Anavex Life Sciences Announces ANAVEX®2-73 (Blarcamesine) Significantly Prevented Aβ (Abeta)-induced Cognitive Deficits with Confirmed Significant Biomarker-response in Animal Model of Alzheimer’s Disease

Rhea-AI Summary

Anavex Life Sciences Corp. (Nasdaq: AVXL) announced promising data indicating that ANAVEX^®2-73 can prevent cognitive decline associated with Alzheimer's disease. In preclinical studies, the drug showed significant protection against Aβ_25-35-induced cognitive impairments. The company plans to initiate a Phase 3 trial focusing on prevention in at-risk patients. Previously, clinical studies demonstrated cognitive improvements in Alzheimer's patients after treatment with ANAVEX^®2-73 over 57 weeks. These advancements highlight the drug's potential in addressing significant unmet needs in neurodegenerative therapies.

Positive

• ANAVEX^®2-73 showed effective prevention of cognitive decline in Alzheimer's model.
• Company plans Phase 3 trial targeting Alzheimer's prevention.
• Clinical data indicated cognitive improvements by +2.0 points on MMSE after 57 weeks.

Negative

• None.

Pre-Treatment with ANAVEX^®2-73 entirely prevented Abeta-induced cognitive decline

Anavex planning a Phase 3 prevention trial of ANAVEX^®2-73 including participants at risk for cognitive and functional decline related to Alzheimer's disease

NEW YORK, July 29, 2021 (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 and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) disorders, today reported new data that established ANAVEX^®2-73 to be a preventive treatment in the pharmacological model of Alzheimer's disease (AD). Pre-treatment with ANAVEX^®2-73, repeated once daily for one week before the Aβ (Abeta) challenge was protective in the Aβ_25-35 peptide model of Alzheimer’s disease in mice. ANAVEX^®2-73 significantly and dose-dependently prevented Aβ_25-35-induced biomarker-correlated cognitive impairments, which were assessed one week after the Aβ (Abeta) insult during which no further ANAVEX^®2-73 treatment took place.

ANAVEX^®2-73 activates the sigma-1 receptor (SIGMAR1). Data suggests that activation of SIGMAR1 results in the restoration of complete housekeeping function within the body and is pivotal to restoring neural cell homeostasis and promoting neuroplasticity.¹ SIGMAR1 also promotes autophagy and results in the degradation of amyloid-beta precursor protein (APP) thereby inhibiting Aβ production².

"We are excited about this data, which indicates the potential expansion for the ANAVEX^®2-73 platform to find an effective Alzheimer's prevention therapy, which might benefit the entire field," said Christopher U. Missling, PhD, President & Chief Executive Officer of Anavex. "In addition to finding treatment options for Alzheimer’s disease, we are also striving to find effective prevention therapies for this devastating disease, and this data might help advance this endeavor to address an area of high unmet medical need."

Data from this study will be submitted later this year for presentation at a scientific medical meeting.

Previously, a publication in Neuropharmacology noted that in a clinical study (ANAVEX2-73-002) of Alzheimer’s disease patients, 57 weeks of oral once daily ANAVEX^®2-73 treatment showed patients improved cognition scores by +2.0 points on MMSE, a 9% mean improvement from baseline to 57 weeks, corresponding to a calculated ADAS-Cog score change of -3.4 (improvement). In these same patients ANAVEX^®2-73 also improved ADCS-ADL, by +4.9 points, a 7% mean improvement from baseline to 57 weeks.³

An extension of the published study (ANAVEX2-73-003) demonstrated that for the same patients at week 70 MMSE scores improved by +3.0, a 14% improvement from baseline, corresponding to a calculated ADAS-Cog score change of -5.1 (improvement). In these same patients, ANAVEX^®2-73 also improved ADCS-ADL, by +6.0 points, an 8% mean improvement from baseline to 70 weeks. The mean MMSE and ADCS-ADL baseline scores for these patients in this study were 22.3 and 71.1, respectively.^4,5

This data seems to be consistent with the effect of ANAVEX^®2-73 on cognition assessed in the recently completed placebo-controlled Phase 2 study of 132 patients with Parkinson’s disease dementia (ANAVEX2-73-PDD-001) with once-daily administration of oral 30 mg ANAVEX^®2-73, 50 mg ANAVEX^®2-73 and placebo for 14 weeks. The observed statistically significant improvement of CDR system Episodic Memory of +42.22 between 50 mg ANAVEX^®2-73 and placebo was also dose-dependent (p = 0.003).⁶ CDR system Episodic Memory has been shown to be highly correlated (70%) with the ADAS-Cog score (r = 0.7).⁷ The calculated corresponding ADAS-Cog mean change from baseline score is -1.9 (improvement) for patients in the 50 mg dose group, an 8% mean improvement from baseline to 14 weeks. The difference between the ANAVEX^®2-73 group and the placebo group in the change from baseline at 14 weeks was a 4.0-point improvement of calculated corresponding ADAS-Cog score (p = 0.015).

The Company recently announced that it has exceeded its enrollment target for the ANAVEX^®2-73 (blarcamesine) double-blind, placebo-controlled late-stage Phase 2b/3 study (ANAVEX2-73-004) in Alzheimer’s disease.

Anavex Life Sciences’ product portfolio platform includes orally available small molecule drug lead candidate ANAVEX^®2-73 for the treatment of Alzheimer’s disease, Parkinson’s disease and Rett syndrome and ANAVEX^®3-71 for frontotemporal dementia.

About Alzheimer’s Disease

Alzheimer’s disease is a progressive degenerative brain disorder that gradually destroys a person's memory and ability to learn, reason, make judgments, communicate and carry out daily activities. An estimated 5.7 million Americans currently have Alzheimer's dementia. Alzheimer’s is the most common cause of dementia among older adults and is estimated to rank as the third leading cause of death for older people in the United States, just behind heart disease and cancer. In 2020, Alzheimer's and other dementias cost the nation approximately $305 billion. By 2050, these costs could rise as high as $1.1 trillion.⁸ There are currently over 50 million people living with dementia around the world, with numbers expected to increase to nearly 152 million by 2050.⁹ Almost 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3 seconds, and a significant increase in the caregiving burden placed on society and families.¹⁰

About Anavex Life Sciences Corp.

Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, pain and various types of cancer. Anavex’s lead drug candidate, ANAVEX^®2-73 (blarcamesine), successfully completed a Phase 2a clinical trial for Alzheimer’s disease and recently a Phase 2 proof-of-concept study in Parkinson’s disease dementia and a Phase 2 study in adult patients with Rett syndrome. ANAVEX^®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 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. ANAVEX^®3-71, which targets sigma-1 and 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 Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets
² Jaeger PA, Pickford F, Sun C-H, et al. Regulation of amyloid precursor protein processing by the Beclin 1 complex. PloS one. 2010;5(6):e11102.
³ Hampel H, Vergallo A, Caraci F, Cuello AC, Lemercier P, Vellas B, Giudici KV, Baldacci F, Hänisch B, Haberkamp M, Broich K, Nisticò R, Emanuele E, Llavero F, Zugaza JL, Lucía A, Giacobini E, Lista S; Alzheimer Precision Medicine Initiative. Future avenues for Alzheimer’s disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery. Neuropharmacology. 2021 Mar 1;185:108081. doi: 10.1016/j.neuropharm.2020.108081. Epub 2020 May 11. PMID: 32407924.
⁴ Hampel H. et al., 2018. Full genomic analysis of ANAVEX^®2-73 phase 2a Alzheimer’s disease study identifies biomarkers enabling targeted therapy and a precision medicine approach. Alzheimer’s & Dementia 14, P1519–P1520. https://doi.org/10.1016/j.jalz.2018.07.027.
⁵ Hampel H. et al. (2020). 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. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 6(1), e12013.
⁶ https://www.anavex.com/proof-of-concept-controlled-phase-2-clinical-trial-data-evaluating-anavex2-73-blarcamesine-in-parkinsons-disease-dementia-presented-at-ctad-2020-conference/.
⁷ Wesnes K. et al., Computerized cognition assessment during acetylcholinesterase inhibitor treatment in Alzheimer’s disease. Acta Neurol Scand 2010; 122:270–7.
⁸ https://www.nia.nih.gov/health/alzheimers; https://www.alz.org/alzheimers-dementia/facts-figures.
⁹ Alzheimer's Disease International. World Alzheimer Report 2019. https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf.
¹⁰ AARP. 2020 Report: Caregiving in the U.S. https://www.aarp.org/content/dam/aarp/ppi/2020/05/full-report-caregiving-in-the-united-states.doi.10.26419-2Fppi.00103.001.pdf.

FAQ

What is the significance of ANAVEX®2-73 in Alzheimer's disease treatment?

ANAVEX®2-73 has shown potential in preventing cognitive decline in Alzheimer's models, indicating its therapeutic promise.

When is the Phase 3 trial for ANAVEX®2-73 expected to start?

Anavex plans to initiate a Phase 3 prevention trial of ANAVEX®2-73 targeting participants at risk for Alzheimer's disease.

What improvements were observed in Alzheimer's patients using ANAVEX®2-73?

Patients in a clinical trial experienced a 9% mean improvement in cognition scores after 57 weeks of treatment with ANAVEX®2-73.

What are the clinical trial results related to ANAVEX®2-73?

Previous studies reported a +2.0 improvement on MMSE and a corresponding ADAS-Cog score change of -3.4 after treatment.