New Phase IIb/III Clinical Data Demonstrates Over Three Years of Continuous Treatment with Oral Blarcamesine to Significantly Benefit Early Alzheimer’s Disease Patients
Anavex Life Sciences (NASDAQ: AVXL) announced positive results from its ATTENTION-AD trial, showing that over three years of continuous treatment with oral blarcamesine significantly reduced clinical decline in early Alzheimer's disease patients.
The trial demonstrated that patients who started treatment earlier showed greater stability of cognitive function compared to those who started later. The delayed-start analysis revealed significant differences in ADAS-Cog13 scores at Week 144 (LS mean difference -2.70, P = 0.0348) and Week 192 (LS mean difference -3.83, P = 0.0165).
The drug exhibited a favorable safety profile with mostly mild to moderate adverse events. The most common side effect, dizziness, was reduced from 25.2% to 9.6% after adjusting the titration period. Currently, 74 participants are receiving blarcamesine through the Compassionate Use Program, with some patients on treatment for over 9 years with no severe adverse events.
Anavex Life Sciences (NASDAQ: AVXL) ha annunciato risultati positivi dal suo trial ATTENTION-AD, mostrando che oltre tre anni di trattamento continuo con blarcamesine hanno ridotto significativamente il declino clinico nei pazienti con Alzheimer in fase precoce.
Il trial ha dimostrato che i pazienti che hanno iniziato il trattamento prima hanno mostrato una maggiore stabilità della funzione cognitiva rispetto a quelli che hanno iniziato successivamente. L'analisi dell'inizio ritardato ha rivelato differenze significative nei punteggi ADAS-Cog13 alla Settimana 144 (media LS differenza -2.70, P = 0.0348) e alla Settimana 192 (media LS differenza -3.83, P = 0.0165).
Il farmaco ha mostrato un profilo di sicurezza favorevole con eventi avversi per lo più lievi o moderati. L'effetto collaterale più comune, vertigini, è stato ridotto dal 25.2% al 9.6% dopo aver regolato il periodo di titolazione. Attualmente, 74 partecipanti stanno ricevendo blarcamesine attraverso il Programma di Uso Compassionevole, con alcuni pazienti in trattamento da oltre 9 anni senza eventi avversi gravi.
Anavex Life Sciences (NASDAQ: AVXL) anunció resultados positivos de su ensayo ATTENTION-AD, mostrando que más de tres años de tratamiento continuo con blarcamesina redujeron significativamente el deterioro clínico en pacientes con Alzheimer en etapa temprana.
El ensayo demostró que los pacientes que comenzaron el tratamiento antes mostraron una mayor estabilidad en la función cognitiva en comparación con aquellos que comenzaron más tarde. El análisis de inicio retrasado reveló diferencias significativas en las puntuaciones de ADAS-Cog13 en la Semana 144 (diferencia media LS -2.70, P = 0.0348) y en la Semana 192 (diferencia media LS -3.83, P = 0.0165).
El medicamento mostró un perfil de seguridad favorable con eventos adversos en su mayoría leves a moderados. El efecto secundario más común, mareos, se redujo del 25.2% al 9.6% después de ajustar el período de titulación. Actualmente, 74 participantes están recibiendo blarcamesina a través del Programa de Uso Compasivo, con algunos pacientes en tratamiento durante más de 9 años sin eventos adversos graves.
아나벡스 라이프 사이언스 (NASDAQ: AVXL)는 ATTENTION-AD 시험의 긍정적인 결과를 발표했으며, 경증 알츠하이머병 환자에게 경구용 블라르카메신을 3년 이상 지속적으로 치료한 결과 임상적 퇴보가 현저히 줄어들었다고 전했습니다.
이번 시험은 치료를 일찍 시작한 환자들이 나중에 시작한 환자들보다 인지 기능의 안정성이 더 높다는 것을 보여주었습니다. 지연 시작 분석에서는 Week 144(LS 평균 차이 -2.70, P = 0.0348) 및 Week 192(LS 평균 차이 -3.83, P = 0.0165)에서 ADAS-Cog13 점수에서 유의미한 차이를 나타냈습니다.
이 약물은 대부분 경미하거나 중간 정도의 부작용으로 긍정적인 안전성을 보였습니다. 가장 흔한 부작용인 어지러움증은 조정 기간을 변경한 후 25.2%에서 9.6%로 감소했습니다. 현재 74명의 참가자들이 연민적 사용 프로그램을 통해 블라르카메신을 받고 있으며, 일부 환자는 9년 이상 치료를 받고 있으나 심각한 부작용은 없습니다.
Anavex Life Sciences (NASDAQ: AVXL) a annoncé des résultats positifs de son essai ATTENTION-AD, montrant qu'un traitement continu de plus de trois ans avec blarcamesine a réduit de manière significative le déclin clinique chez les patients atteints de la maladie d'Alzheimer à un stade précoce.
L'essai a démontré que les patients ayant commencé leur traitement plus tôt présentaient une plus grande stabilité de la fonction cognitive par rapport à ceux ayant commencé plus tard. L'analyse du début retardé a révélé des différences significatives dans les scores ADAS-Cog13 à la semaine 144 (différence moyenne LS -2,70, P = 0,0348) et à la semaine 192 (différence moyenne LS -3,83, P = 0,0165).
Le médicament a présenté un profil de sécurité favorable, avec pour la plupart des événements indésirables légers à modérés. L'effet secondaire le plus courant, le vertige, a diminué de 25,2 % à 9,6 % après ajustement de la période de titration. Actuellement, 74 participants reçoivent de la blarcamesine dans le cadre du programme d'utilisation compassionnelle, certains patients étant sous traitement depuis plus de 9 ans sans événements indésirables graves.
Anavex Life Sciences (NASDAQ: AVXL) gab positive Ergebnisse aus der ATTENTION-AD-Studie bekannt, die zeigten, dass mehr als drei Jahre kontinuierliche Behandlung mit oraler blarcamesine den klinischen Rückgang bei Patienten mit frühen Alzheimer-Krankheit signifikant verringerten.
Die Studie zeigte, dass Patienten, die früher mit der Behandlung begannen, eine größere Stabilität der kognitiven Funktionen aufwiesen als diejenigen, die später begannen. Die verzögerte Startanalyse ergab signifikante Unterschiede in den ADAS-Cog13-Werten in Woche 144 (LS Mittelwertdifferenz -2,70, P = 0,0348) und Woche 192 (LS Mittelwertdifferenz -3,83, P = 0,0165).
Das Medikament wies ein günstiges Sicherheitsprofil auf, mit überwiegend milden bis moderaten unerwünschten Ereignissen. Der häufigste Nebenwirkung, Schwindel, wurde nach Anpassung der Titrationsperiode von 25,2 % auf 9,6 % reduziert. Derzeit erhalten 74 Teilnehmer über das Programm für compassionate use Blacamesine, wobei einige Patienten seit über 9 Jahren behandelt werden, ohne schwerwiegende unerwünschte Ereignisse.
- Significant reduction in clinical decline over three years of treatment
- Statistically significant cognitive improvements at Week 144 and 192
- Reduced side effect profile with adjusted titration (dizziness decreased from 25.2% to 9.6%)
- Long-term safety demonstrated with some patients on treatment for over 9 years
- Favorable safety profile with no treatment-related deaths
- Initial titration phase showed adverse events requiring adjustment of schedules
- Treatment requires extended titration period (increased from 2-3 weeks to 10 weeks)
Insights
The Phase IIb/III ATTENTION-AD trial data represents a significant milestone in Alzheimer's treatment development. The trial demonstrated that blarcamesine treatment for over 3 years showed meaningful cognitive benefits with a -2.70 point difference on ADAS-Cog13 at Week 144 and -3.83 point difference at Week 192, surpassing the clinically meaningful threshold of 2 points. The drug's ability to maintain cognitive function with early intervention is particularly noteworthy in the Alzheimer's therapeutic landscape.
The functional benefits measured by ADCS-ADL showing a +4.30 point difference at Week 192 further validate the drug's potential. The safety profile is remarkably clean, with manageable side effects and no treatment-related deaths - a important factor for long-term Alzheimer's treatments. The 74 patients in the Compassionate Use Program, some continuing for over 9 years, provide compelling long-term safety data.
From a market perspective, blarcamesine's oral administration and favorable safety profile position it uniquely in the competitive Alzheimer's treatment landscape. Unlike existing treatments requiring infusions or complex administration protocols, the once-daily oral dosing could significantly reduce healthcare system burden and improve patient compliance. The market cap of
The potential for early intervention and sustained benefits could translate to substantial market penetration, especially considering the drug's scalability and accessibility advantages. The comprehensive safety data and established manufacturing process reduce commercialization risks typically associated with novel Alzheimer's treatments.
The delayed-start analysis results are particularly compelling from a clinical perspective. The widening gap between early and late treatment groups strongly suggests disease-modifying potential - a holy grail in Alzheimer's treatment. The manageable side effect profile, particularly the reduced dizziness incidence from
The absence of neuroimaging adverse events and treatment-related mortality, combined with sustained efficacy over years, positions blarcamesine as a potentially transformative option for early Alzheimer's intervention. The fact that benefits continue to accrue through 4 years of treatment suggests a fundamental impact on disease progression rather than just symptomatic relief.
Topline ATTENTION-AD trial: Patients showed improved cognition and function over three years
Delayed-start analysis of treatment with oral blarcamesine was significant reflecting importance of early treatment initiation
Blarcamesine exhibited a favorable safety profile with no treatment-related deaths
NEW YORK, Jan. 13, 2025 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company focused on developing innovative treatments for Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) disorders, today announced that over three years of continuous treatment with blarcamesine (ANAVEX®2-73) demonstrated significantly reduced clinical decline showing continued clinically and meaningful benefit for early Alzheimer’s disease patients.
No new safety findings have been observed with continued blarcamesine treatment over three (3) years with good comparative safety profile and no associated neuroimaging adverse events. There were no deaths related to the study drug.
The ATTENTION-AD (ANAVEX®2-73-AD-EP-004) trial followed the 48-week ANAVEX®2-73-AD-004 double-blind (DB) clinical trial with an open-label extension (OLE) treatment duration of 96 weeks for participants in North America and Europe and up to 144 weeks for participants in Australia1 to evaluate the safety and tolerability of blarcamesine and long-term effects of blarcamesine on cognition and function in participants with early Alzheimer’s disease.2
Blarcamesine-treated patients continue to accrue benefit through up to 4 years, as measured by the clinical endpoints ADAS-Cog13 and ADCS-ADL. Delayed-start analysis of treatment with oral blarcamesine was significant reflecting importance of early treatment initiation.
“Long-term clinical ATTENTION-AD study results support the importance of continued long-term blarcamesine treatment,” said Prof. Dr. Timo Grimmer, MD, member of the Anavex Scientific Advisory Board and National Coordinating Investigator for the blarcamesine Phase IIb/III ANAVEX®2-73-AD-004 study. “Blarcamesine is easily scalable and might be a potential therapeutic solution for Alzheimer’s disease patients to potentially offer hope and relief and equitable and accessible for diverse populations and maintaining sustainability within the global healthcare systems.”
Topline Efficacy Data:
The delayed-start analysis was performed using the prespecified Mixed effect Model Repeat Measure (MMRM) model, to evaluate the effect of early treatment with blarcamesine on all data collected in both DB and OLE phases as the potential indication of disease-modifying characteristics of the treatment. Comparisons were made between ‘Continued blarcamesine’ and ‘Placebo to blarcamesine’ for ADAS-Cog13 and ADCS-ADL at the scheduled visits. ‘Continued blarcamesine’ is the early start group and ‘Placebo to blarcamesine’ is the late start group.
The delayed-start analysis for ADAS-Cog13 showed a significant difference between early start and late start treatment groups at Week 144 (LS mean difference -2.70, P = 0.0348), favoring the early start group. This observed treatment difference continued to increase up to Week 192 (LS mean difference -3.83, P = 0.0165). Together these results suggest that participants who initiated treatment with blarcamesine earlier in their disease progression showed greater stability of cognitive function compared to those who did not initiate blarcamesine until ~1 year later.
In addition, to place these findings in context, an ADAS-Cog13 score LS mean difference between the treatment groups at both Week 144 (OLE Week 96) and Week 192 (OLE Week 144) being larger than 2 points are considered clinically meaningful improvements.3
Similarly, the delayed-start analysis for ADCS-ADL showed numerically favorable results for the early start group over the late start group at Week 144 (LS mean difference +2.32, P = 0.125). The treatment difference continued to increase up to Week 192 and reached statistical significance (LS mean difference +4.30, P = 0.0206).
This suggests that earlier initiation of treatment with blarcamesine may have a significant positive impact on disease progression and may provide continued benefits to patients with early Alzheimer’s disease over the long-term.
Topline Safety Data:
Blarcamesine exhibited a favorable safety profile with the majority of adverse events (AEs) mild to moderate in severity (Grade 1 or 2), were predominantly linked to the initial titration phase, and could be managed with adjusted titration schedules. Importantly, no severe or life-threatening adverse events were attributed to blarcamesine. There were no deaths related to blarcamesine.
The ATTENTION-AD trial demonstrated the manageable nature of the most frequent treatment emergent adverse event (TEAE) of dizziness observed in the preceding ANAVEX®2-73-AD-004 trial, which was generally transient in duration (approx. 7-11 days) and mild or moderate in severity (Grade 1 or 2). The titration schedule was adjusted to a slightly longer titration period in the ATTENTION-AD trial, from previous 2-3 weeks to 10 weeks. A markedly lower frequency of the TEAE of dizziness in the respective maintenance phase was observed: from previously
Furthermore, no notable findings were observed over time in vital sign, clinical laboratory test, physical examination, electrocardiogram (ECG), and no pattern of serious adverse events (SAEs) were reported.
Compassionate Use:
Lastly, there are currently 74 participants receiving blarcamesine within the Compassionate Use Program, who continued treatment with blarcamesine subsequent completion of respective preceding open-label-extension studies from both ANAVEX®2-73-AD-EP-004 in early AD and from ANAVEX®2-73-003 in mild-to-moderate AD. Including the start of the respective preceding studies, some participants are on oral blarcamesine once daily for over 9 years. Importantly, no severe or life-threatening adverse events were attributed to blarcamesine.
“These results demonstrate that diagnosing and treating people earlier in the progression of Alzheimer's disease may lead to greater clinical benefit,” said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. “Additionally, the comprehensive data from the blarcamesine Alzheimer’s disease program represents a solid foundation for the subsequent strategy of our Phase III and IV development plan.”
“Alzheimer’s disease, like other chronic progressive diseases, requires a long-term therapeutic strategy. Blarcamesine mechanism of action with its convenient once daily oral dosing supports long-term therapy,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We remain excited about the scalable and convenient features of oral blarcamesine, which could be appealing because of its route of administration and good comparative safety profile. This could reduce crucial barriers within the currently complex healthcare ecosystem for Alzheimer's disease and potentially provide broader access to a diverse population with early Alzheimer's disease.”
ATTENTION-AD (ANAVEX®2-73-AD-EP-004) trial result details will be presented at the upcoming AD/PD™ 2025 Conference.
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
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1 The preceding double-blind trial (ANAVEX®2-73-AD-004) began in Australia before the other regions (Europe and North America), leaving insufficient time for the other regions to participate in the additional OLE extension beyond the initial 96 Weeks OLE period. The extension, requested by investigators in Australia, extended the initial 96-Week OLE period to 144 Weeks.
2 The scheduled visits were [OLE Week 0 = Combined Week 48], [OLE Week 48 = Combined Week 96], [OLE Week 96 = Combined Week 144] and [OLE Week 144 = Combined Week 192]; Combined = OLE (open-label-extension) + DB (double-blind) trials.
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
FAQ
What were the key results of AVXL's ATTENTION-AD trial for Alzheimer's treatment?
How safe is AVXL's blarcamesine based on the latest clinical data?
What is the significance of the delayed-start analysis in AVXL's Alzheimer's trial?
How did AVXL address the side effect of dizziness in the ATTENTION-AD trial?
