liquide céphalorachidien et des vomissements procéduraux. Les données soutiennent le régime proposé par la société pour l'étude d'enregistrement de Phase 3.
Stoke Therapeutics (NASDAQ: STOK) hat neue Daten aus Studien zu Zorevunersen zur Behandlung des Dravet-Syndroms veröffentlicht. Neun Patienten, die mit 2-3 Dosen von 70 mg gefolgt von 45 mg Erhaltungsdosis behandelt wurden, zeigten signifikante Anfallsreduktionen mit einer mittleren Reduktion von 87% im achten Monat. Die Patienten zeigten über einen Zeitraum von 2 Jahren kontinuierliche Verbesserungen in Kognition und Verhalten.
Das Medikament war in den Phase 1/2a und OLE Studien im Allgemeinen gut verträglich, wobei 81 Patienten behandelt wurden. Sicherheitsbefunde zeigten, dass 30% behandlungsbedingte Nebenwirkungen erlebten, hauptsächlich erhöhte Proteine im Liquor cerebrospinalis und prozeduralen Erbrechen. Die Daten stützen das von dem Unternehmen vorgeschlagene Regime für die Phase 3 Zulassungsstudie.
- 87% median reduction in seizures at month eight post-treatment
- Sustained 50% or greater median reduction in seizures throughout the study
- Continuous improvements in cognition and behavior through 2 years
- 82% (61/74) patient retention rate in OLE studies
- Data supports advancement to Phase 3 trials
- 30% of patients experienced treatment-related adverse events
- 79% of OLE patients showed elevated CSF protein levels
- One patient discontinued treatment due to elevated CSF protein
- 22% of patients had treatment-emergent serious adverse events
Insights
The latest data from Stoke Therapeutics' zorevunersen trials shows compelling evidence of its potential as a disease-modifying treatment for Dravet syndrome. The
The continuous improvements in cognition and behavior through 2 years of treatment are particularly noteworthy, as current anti-seizure medications typically don't address these aspects of the disease. The safety profile appears manageable, with most adverse events being procedural or monitorable (CSF protein elevations). The EEG data showing sustained reduction in slow-wave activity provides objective evidence of the drug's central nervous system impact.
This data release significantly strengthens zorevunersen's commercial potential. The 82% retention rate in the open-label extension studies indicates strong patient satisfaction, while the durability of response suggests a competitive advantage over existing treatments. The validation of Vineland-3 scale improvements as clinically meaningful to caregivers provides important support for the drug's value proposition.
For investors, the timing is important as Stoke approaches Phase 3 trials. The comprehensive data package, including both seizure control and cognitive improvements, could support premium pricing if approved. With a relatively modest market cap of
– Substantial and durable reductions in convulsive seizure frequency observed in patients treated with 2 or 3 doses of 70mg followed by 45mg maintenance dosing on top of the best available anti-seizure medicines –
– Patients experienced continuous improvements in multiple measures of cognition and behavior with ongoing treatment through 2 years –
– Data support proposed Phase 3 registrational study regimen; Update anticipated before year-end –
– Zorevunersen generally well-tolerated across the studies –
– Data to be presented at the American Epilepsy Society (AES) 2024 Annual Meeting; Company to host virtual event for investors and analysts on Monday, December 9 at 8:30 am Eastern (5:30 am Pacific) –
Figure 1. Substantial and Durable Reductions in Convulsive Seizure Frequency from Baseline in Patients who Received 70mg zorevunersen in Phase 1/2a (Graphic: Business Wire)
The company will host a virtual educational event for investors and research analysts on Monday, December 9 at 8:30 am Eastern (5:30 am Pacific).
“Dravet syndrome is stressful to live with and challenging to treat. Anti-seizure medicines are helpful in reducing seizures but can only do so much for patients who continue to experience significant and life-altering limitations in many aspects of neurodevelopment and daily living,” said Joseph Sullivan, M.D., FAES, Professor of Neurology and Pediatrics and Director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco. “The substantial and durable reductions in seizures, as well as the continuous gains in multiple measures of behavior and cognition through 2 years in patients treated in these studies have never been seen before in studies of Dravet syndrome. I am encouraged by these data and convinced that we are on the verge of a new era in the treatment of this disease.”
“The new long-term data give us a more complete and convincing picture of the potential for zorevunersen as a disease-modifying medicine,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “Patients entered our studies with high seizure rates despite being treated with the best available anti-seizure medicines. The durability of the substantial reductions in their seizures, particularly among those treated with initial doses of 70mg are remarkable and support a highly differentiated mechanism of action for zorevunersen. These data, combined with the continuous improvements in cognition and behavior, are highly supportive of our plans to conduct a Phase 3 study and the dose regimen currently under discussion with global regulatory agencies.”
Key Study Finding: Substantial and Durable Reductions in Convulsive Seizure Frequency
Poster 2.379 and 2.364
Previously reported end-of-Phase 1/2a study data from patients treated with two or three doses of 70mg of zorevunersen showed substantial and sustained reductions in convulsive seizure frequency of
The Company is now reporting data for the nine patients who continued treatment with at least two doses of 45mg of zorevunersen in the OLE study. These patients sustained at least a
Key Study Finding: Continuous Improvements in Multiple Measures of Cognition and Behavior
Patients experienced continuous improvements in multiple measures of cognition and behavior as measured by the Vineland-3 through 2 years of treatment with ongoing maintenance dosing in the OLEs. Additional improvements were indicated within the first nine months of treatment among patients in the Phase 1/2a ADMIRAL study. See Figure 2.
Key Safety Findings
At the time of the analysis, 81 patients had been treated with zorevunersen in the Phase 1/2a studies. Seventy-four patients who completed the Phase 1/2a studies and were eligible enrolled in the OLEs. As of June 2024,
- Zorevunersen was generally well-tolerated across the Phase 1/2a and OLE studies.
-
In the Phase 1/2a studies:
-
30% (24/81) of patients experienced a treatment-emergent adverse event (TEAE) that was related to study drug. The most common were CSF protein elevations and procedural vomiting; and -
22% (18/81) of patients had a treatment-emergent serious adverse event. These events were assessed as unrelated to study drug except for the previously reported case of one patient who experienced Suspected Unexpected Serious Adverse Reactions (SUSARs).
-
-
A greater incidence of CSF protein elevation was observed in the OLEs.
79% (56/71) of patients in the OLEs had at least 1 CSF protein value >50 mg/dL. No clinical manifestations have been observed in these patients. - Across the studies, one patient discontinued treatment due to study drug. As previously reported, this patient discontinued treatment in the OLE due to elevated CSF protein.
Additional Presentations
Small Changes on the Vineland-3 are Meaningful to Caregivers of Patients with Dravet Syndrome
Poster: 3.383
The Company will also present the results of a study of caregivers and clinical experts that was designed to evaluate what constitutes meaningful change on the Vineland-3 and to generate insight into caregiver perceptions of the key signs, symptoms and impacts of Dravet syndrome. The study found that small changes in adaptive behavior, as measured by the Vineland-3, are considered clinically meaningful by both caregivers of patients with Dravet syndrome and clinical experts. Changes of 2 to 3 points in growth scale values across subdomains were considered meaningful by at least
Spectral EEG Analysis Demonstrates Decreased Slow-wave Activity in Patients with Dravet Syndrome after Treatment with Zorevunersen, an Antisense Oligonucleotide
Poster: 3.407
An EEG analysis of 74 patients treated in clinical studies of zorevunersen showed a reduction in slow-wave activity following zorevunersen administration. The treatment effect on spectral power is most pronounced at the highest zorevunersen doses, with reductions in slow-wave activity sustained for months after the last dose. Topographical spectral changes indicate that zorevunersen produces a widespread and durable effect across the brain.
All presentations are available for download on the Stoke Therapeutics website under the Investors & News tab.
Stoke Therapeutics Analyst and Investor Virtual Event
Stoke will host a virtual event with discussions led by leading clinicians and patient advocates to offer analysts and investors an opportunity to learn more about Dravet syndrome, its overall effects, and the potential real-world impacts of a disease-modifying medicine. As part of this event, the clinicians are expecting to share anecdotes and visuals from their experience treating patients in the clinical studies of zorevunersen.
Title: Understanding Dravet Syndrome: The Unmet Need and Potential for Disease-Modification
Date and Time: Monday, December 9, 8:30-9:30 AM EST (5:30-6:30 AM PST)
Presenters: Edward M. Kaye, M.D., CEO of Stoke Therapeutics, Joseph Sullivan, M.D., FAES, Professor of Neurology and Pediatrics and Director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco; Andreas Brunklaus M.D., Consultant Paediatric Neurologist at the Royal Hospital for Children,
Webcast Link: https://edge.media-server.com/mmc/p/bv6h2oxs
About Dravet Syndrome
Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. 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. The effects of the disease go beyond seizures and 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. The disease is classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease. 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 out of 16,000 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 1955, including, but not limited to: the ability of zorevunersen (STK-001) to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior or cognition at the indicated dosing levels or at all; the timing and expected progress of clinical trials, data readouts, regulatory decisions and other presentations for zorevunersen, including the timing and presentation of data at AES 2024; the potential for zorevunersen to be the first disease-modifying therapy for Dravet syndrome; the timing of regulatory interactions or the outcomes thereof; our expectations, plans, aspirations and goals, including those related to the potential of zorevunersen. Statements including words such as "anticipate," "believe," "hope," "plan," "will," "continue," expect," "ongoing," or "potential" 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: our ability to advance, obtain regulatory approval of, and ultimately commercialize our product candidates, including zorevunersen; the timing of data readouts and interim and final results of nonclinical and clinical trials; nonclinical and clinical data are voluminous and detailed, and regulatory authorities may interpret or weigh the importance of data differently and reach different conclusions than us or others, request additional information, have additional recommendations or change their guidance or requirements before or after approval; receiving Breakthrough Therapy Designation may not lead to a faster development or regulatory review or approval and does not mean zorevunersen will receive marketing approval; our ability to fund development activities and achieve development goals; our ability to protect our intellectual property; 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 and volatile market conditions, and global events, including public health crises and ongoing geopolitical conflicts, such as the conflicts in
View source version on businesswire.com: https://www.businesswire.com/news/home/20241206101127/en/
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, Inc.
FAQ
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