Anavex Life Sciences Announces Positive up to 4-Years Oral Blarcamesine Results from Phase IIb/III Open-Label Extension Trial in Early Alzheimer’s Disease

Insights

Biotechnology Analyst

Anavex's results from the ATTENTION-AD trial represent significantly positive long-term data for blarcamesine in Alzheimer's disease. The 4-year extension study demonstrated that patients receiving continuous treatment experienced statistically significant benefits in both cognition (ADAS-Cog13 with -3.83 point difference, p=0.0165) and daily function (ADCS-ADL with +4.30 point difference, p=0.0206) compared to delayed-start patients.

Particularly noteworthy is that the cognitive improvement exceeded 2 points on ADAS-Cog13, which is considered the threshold for clinical meaningfulness in Alzheimer's research. The delayed-start analysis design is specifically engineered to detect disease-modifying effects rather than merely symptomatic benefits, suggesting blarcamesine may actually alter disease progression.

The safety profile appears remarkably clean for an Alzheimer's treatment, with no treatment-related deaths and importantly, no ARIA (amyloid-related imaging abnormalities) such as brain swelling or microhemorrhages that have plagued other recent Alzheimer's approvals. The most common side effect (dizziness) proved manageable through adjusted titration schedules.

The oral administration route provides a massive competitive advantage over injectable antibody therapies, potentially expanding the addressable market significantly while reducing healthcare system burden. With 74 patients now receiving blarcamesine under compassionate use for up to 9 years with continued favorable safety, the drug demonstrates potential for the crucial long-term treatment paradigm needed for this chronic condition.

Clinical Neurologist

The ATTENTION-AD trial results demonstrate meaningful clinical differentiation in the crowded Alzheimer's treatment landscape. The 3.83-point ADAS-Cog13 difference between early and delayed treatment groups at 192 weeks is particularly significant - this exceeds the commonly accepted 2-point threshold for clinical meaningfulness and suggests early intervention produces superior outcomes.

The functional benefits shown through ADCS-ADL improvements are equally important, as maintaining daily living activities represents a critical goal in dementia care. The additional analysis showing even greater benefits in patients with minimal treatment interruption (-4.20 point ADAS-Cog13 improvement, p=0.0083 and +5.75 point ADCS-ADL improvement, p=0.0015) underscores the importance of continuous therapy.

The safety profile is remarkably benign compared to antibody approaches targeting beta-amyloid. The absence of ARIA (brain swelling/microhemorrhages) is a major advantage, as these complications require expensive monitoring protocols and restrict patient eligibility. The manageable nature of dizziness through extended titration (reduced from 25.2% to 9.6% incidence) demonstrates thoughtful protocol optimization.

Blarcamesine's mechanism targeting sigma-1 receptor activation represents a novel approach beyond the traditional amyloid/tau pathways. This potentially addresses multiple neurodegenerative processes simultaneously, which aligns with the growing recognition that Alzheimer's involves multiple pathological cascades requiring multi-modal intervention approaches.

ATTENTION-AD trial data through 192 weeks presented at AD/PD^TM 2025 Conference

Prespecified delayed-start analysis indicate disease-modifying effect of oral blarcamesine and importance of early and continued long-term treatment of chronic Alzheimer’s disease

Blarcamesine exhibited a favorable safety profile with no treatment-related deaths

NEW YORK, April 05, 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 amelioration on clinical decline showing continued clinically and meaningful benefit for early Alzheimer’s disease patients. ATTENTION-AD (ANAVEX^®2-73-AD-EP-004) trial result was presented at the AD/PD^TM 2025 Conference.

Continued blarcamesine treatment up to four (4) years demonstrated good comparative safety profile and no associated neuroimaging adverse events (no potentially fatal brain bleeding or brain swelling). 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, lasting up to 192 weeks, with an open-label extension (OLE) treatment duration of 96 weeks for participants in Canada 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 using the prespecified MMRM analysis method was significant, reflecting importance of early treatment initiation. Continued blarcamesine treatment—without interruption—is encouraged for more favorable clinical outcome that may indicate disease-modifying effect.

“The long-term clinical ATTENTION-AD study results are very meaningful, demonstrating that diagnosing and treating people earlier and consistently in the continuum of Alzheimer's disease may lead to greater clinical benefit,” 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. “Overall blarcamesine could mark a shift toward more effective and patient-friendly Alzheimer’s treatments addressing disparities in Alzheimer’s care within the global healthcare systems.”

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 up to Week 192 (LS mean difference -3.83, P = 0.0165), favoring the early start group. 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 difference between the treatment groups at Week 192 being larger than 2 points is considered a clinically meaningful improvement.³

Similarly, the delayed-start analysis for ADCS-ADL showed numerically favorable results for the early start group over the late start group up to Week 192 and reached statistical significance (LS mean difference +4.30, P = 0.0206).

An additional analysis, evaluating the therapeutic effect of continuous drug treatment versus treatment interruption between the end of DB trial and the beginning of the OLE trial versus a longer drug interruption, confirmed the beneficial blarcamesine treatment effect.

With few or no interrupted treatment days, blarcamesine treatment resulted in an improved treatment effect for both cognition, ADAS-Cog13 (LS mean difference -4.20, P = 0.0083) and function, ADCS-ADL (LS mean difference +5.75, P = 0.0015) at Week 192.

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. Furthermore, continued blarcamesine treatment—without interruption—is encouraged for even more favorable clinical outcome.

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 25.2% in the ANAVEX^®2-73-AD-004 trial to 9.6% in the ATTENTION-AD trial, demonstrating the manageable nature of the most frequent TEAE (dizziness).

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.

“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. The study 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 is a devastating chronic disease that affects tens of millions worldwide. We believe, the clinically meaningful study results combined with blarcamesine’s convenient once daily oral dosing supports long-term therapy and 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 The preceding double-blind trial (ANAVEX^®2-73-AD-004) began in Australia before the other regions (Europe and Canada), 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 = DB (double-blind) + OLE (open-label-extension) 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?

The trial showed significant benefits in cognitive function (ADAS-Cog13, -3.83 points) and daily living activities (ADCS-ADL, +4.30 points) through 192 weeks, particularly in early-treatment patients.

How safe is AVXL's blarcamesine based on the 4-year trial data?

Blarcamesine showed a favorable safety profile with no treatment-related deaths, no severe adverse events, and reduced dizziness side effects from 25.2% to 9.6% with adjusted titration.

What is the significance of the delayed-start analysis in AVXL's Alzheimer's trial?

The analysis indicated disease-modifying effects, showing greater benefits in patients who started treatment earlier compared to those who delayed treatment by one year.

How long have some patients been taking AVXL's blarcamesine treatment?

Some patients in the Compassionate Use Program have been taking oral blarcamesine for over 9 years, with 74 participants currently enrolled.

What advantages does AVXL's blarcamesine offer over other Alzheimer's treatments?

Blarcamesine offers convenient once-daily oral dosing, good safety profile with no brain bleeding or swelling, and demonstrated long-term effectiveness up to 4 years.