Results from Anavex Life Sciences Landmark Phase IIb/III Trial of Blarcamesine Presented at Alzheimer's Association Conference

Rhea-AI Summary

Anavex Life Sciences presented results from their Phase IIb/III trial of blarcamesine (ANAVEX®2-73) for early Alzheimer's disease at the 2024 Alzheimer's Association Conference. The oral, once-daily treatment significantly slowed clinical decline by 38.5% (50 mg) and 34.6% (30 mg) compared to placebo over 48 weeks. Key findings include:

1. Significant improvement in the primary cognitive endpoint (ADAS-Cog13)
2. Positive trends in functional measures (ADCS-ADL)
3. Significant results in the key secondary composite endpoint (CDR-SB)
4. Reduced brain atrophy in key regions
5. Good safety profile with no neuroimaging adverse events

Anavex plans to submit for EMA approval in Q4 2024. The company believes blarcamesine's oral administration and safety profile could provide broader access to early Alzheimer's patients.

Positive

• Blarcamesine significantly slowed clinical decline by 38.5% (50 mg) and 34.6% (30 mg) vs placebo at 48 weeks
• Primary cognitive endpoint ADAS-Cog13 showed significant improvement for both 50 mg and 30 mg doses
• Key secondary endpoint CDR-SB significantly improved vs placebo in both dose groups
• Blarcamesine significantly slowed brain atrophy in key regions
• Good comparative safety profile with no neuroimaging adverse events like ARIA
• EMA submission expected in Q4 2024

Negative

• Functional co-primary endpoint ADCS-ADL did not reach significance at Week 48
• Common treatment-emergent adverse event of dizziness occurred in 35.8% of participants during titration

Medical Research Analyst

The results from Anavex Life Sciences' Phase IIb/III trial of blarcamesine for early Alzheimer's disease are highly significant. The drug demonstrated a 38.5% and 34.6% slowing of clinical progression at 48 weeks for the 50 mg and 30 mg doses, respectively, on the primary cognitive endpoint ADAS-Cog13. This is a substantial improvement over existing treatments.

Importantly, blarcamesine showed benefits on both amyloid-beta levels and brain volume, addressing two key pathological hallmarks of Alzheimer's. The drug significantly slowed brain atrophy, with impressive reductions of 37.6% in whole brain atrophy, 63.5% in total grey matter atrophy and 25.1% in lateral ventricle expansion. These neuroimaging results provide strong evidence of the drug's neuroprotective effects.

The safety profile is particularly noteworthy. Unlike some other Alzheimer's treatments, blarcamesine did not cause Amyloid-related imaging abnormalities (ARIA) or neurological tissue damage. This favorable safety profile, combined with oral administration, could make blarcamesine more accessible and easier to manage for patients.

While the functional co-primary endpoint (ADCS-ADL) didn't reach significance, this may be due to the scale's reduced sensitivity in early Alzheimer's. The significant improvement in the CDR-SB secondary endpoint provides additional support for the drug's efficacy.

Pharmaceutical Industry Analyst

Anavex's blarcamesine represents a potentially game-changing development in the Alzheimer's treatment landscape. As an orally administered small molecule, it offers significant advantages over injectable antibody therapies in terms of convenience and potential cost-effectiveness.

The drug's differentiated mechanism of action, focusing on improving autophagy through SIGMAR1 activation, sets it apart from current amyloid-targeting therapies. This novel approach could position blarcamesine as a complementary treatment to existing options, potentially expanding the therapeutic arsenal against Alzheimer's.

The planned EMA submission in Q4 2024 suggests a relatively rapid path to potential commercialization. If approved, blarcamesine could capture a significant share of the Alzheimer's market, estimated to be worth $12.9 billion globally in 2023.

However, investors should note that the functional co-primary endpoint did not reach significance, which could potentially complicate the regulatory process. The company's ability to address this in their submission will be crucial.

Overall, these results position Anavex as a strong contender in the highly competitive Alzheimer's drug development space, with potential for significant market impact if blarcamesine gains approval.

Neurology Expert

The results of this Phase IIb/III trial for blarcamesine are indeed promising for the field of Alzheimer's disease treatment. The significant slowing of clinical decline, as measured by the ADAS-Cog13, is clinically meaningful and compares favorably to other treatments in development.

What's particularly intriguing is the drug's effect on brain atrophy. The 63.5% reduction in total grey matter atrophy is remarkable and suggests a potent neuroprotective effect. This could translate to meaningful preservation of cognitive function over time, which is the ultimate goal of Alzheimer's treatment.

The safety profile is another standout feature. The absence of ARIA is a significant advantage over amyloid-targeting antibodies, which have been plagued by this side effect. The main adverse event, dizziness, appears manageable through dose titration.

However, it's important to note the lack of significance in the ADCS-ADL functional measure. While this may indeed be due to the scale's reduced sensitivity in early Alzheimer's, it will be important to demonstrate functional benefits in future studies or real-world use.

If these results are replicated and lead to approval, blarcamesine could represent a major advance in Alzheimer's treatment, offering a convenient, safe and effective option for early-stage patients.

Oral, once daily blarcamesine significantly slowed clinical decline for early Alzheimer's disease patients with good comparative safety profile and no associated neuroimaging adverse events

Clinical benefit of blarcamesine consistently observed for both 30 mg and 50 mg treatment groups

Benefits of blarcamesine on both amyloid-beta and brain volume, two underlying pathological hallmarks of Alzheimer’s disease

EMA submission expected in Q4

NEW YORK, July 28, 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 comprehensive results from the Phase IIb/III study showing that blarcamesine (ANAVEX®2-73), once daily orally, significantly slowed clinical decline 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 Scientific Advisory Board at the 2024 Alzheimer's Association International Conference (AAIC).

Blarcamesine significantly slowed clinical progression by 38.5% and 34.6% at 48 weeks in 50 mg and 30 mg groups vs. placebo, respectively, on the prespecified primary cognitive endpoint ADAS-Cog13. As specified in the March 2024 FDA Guidance for Early AD, a sole cognitive measure can serve as the primary endpoint for early Alzheimer’s trials.¹ The protocol was designed with ADAS-Cog13 and ADCS-ADL as co-primary endpoints. The functional co-primary endpoint, ADCS-ADL, was trending positive but did not reach significance at Week 48. A possible explanation is that the ADCS-ADL scale is designed for AD with overt dementia and is less sensitive for early AD.² The prespecified key secondary composite endpoint CDR-SB, also recommended as an alternative primary endpoint for early AD in the new FDA guidance, is significant at both 30 mg and 50 mg at Week 48. The findings are supported by biomarkers from the A/T/N spectrum, including plasma Aβ42/40-ratio and reduction of brain atrophy. Blarcamesine significantly slowed brain atrophy in key regions of interest, including the whole brain by 37.6%, total grey matter by 63.5%, and lateral ventricles by 25.1%.

“These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration,” said Dr. Sabbagh. “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. The neuroimaging evaluation performed in the Phase IIb/III study demonstrated no neurological tissue damage such as hemorrhage or Amyloid-related imaging abnormalities (ARIA), as documented with other anti-amyloid targeted therapies. 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.”

Blarcamesine, a small molecule administered orally once daily, demonstrated numerically superior clinical efficacy 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 to the currently approved anti-beta amyloid monoclonal antibody drugs.

Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex commented: “Anavex's precision medicine approach, tailored to improving autophagy, a key clearance mechanism that removes protein aggregates and misfolded proteins across the Alzheimer's disease continuum and uniquely positions the Company to develop innovative solutions for patients and their families.” He continued: “People living with early Alzheimer's disease have the desire to maintain their sense of self for as long as possible. The study results provide the potential for people with more time to engage in meaningful activities. Full regulatory submission of blarcamesine in Europe (EMA) is expected in Q4 2024.”

For the primary endpoint ADAS-Cog13, blarcamesine is significantly better than placebo for both 50 mg (−2.149; P = 0.021) at 48 weeks and for 30 mg blarcamesine dosage groups (−1.934; P = 0.026) at 48 weeks. The key secondary endpoint CDR-SB was significantly improved vs. placebo in both 50 mg (−0.465; P = 0.045) and 30 mg (−0.502; P = 0.020) assigned dose groups. CGI-I was significantly improved in both 50 mg (−0.314; P = 0.008) and 30 mg (−0.248; P = 0.024) groups.

In the respective safety population, common treatment-emergent adverse events included dizziness, which was transient and mostly mild to moderate in severity, and occurred in 120 participants (35.8%) during titration and in 76 participants (25.2%) during maintenance with blarcamesine and 10 (6.0%) during titration and 9 (5.6%) during maintenance with placebo. These events are manageable by adjusting titration schedule to slower titration and nighttime dosing, as has been positively observed in the blarcamesine compassionate use program.

“Alzheimer’s disease is such a devastating disease that affects tens of millions worldwide. The findings from this and previous studies with blarcamesine in Alzheimer’s disease further strengthen our belief in the potential of addressing the complex pathology in Alzheimer’s disease through an upstream precision medicine compensatory process, autophagy through SIGMAR1 activation,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “We like to thank all the people involved in the study for their invaluable contributions and we look forward to continuing our journey to address the high unmet need for Alzheimer’s disease patients with a potential new convenient orally available treatment option for Alzheimer’s disease.”

The presentation is available on the Investors section of the Company’s website at www.anavex.com. Data from the blarcamesine Phase IIb/III ANAVEX®2-73-AD-004 trial to be published in an upcoming peer-reviewed journal.

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, Rett syndrome, schizophrenia 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 that restores 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 US Food and Drug Administration. Early Alzheimer’s Disease: Developing Drugs for Treatment Guidance for Industry. 2024.
² Potashman M, Pang M, Tahir M, Shahraz S, Dichter S, Perneczky R, et al. Psychometric properties of the Alzheimer’s Disease Cooperative Study – Activities of Daily Living for Mild Cognitive Impairment (ADCS-MCI-ADL) scale: a post hoc analysis of the ADCS ADC-008 trial. BMC Geriatr. 2023; 23(1).37.

FAQ

What were the main results of Anavex's Phase IIb/III trial for blarcamesine (AVXL) in Alzheimer's disease?

Anavex's Phase IIb/III trial showed that blarcamesine significantly slowed clinical decline in early Alzheimer's disease patients by 38.5% (50 mg) and 34.6% (30 mg) compared to placebo over 48 weeks. The primary cognitive endpoint ADAS-Cog13 and key secondary endpoint CDR-SB showed significant improvements for both doses.

What is the mechanism of action of blarcamesine (AVXL) for Alzheimer's disease?

Blarcamesine works through SIGMAR1 activation, which is believed to improve autophagy, a key clearance mechanism that removes protein aggregates and misfolded proteins across the Alzheimer's disease continuum. This represents a differentiated approach compared to current anti-amyloid therapies.

When does Anavex (AVXL) plan to submit blarcamesine for regulatory approval?

Anavex plans to submit blarcamesine for EMA (European Medicines Agency) approval in Q4 2024, based on the positive results from their Phase IIb/III trial in early Alzheimer's disease.

What advantages does blarcamesine (AVXL) offer compared to other Alzheimer's treatments?

Blarcamesine is an oral, once-daily treatment with a good safety profile, requiring no routine MRI monitoring. It showed no neuroimaging adverse events like ARIA, which are associated with some anti-amyloid therapies. These features could potentially provide broader access to early Alzheimer's patients.