Biohaven Presents New Data with BHV-7000 Once-Daily Extended-Release Formulation Demonstrating Excellent Safety Profile and Nonclinical Data Updates at American Epilepsy Society 2024 Annual Meeting
Biohaven presented expanded safety data for BHV-7000, their novel anti-seizure medication, at the American Epilepsy Society 2024 Annual Meeting. The Phase 1 multiple ascending dose studies demonstrated excellent tolerability of the once-daily extended-release formulation without typical CNS adverse effects associated with other anti-seizure medications.
The drug showed favorable safety at doses up to 120 mg daily for 15 days, exceeding the doses being evaluated in ongoing Phase 2/3 trials (up to 75 mg daily). Studies revealed low rates of CNS-related adverse events, with no somnolence or cognitive disturbances reported. Additional nonclinical data showed BHV-7000's effectiveness in reducing neuronal activity and rescuing current density in KCNQ2 variants.
Biohaven ha presentato dati di sicurezza ampliati per BHV-7000, il loro nuovo farmaco anti-crisi, durante l'Annual Meeting 2024 della American Epilepsy Society. Gli studi di fase 1 con dosi ascendenti multiple hanno dimostrato un'eccellente tollerabilità della formulazione a rilascio prolungato assunta una volta al giorno, senza gli effetti avversi tipici sul sistema nervoso centrale associati ad altri farmaci anti-crisi.
Il farmaco ha mostrato una sicurezza favorevole a dosi fino a 120 mg al giorno per 15 giorni, superando le dosi attualmente in fase di valutazione negli studi di fase 2/3 (fino a 75 mg al giorno). Gli studi hanno rivelato tassi bassi di eventi avversi correlati al sistema nervoso centrale, senza né sonnolenza né disturbi cognitivi segnalati. Dati non clinici aggiuntivi hanno dimostrato l'efficacia di BHV-7000 nella riduzione dell'attività neuronale e nel recupero della densità di corrente nelle varianti KCNQ2.
Biohaven presentó datos de seguridad ampliados para BHV-7000, su novedoso medicamento antiepiléptico, en la Reunión Anual de 2024 de la American Epilepsy Society. Los estudios de fase 1 con dosis ascendentes múltiples demostraron una excelente tolerabilidad de la formulación de liberación prolongada administrada una vez al día, sin los efectos adversos típicos del sistema nervioso central asociados a otros medicamentos antiepilépticos.
El fármaco mostró una seguridad favorable a dosis de hasta 120 mg diarios durante 15 días, superando las dosis que se están evaluando en ensayos de fase 2/3 (hasta 75 mg diarios). Los estudios revelaron tasas bajas de eventos adversos relacionados con el SNC, sin somnolencia ni alteraciones cognitivas reportadas. Datos no clínicos adicionales mostraron la eficacia de BHV-7000 en la reducción de la actividad neuronal y en la recuperación de la densidad de corriente en variantes de KCNQ2.
Biohaven은 2024년 미국 간질학회 연례 회의에서 그들의 새로운 항 경련제 BHV-7000에 대한 확장된 안전성 데이터를 발표했습니다. 1상 다중 상승 용량 연구는 다른 항 경련제와 관련된 일반적인 중추신경계 부작용 없이 하루에 한 번 복용하는 서방형 제형의 우수한 내약성을 보여주었습니다.
이 약물은 15일 동안 하루 120mg까지의 용량에서 유리한 안전성을 나타내었으며, 현재 진행 중인 2/3상 시험에서 평가되고 있는 최대 75mg의 용량을 초과합니다. 연구 결과 중추신경계 관련 부작용의 발생률이 낮고, 졸림이나 인지 장애가 보고되지 않았습니다. 추가 비임상 데이터는 KCNQ2 변이에 대한 BHV-7000의 신경 활동 감소 및 전류 밀도 회복 효과를 보여주었습니다.
Biohaven a présenté des données de sécurité étendues pour BHV-7000, leur nouveau médicament anti-crises, lors de la réunion annuelle 2024 de la Société américaine d'épilepsie. Les études de phase 1 sur des doses croissantes multiples ont démontré une excellente tolérance de la formulation à libération prolongée administrée une fois par jour, sans les effets indésirables typiques sur le système nerveux central associés à d'autres médicaments anti-crises.
Le médicament a montré une sécurité favorable à des doses allant jusqu'à 120 mg par jour pendant 15 jours, dépassant les doses actuellement évaluées dans des essais de phase 2/3 (jusqu'à 75 mg par jour). Les études ont révélé de faibles taux d'événements indésirables liés au SNC, sans somnolence ni troubles cognitifs signalés. Des données non cliniques supplémentaires ont montré l'efficacité de BHV-7000 dans la réduction de l'activité neuronale et la restauration de la densité de courant dans les variantes KCNQ2.
Biohaven hat auf dem Jahresmeeting 2024 der American Epilepsy Society erweiterte Sicherheitsdaten zu BHV-7000, ihrem neuartigen Antikonvulsivum, präsentiert. Die Phase-1-Studien zu mehrfach steigenden Dosen zeigten eine hervorragende Verträglichkeit der einmal täglich verabreichen erweiterten Freisetzungsformulierung, ohne die typischen zentralnervösen Nebenwirkungen, die mit anderen Antikonvulsiva verbunden sind.
Das Medikament zeigte eine günstige Sicherheit bis zu Dosen von 120 mg täglich über 15 Tage, was die in den laufenden Phase-2/3-Studien (bis zu 75 mg täglich) bewerteten Dosen übersteigt. Die Studien ergaben niedrige Raten von zentralnervösen Nebenwirkungen, ohne dass Benommenheit oder kognitive Störungen gemeldet wurden. Zusätzlich zeigten nicht klinische Daten die Wirksamkeit von BHV-7000 zur Reduzierung neuronaler Aktivität und zur Rettung der Stromdichte in KCNQ2-Varianten.
- Demonstrated excellent safety profile with no dose-limiting toxicities up to 120 mg daily
- No CNS-related adverse events commonly associated with anti-seizure medications
- Successfully progressing with 5 ongoing pivotal Phase 2/3 trials
- Showed positive results in rescuing current density in all tested pathogenic KCNQ2 variants
- None.
Insights
The Phase 1 safety data for BHV-7000 represents a significant development in epilepsy treatment. The excellent tolerability profile up to 120 mg daily without CNS-related adverse events typically associated with anti-seizure medications is particularly noteworthy. This differentiates BHV-7000 from existing treatments that often cause debilitating side effects like somnolence and cognitive impairments.
The nonclinical data showing rescue of current density in 50 loss-of-function KCNQ2 variants provides strong mechanistic validation. The selective Kv7.2/7.3 activation without GABAA effects suggests a potentially superior therapeutic window compared to existing options. The optical electrophysiology results demonstrating concentration-dependent dampening of neuronal excitability further support the compound's mechanism of action.
The innovative study design of the SHINE trial represents a significant advancement in clinical trial methodology for epilepsy. By utilizing a time-to-event endpoint rather than traditional fixed-duration designs, this approach minimizes patient exposure to placebo, addressing important safety concerns regarding SUDEP risk. The qualitative assessment of patient experiences through social media provides valuable real-world insights into treatment challenges, particularly highlighting the impact of adverse events on quality of life.
With 5 ongoing pivotal Phase 2/3 trials across multiple indications including focal epilepsy, idiopathic generalized epilepsy, bipolar mania and major depressive disorder, BHV-7000's development program is both ambitious and comprehensive. The extended-release formulation's favorable tolerability profile supports the potential for improved patient compliance through once-daily dosing.
- Reported expanded safety results from BHV-7000 Phase 1 multiple ascending dose studies, including the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies, demonstrating excellent tolerability at all doses evaluated without central nervous system (CNS) adverse effects typically associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances.
- Qualitative assessment of online social media platforms and forums provided a unique perspective of the unmet needs that people with epilepsy are vocalizing outside of the clinical setting, including the negative impact that ASM associated adverse events have on their quality of life.
- Additional nonclinical data presentations included characterization of BHV-7000 using optical electrophysiology as well as beneficial effects of BHV-7000 on pathogenic developmental epileptic encephalopathy-associated KCNQ2 variants
Jason Lerner, M.D., Medical Director and Epilepsy Clinical Lead at Biohaven, commented, "We are very excited to share the expanded safety results with the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies. We are encouraged to see BHV-7000 continue to demonstrate favorable safety and tolerability without dose-limiting toxicities or CNS adverse events commonly associated with other ASMs, such as somnolence. These results paired with previously demonstrated CNS target engagement in our Phase 1 EEG study and a nonclinical profile showing BHV-7000 is a selective Kv7.2/7.3 activator that dials out GABAA activation provide compelling rationale for why BHV-7000 offers a differentiated profile from other treatments currently available or in development."
Dr. Lerner continued, "The evidence to date with BHV-7000 represents a potential paradigm shift in the treatment of epilepsy as many patients continue to be burdened by adverse events and do not achieve adequate seizure control with existing medications. As we continue advancing 5 ongoing pivotal Phase 2/3 trials with BHV-7000, including studies in focal epilepsy and idiopathic generalized epilepsy, Biohaven remains committed to developing novel, efficacious, and well-tolerated therapies for people living with epilepsy."
In addition to 4 poster presentations at AES, Biohaven will be presenting 1 poster at the Partners Against Mortality (PAME) 2024 Conference in
American Epilepsy Society 2024 Annual Meeting Presentation Highlights:
Poster 1.486: Phase 1 Multiple Ascending Dose Studies Demonstrate Safety and Tolerability of BHV-7000, a Novel Kv7 Potassium Channel Activator
- BHV-7000 is a selective Kv7.2/7.3 activator that was safe and well-tolerated at dose levels up to 120 mg daily for 15 days with no dose-limiting toxicities; 120 mg exceeds the doses being evaluated in ongoing Phase 2 and 3 clinical studies of up to 75 mg daily in focal epilepsy, idiopathic generalized epilepsy, bipolar mania, and major depressive disorder.
- There were low rates of CNS-related adverse events and no somnolence or cognitive/mood disturbances reported.
- Most AEs were mild and resolved spontaneously; and there were no serious adverse events or severe adverse events.
- New data with the BHV-7000 once-daily extended-release formulation demonstrated excellent tolerability.
Poster 1.512: A Qualitative Assessment of the Epilepsy Patient Experience Through Social Media and Web-based Forums
- While seizure freedom remains the primary goal of epilepsy treatment, additional unmet needs of people living with epilepsy were assessed by investigating the patient experience directly through social media and online platforms where patients discuss epilepsy outside of a clinical setting.
- Patient perspectives and unmet needs were identified across 3 areas: antiseizure medication-associated adverse events, mental health, and stigma.
- The 4 most frequently discussed ASM associated adverse events included: sleepiness, insomnia, mood changes, and cognitive effects; comments from patients captured the negative impact these adverse events have on their quality of life.
- People with epilepsy also reported a range of challenges with mental health, and the stigma associated with epilepsy pressured patients to remain silent about their struggles.
Poster 1.534: Pharmacological Characterization of BHV-7000, a Novel and Selective Activator of Kv7 Channels, Using All-optical Electrophysiology
- The acute and chronic pharmacological effects of BHV-7000 on the excitability of primary rat cortical neurons were evaluated using the all-optical electrophysiology platform Optopatch (Quiver Biosciences), which measures neuronal activity with single-cell and single action potential resolution.
- Concentration-dependent dampening of neuronal excitability was observed, consistent with previous data with BHV-7000 in other experimental paradigms.
- Overall, BHV-7000 demonstrated potent in vitro effects to reduce neuronal activity impacting a diverse set of Optopatch functional features across the stimulus protocol, including spike timing and spike shape features in different stimulus periods, which indicates lower neuronal excitability near action potential threshold.
Poster 1.431: BHV-7000 Is a Potent M-current Activator with Efficacy on Multiple Epilepsy-associated KCNQ2 Variants
- This in vitro study assessed the effects of BHV-7000 on 50 loss-of-function KCNQ2 variants.
- BHV-7000 rescued current density in all tested pathogenic KCNQ2 variants.
- Current density was restored to wild-type (WT) levels with BHV-7000 for most variants.
- These findings support the potential therapeutic value of BHV-7000 in KCNQ2-related epilepsy associated with a wide range of pathogenic KCNQ2 variants.
Partners Against Mortality (PAME) 2024 Conference Highlights:
PAME Poster 41: A Modern Design for a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BHV-7000 in Idiopathic Generalized Epilepsy (IGE) With Generalized Tonic–Clonic Seizures (SHINE)
- Epilepsy studies have traditionally been double-blind, placebo-controlled, change-from-baseline endpoint studies; in these studies, subjects receiving placebo for a fixed treatment duration remain at risk for continued seizures, injury, and Sudden Unexpected Death in Epilepsy (SUDEP).
- SHINE (NCT06425159) is an innovative, ongoing registrational study in IGE with the selective Kv7 activator BHV-7000 with an efficient, patient-centric design utilizing an FDA-endorsed time to event endpoint that decreases time on placebo, potentially reducing the risk of exposure to additional seizures, injury, and SUDEP.
Full posters will be available on the Posters and Presentations page at: www.biohaven.com.
About BHV-7000
BHV-7000 is a novel and selective activator of Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and in regulating the hyperexcitable state, that is being developed for the treatment of epilepsy and mood disorders. BHV-7000 was rationally developed as a potent activator of heteromeric Kv7.2/7.3 potassium channels, the molecular substrate that underlies the M-current (IKM). BHV-7000 is highly differentiated from ezogabine (known as retigabine in
About Biohaven
Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and nonclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA (spinocerebellar ataxia); myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules and antibody drug conjugates for cancer. For more information, visit www.biohaven.com.
Forward-looking Statements
This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable
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FAQ
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