Anavex’s Blarcamesine Achieves Pre-specified Efficacy in Phase IIb/III Alzheimer’s Trial: Data Presented at CTAD Conference 2024
Anavex Life Sciences presented new data from their Phase IIb/III study of blarcamesine (ANAVEX®2-73) for early Alzheimer's disease at the CTAD Conference 2024. The oral, once-daily treatment demonstrated significant clinical efficacy through SIGMAR1 activation, slowing clinical progression by 36.3% in the primary endpoint ADAS-Cog13 over 48 weeks. In patients with SIGMAR1 wild type genes, progression slowed by 49.8%. The drug showed superior numerical clinical efficacy compared to approved therapies, with a good safety profile not requiring routine MRI monitoring. The company is proceeding with regulatory submission to EMA in Q4 2024.
Anavex Life Sciences ha presentato nuovi dati dal loro studio di fase IIb/III riguardante blarcamesine (ANAVEX®2-73) per l'Alzheimer precoce durante la Conferenza CTAD 2024. Il trattamento orale, somministrato una volta al giorno, ha dimostrato un'efficacia clinica significativa attraverso l'attivazione di SIGMAR1, rallentando la progressione clinica del 36,3% nel criterio primario ADAS-Cog13 nel corso di 48 settimane. Nei pazienti con geni di tipo selvatico SIGMAR1, la progressione è rallentata del 49,8%. Il farmaco ha mostrato un'efficacia clinica numericamente superiore rispetto alle terapie approvate, con un buon profilo di sicurezza che non richiede un monitoraggio RMN di routine. L'azienda sta procedendo con la presentazione regolatoria all'EMA nel quarto trimestre del 2024.
Anavex Life Sciences presentó nuevos datos de su estudio de fase IIb/III sobre blarcamesina (ANAVEX®2-73) para la enfermedad de Alzheimer temprano en la Conferencia CTAD 2024. El tratamiento oral, administrado una vez al día, demostró una eficacia clínica significativa a través de la activación de SIGMAR1, ralentizando la progresión clínica en un 36,3% en el criterio primario ADAS-Cog13 durante 48 semanas. En pacientes con genes tipo salvaje SIGMAR1, la progresión se ralentizó en un 49,8%. El fármaco mostró una eficacia clínica numérica superior en comparación con las terapias aprobadas, con un buen perfil de seguridad que no requiere monitoreo de rutina por RM. La empresa está avanzando con la presentación regulatoria a la EMA en el cuarto trimestre de 2024.
Anavex Life Sciences는 CTAD 컨퍼런스 2024에서 조기 알츠하이머병에 대한 blarcamesine (ANAVEX®2-73)의 2b/3상 연구 데이터의 새로운 결과를 발표했습니다. 하루 한 번 복용하는 이 경구 약물은 SIGMAR1 활성화를 통해 임상 진행을 48주 동안 주요 평가지표인 ADAS-Cog13에서 36.3% 감소시키는 중요한 임상 효능을 나타냈습니다. SIGMAR1 야생형 유전자를 가진 환자에서는 진행 속도가 49.8% 느려졌습니다. 이 약물은 승인된 치료법에 비해 우수한 수치적 임상 효능을 보였으며, 정기적인 MRI 모니터링이 필요 없는 좋은 안전성 프로파일을 가지고 있습니다. 이 회사는 2024년 4분기에 EMA에 규제 제출을 진행 중입니다.
Anavex Life Sciences a présenté de nouvelles données de son étude de phase IIb/III sur blarcamesine (ANAVEX®2-73) pour la maladie d'Alzheimer précoce lors de la Conférence CTAD 2024. Ce traitement oral, administré une fois par jour, a démontré une efficacité clinique significative grâce à l'activation de SIGMAR1, ralentissant la progression clinique de 36,3% sur le critère principal ADAS-Cog13 sur 48 semaines. Chez les patients ayant des gènes SIGMAR1 de type sauvage, la progression a été ralentie de 49,8%. Le médicament a montré une efficacité clinique numérique supérieure par rapport aux thérapies approuvées, avec un bon profil de sécurité ne nécessitant pas de surveillance IRM routinière. L'entreprise procède à une soumission réglementaire à l'EMA au quatrième trimestre de 2024.
Anavex Life Sciences hat auf der CTAD-Konferenz 2024 neue Daten aus ihrer Phase IIb/III-Studie zu blarcamesine (ANAVEX®2-73) bei frühem Alzheimer vorgestellt. Die orale, einmal täglich verabreichte Behandlung zeigte eine signifikante klinische Wirksamkeit durch die Aktivierung von SIGMAR1, die den klinischen Fortschritt über 48 Wochen um 36,3% beim primären Endpunkt ADAS-Cog13 verlangsamte. Bei Patienten mit SIGMAR1 Wildtyp-Genen verlangsamte sich der Fortschritt um 49,8%. Das Medikament zeigte eine numerisch überlegene klinische Wirksamkeit im Vergleich zu zugelassenen Therapien und wies ein gutes Sicherheitsprofil auf, das keine routinemäßige MRT-Überwachung erforderte. Das Unternehmen plant eine regulatorische Einreichung bei der EMA im vierten Quartal 2024.
- Clinical progression slowed by 36.3% in primary endpoint ADAS-Cog13
- Stronger efficacy (49.8%) in patients with SIGMAR1 wild type genes
- Superior numerical clinical efficacy compared to approved therapies
- Good safety profile without need for routine MRI monitoring
- Regulatory submission to EMA planned for Q4 2024
- None.
Insights
The Phase IIb/III trial results for blarcamesine show significant promise in treating early Alzheimer's disease. The drug demonstrated a
Key differentiators include:
- Oral administration (once daily) versus injectable competitors
- No requirement for routine MRI monitoring
- Novel mechanism targeting SIGMAR1 activation and autophagy
- Stronger efficacy in patients with specific genetic markers
This breakthrough positions AVXL strategically in the
The upcoming EMA submission represents a near-term catalyst that could significantly impact AVXL's market valuation. With a relatively modest market cap of
Data of Blarcamesine confirm upstream SIGMAR1 activation
Presented as Late Breaking Oral Communications at Clinical Trials on Alzheimer’s Disease (CTAD) Conference 2024
Oral, once daily blarcamesine meaningfully slowed clinical decline for early Alzheimer's disease patients with good comparative safety profile and no associated neuroimaging adverse events
NEW YORK, Oct. 31, 2024 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today presented new data from the Phase IIb/III study showing that blarcamesine (ANAVEX®2-73), once daily orally, demonstrates pre-specified clinical efficacy through upstream SIGMAR1 activation.
Clinical data confirmed the mechanism of action (MoA) by pre-specified SIGMAR1 gene analysis in people with early Alzheimer's disease (AD). The data were presented by Marwan Noel Sabbagh, MD, Professor of Neurology at Barrow Neurological Institute and Chairman of the Anavex Scientific Advisory Board at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, which is taking place October 29 - November 1, 2024, in Madrid, Spain.
SIGMAR1 is an integral membrane protein which activates an upstream compensatory process: Blarcamesine induces autophagy through SIGMAR1 activation resulting in restoring cellular homeostasis. In Alzheimer's disease patients, mutations (variants) of genes have generally been identified as disease risk factors. Likewise, impaired SIGMAR1 function (gene mutation, variants) leads to potential suboptimal function. Hence, patients who carry the non-mutated, common SIGMAR1 wild type (WT)1 gene, are expected to have stronger beneficial response to blarcamesine than patients with a SIGMAR1 mutation (variant), who nevertheless also benefited from treatment.2
This was confirmed in the Phase IIb/III study analysis: Over 48 weeks, blarcamesine significantly slowed clinical progression by
“These data are very exciting, particularly featuring blarcamesine’s novel upstream mechanism of action, enhancing autophagy through SIGMAR1 activation, a key clearance mechanism that removes protein aggregates and misfolded proteins across the Alzheimer's disease continuum,” said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. “The advantage of blarcamesine is that it is a small oral molecule that exerts clinical benefits on cognition and neurodegeneration and could be appealing because of its route of administration and good comparative safety profile. We are on track for regulatory submission of blarcamesine in Europe (EMA) in the current quarter 2024.”
Overall, blarcamesine, a small molecule administered orally once daily, demonstrated clinically meaningful improvement over 48 weeks with primary endpoint ADAS-Cog13 score being larger than 2 points.3 This suggests superior numerical clinical efficacy compared to approved therapies while also slowing neurodegeneration in early AD patients. Blarcamesine’s safety profile indicates not requiring routine MRI monitoring, and given its differentiated mechanism of action, could represent a novel treatment that could be complementary or an alternative to anti-beta amyloid monoclonal antibody drugs.
“Alzheimer’s disease is such a devastating disease that affects tens of millions worldwide. We believe, the clinically meaningful study results provide the potential for patients and their families to have a better and longer quality of life,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “We believe the scalable and convenient features of blarcamesine could reduce crucial barriers within the currently complex healthcare ecosystem for Alzheimer's disease and provide broader access to a diverse population with early Alzheimer's disease.”
The presentation is available on the Investors section of the Company’s website at www.anavex.com.
This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.
Forward-Looking Statements
Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.
For Further Information:
Anavex Life Sciences Corp.
Research & Business Development
Toll-free: 1-844-689-3939
Email: info@anavex.com
Investors:
Andrew J. Barwicki
Investor Relations
Tel: 516-662-9461
Email: andrew@barwicki.com
1 WT = homozygous dominant (TT)
2 Hampel H, Williams C, Etcheto A, et al. A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement (N Y). 2020; 6(1):e12013.
3 Muir RT, Hill MD, Black SE, Smith EE. Minimal clinically important difference in Alzheimer's disease: Rapid review. Alzheimers Dement. 2024;20(5):3352-3363. doi:10.1002/alz.13770
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