Stoke Therapeutics Presents Zorevunersen Data Showing Substantial Reductions in Seizures and Improvements in Multiple Measures of Cognition and Behavior That Support the Potential for Disease Modification in Dravet Syndrome
Stoke Therapeutics (NASDAQ: STOK) presented promising data on zorevunersen (STK-001) for Dravet syndrome at the 15th European Epilepsy Congress. Key findings include:
1. Substantial seizure reductions: 85% median reduction at 3 months and 74% at 6 months after treatment.
2. Improvements in cognition and behavior within the first year of treatment, with additional increases as treatment continued.
3. Generally well-tolerated across studies.
4. Natural history study showed high seizure rates and developmental plateaus in Dravet patients despite standard treatments.
These results support zorevunersen's potential as the first disease-modifying treatment for Dravet syndrome, paving the way for a Phase 3 registrational study.
Stoke Therapeutics (NASDAQ: STOK) ha presentato dati promettenti su zorevunersen (STK-001) per la sindrome di Dravet al 15° Congresso Europeo sull'Epilessia. I risultati chiave includono:
1. Riduzioni sostanziali delle crisi: riduzione media del 85% a 3 mesi e del 74% a 6 mesi dopo il trattamento.
2. Miglioramenti nella cognizione e nel comportamento entro il primo anno di trattamento, con ulteriori aumenti man mano che il trattamento continuava.
3. Generalmente ben tollerato in tutti gli studi.
4. Uno studio sulla storia naturale ha mostrato alte frequenze di crisi e plateau nello sviluppo nei pazienti con Dravet nonostante i trattamenti standard.
Questi risultati supportano il potenziale di zorevunersen come primo trattamento modificante la malattia per la sindrome di Dravet, aprendo la strada a uno studio registrativo di Fase 3.
Stoke Therapeutics (NASDAQ: STOK) presentó datos prometedores sobre zorevunersen (STK-001) para el síndrome de Dravet en el 15º Congreso Europeo de Epilepsia. Los hallazgos clave incluyen:
1. Reducciones sustanciales de las crisis: reducción mediana del 85% a los 3 meses y del 74% a los 6 meses después del tratamiento.
2. Mejoras en la cognición y el comportamiento dentro del primer año de tratamiento, con incrementos adicionales a medida que continuaba el tratamiento.
3. Generalmente bien tolerado en todos los estudios.
4. Un estudio de historia natural mostró altas tasas de crisis y mesetas en el desarrollo en pacientes con Dravet a pesar de los tratamientos estándar.
Estos resultados respaldan el potencial de zorevunersen como el primer tratamiento modificador de la enfermedad para el síndrome de Dravet, allanando el camino para un estudio registrativo de Fase 3.
스톡 테라퓨틱스 (NASDAQ: STOK)는 제15회 유럽 간질 학회에서 드라베 증후군에 대한 조레부렌센( STK-001)의 유망한 데이터를 발표했습니다. 주요 결과는 다음과 같습니다:
1. 상당한 발작 감소: 치료 후 3개월에 85%, 6개월에 74%의 중간 감소.
2. 치료 첫 해에 인지 및 행동 개선이 있었으며, 치료가 계속될수록 추가적인 개선이 이루어졌습니다.
3. 연구 전반에 걸쳐 일반적으로 잘 견딥니다.
4. 자연사 연구는 표준 치료에도 불구하고 드라베 환자에서 높은 발작 비율과 발달 정체을 보여주었습니다.
이 결과는 드라베 증후군에 대한 최초의 질병 수정 치료제로서 조레부렌센의 잠재력을 뒷받침하며, 3상 등록 연구를 위한 길을 열어줍니다.
Stoke Therapeutics (NASDAQ: STOK) a présenté des données prometteuses sur le zorevunersen (STK-001) pour le syndrome de Dravet lors du 15ème Congrès Européen sur l’Épilepsie. Les résultats clés comprennent :
1. Réductions substantielles des crises : diminution médiane de 85% à 3 mois et de 74% à 6 mois après le traitement.
2. Améliorations de la cognition et du comportement au cours de la première année de traitement, avec des augmentations supplémentaires à mesure que le traitement se poursuivait.
3. Généralement bien toléré dans les études.
4. Une étude sur l'histoire naturelle a montré des taux de crises élevés et des plateaux développementaux chez les patients Dravet malgré les traitements standards.
Ces résultats soutiennent le potentiel du zorevunersen en tant que premier traitement modifiant la maladie pour le syndrome de Dravet, ouvrant la voie à une étude d'enregistrement de Phase 3.
Stoke Therapeutics (NASDAQ: STOK) präsentierte vielversprechende Daten zu Zorevunersen (STK-001) für das Dravet-Syndrom auf dem 15. Europäischen Epilepsiekongress. Die wichtigsten Erkenntnisse sind:
1. Erhebliche Anfallsreduktionen: Medianreduktion von 85% nach 3 Monaten und 74% nach 6 Monaten nach der Behandlung.
2. Verbesserungen der kognitiven Fähigkeiten und des Verhaltens innerhalb des ersten Behandlungsjahres, mit weiteren Zunahmen im Verlauf der Therapie.
3. Im Allgemeinen gut verträglich in den Studien.
4. Eine naturhistorische Studie zeigte hohe Anfallshäufigkeiten und Entwicklungsplateaus bei Dravet-Patienten trotz Standardbehandlungen.
Diese Ergebnisse unterstützen das Potenzial von Zorevunersen als erste krankheitsmodifizierende Therapie für das Dravet-Syndrom und ebnen den Weg für eine Phase-3-Registerstudie.
- Zorevunersen showed 85% median seizure reduction at 3 months and 74% at 6 months after treatment
- Meaningful improvements in cognition and behavior observed within the first year of treatment
- Durable reductions in convulsive seizure frequency observed throughout the course of treatment
- Data supports zorevunersen's potential as the first disease-modifying treatment for Dravet syndrome
- Results provide confidence for proceeding with Phase 3 registrational study
- Greater incidence of cerebrospinal fluid protein elevation observed in open-label extension studies
The data presented on zorevunersen for Dravet syndrome is highly promising and potentially game-changing. Key findings include:
- Substantial seizure reductions:
85% median reduction at 3 months and74% at 6 months post-treatment. - Improvements in cognition and behavior, a first for Dravet syndrome treatments.
- Generally well-tolerated safety profile.
These results suggest zorevunersen could be the first disease-modifying therapy for Dravet syndrome, addressing both seizures and developmental issues. The sustained effects and potential for improved outcomes with continued treatment are particularly encouraging. However, we must await Phase 3 results for confirmation of efficacy and long-term safety.
The zorevunersen data represents a potential paradigm shift in Dravet syndrome treatment. Current therapies only manage symptoms, leaving patients with high seizure rates and developmental delays. Zorevunersen's ability to reduce seizures by up to
This data significantly de-risks Stoke Therapeutics' lead program and bolsters its long-term growth prospects. Key financial implications:
- Increased probability of Phase 3 success and eventual FDA approval.
- Potential for premium pricing given the unprecedented efficacy in both seizure control and developmental outcomes.
- Expanded market opportunity beyond current Dravet syndrome treatments.
- Validation of Stoke's TANGO platform, potentially applicable to other genetic disorders.
While profitability is still years away, this data should strengthen Stoke's position for partnerships or financing. Investors should monitor Phase 3 progress and cash runway, but the risk-reward profile has notably improved.
– New data showed improvements in cognition and behavior during the first year of treatment with additional increases demonstrated as treatment continued –
– Clinical effects observed across the Phase 1/2a and open-label extension studies (OLEs) of zorevunersen are a first in the treatment of Dravet syndrome and support plans for the Company’s Phase 3 registrational study –
– Zorevunersen generally well-tolerated across the studies –
– Data presented for the first time at the 15th European Epilepsy Congress (EEC) –
Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures beginning within the first year of life. The disease is classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease. There are no approved disease-modifying therapies for people living with Dravet syndrome, which occurs in one out of 16,000 babies.
“The profound reductions in seizures and improvements in cognition and behavior seen in these studies open the door to a new era in the treatment of Dravet syndrome and provide convincing evidence of the potential for zorevunersen as the first disease-modifying medicine,” said Helen Cross, MB ChB, Ph.D., Professor, The Prince of Wales’s Chair of Childhood Epilepsy and Director of University College London Great Ormond Street Institute of Child Health, Honorary Consultant in Paediatric Neurology, and the ADMIRAL study lead investigator. “We are very encouraged by the data from the Phase 1/2a ADMIRAL study that showed substantial reductions in seizures and meaningful improvements in cognition and behavior within the first year of treatment. As patients continue treatment in the open-label extension study we see even greater improvements in their cognition and behavior, which is remarkable.”
“The two-year natural history data provide clear evidence that current anti-seizure medicines are insufficient because even with the best available medicines patients still suffer from continued high rates of seizures and, as these children age, their development falls further behind their neurotypical peers,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “Data from our clinical studies of zorevunersen provide a glimpse into the future of treatment for patients with Dravet syndrome. The data from our studies suggest that by restoring protein expression with zorevunersen, we may be able to substantially reduce seizures beyond any benefit patients are currently receiving from anti-seizure medicines. Even more promising is the potential to improve cognition and behavior, which has never before been demonstrated in a clinical study of Dravet syndrome. These data provide confidence in our plans for a Phase 3 registrational study, including the dose regimen and clinical endpoints.”
Highlights from the Company’s presentations at the meeting include:
-
MONARCH and ADMIRAL Phase 1/2a studies [Paediatric Epileptology Session: Tuesday, September 10 at 12:22PM CEST]: Single and multiple doses of zorevunersen up to 70mg were generally well tolerated. Patients treated with 2 or 3 doses of 70mg of zorevunersen experienced median seizure reductions of
85% (n=10) at 3 months and74% (n=9) at 6 months after the last dose, compared to baseline. Multiple doses of zorevunersen (30mg, 45mg, or 70mg) led to meaningful improvements in multiple measures of cognition and behavior within the first year of treatment, including receptive communication, interpersonal relationships and gross motor skills.
- SWALLOWTAIL and LONGWING open label extension (OLE) studies [Poster: P875]: Safety findings among patients who continued treatment were consistent with the findings from the Phase 1/2a studies, except for a greater incidence of cerebrospinal fluid protein elevation. Durable reductions in convulsive seizure frequency were observed throughout the course of treatment. In addition, data indicated meaningful improvements in multiple measures of cognition and behavior over the first year of continued dosing of zorevunersen.
- BUTTERFLY (natural history study) [Poster: P788]: Compared to their neurotypical peers, adaptive functioning and neurodevelopment in patients with Dravet syndrome generally plateaued, resulting in a widening developmental gap over time. Seizure rates remained high over 24 months despite treatment with standard-of-care antiseizure medications.
All presentations are available for download on the Stoke Therapeutics website under the Investors & News tab.
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 (STK-001)
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, and rare pediatric disease designation by the FDA as a potential new treatment for Dravet syndrome.
About the
The MONARCH study was a Phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study were to assess the safety and tolerability of zorevunersen (STK-001), as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective was to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency.
Following completion of MONARCH, patients who met study entry criteria were eligible to continue treatment in SWALLOWTAIL, an open-label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of zorevunersen. The study is also evaluating the long-term effects of zorevunersen on convulsive seizure frequency and on behavior, cognition and overall quality of life. Dosing in SWALLOWTAIL is ongoing.
About the
The ADMIRAL study was a Phase 1/2a open-label study of children and adolescents ages 2 to <18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study were to assess the safety and tolerability of multiple doses of zorevunersen (STK-001), as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective was to assess the effect of multiple doses of zorevunersen as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Overall clinical status and quality of life were secondary endpoints of ADMIRAL.
Following completion of ADMIRAL, patients who met study entry criteria were eligible to continue treatment in LONGWING, an open-label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of zorevunersen. The study is also evaluating the long-term effects of zorevunersen on convulsive seizure frequency and on behavior, cognition and overall quality of life. Dosing in LONGWING is ongoing.
About the BUTTERFLY Observational Study
The BUTTERFLY study was a multicenter, longitudinal, prospective, observational study of children and adolescents ages 2 to 18 who have been diagnosed with Dravet syndrome as a result of an SCN1A gene mutation. This study was designed to evaluate neurodevelopmental status and change from baseline to 24 months. Secondary and exploratory endpoints in the study evaluated changes in other disease measures, including seizures and additional non-seizure comorbidities. No investigational medications or other treatments were provided. Participants continued to receive their usual care, including anti-seizure medications, and were observed for up to two years. The study was conducted at approximately 20 sites in
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 non-seizure comorbidities and the timing and expected progress of clinical trials, regulatory meetings and regulatory decisions. 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 of, and ultimately commercialize its product candidates, including zorevunersen; the timing of data readouts and interim and final results of preclinical 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 stage clinical trials may not be predictive of results in later stage trials; the Company’s ability to fund development activities and achieve development goals; 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 and 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, Inc.
FAQ
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