Anavex Life Sciences (Nasdaq: AVXL) has announced encouraging results from its ANAVEX2-73-AD-004 Phase IIB/III trial, evaluating the efficacy and safety of blarcamesine (ANAVEX 2-73) for the treatment of early Alzheimer’s disease (AD). The study, which involved 508 participants across 52 medical research centers in five countries, marks a significant milestone in the pursuit of a once daily oral Alzheimer’s treatment.
Blarcamesine, an orally available small-molecule developed by Anavex, works by enhancing autophagy through SIGMAR1 activation and restoration of cellular homeostasis. The 48-week, randomized, double-blind, placebo-controlled trial compared two dosage groups of blarcamesine (30 mg and 50 mg) against a placebo in patients with early AD (Stage 3).
The study’s co-primary outcomes were changes in ADAS-Cog13 and ADCS-ADL scores from baseline to 48 weeks. Secondary outcomes included the CDR-SB score and biomarkers from the A/T/N spectrum, such as plasma Aβ42/40-ratio and global brain volume changes measured by MRI.
Key findings from the trial include:
- Cognitive Function: Blarcamesine significantly slowed clinical progression by 36.3% at 48 weeks compared to placebo on the ADAS-Cog13 scale. The 30 mg and 50 mg groups showed improvements of 34.6% and 38.5%, respectively.
- Clinical Dementia Rating: The CDR-SB, a key secondary endpoint, showed significant improvement at Week 48 in the blarcamesine group relative to placebo.
- Biomarkers: Plasma Aβ42/40-ratio increased significantly in the blarcamesine group compared to placebo. Additionally, whole brain volume loss was significantly decreased in the treatment group.
- Safety Profile: The incidence of serious treatment-emergent adverse events (TEAEs) was 16.7% in the blarcamesine group compared to 10.1% in the placebo group. The most common TEAE was dizziness, which was generally transient and mild to moderate in severity.
- SIGMAR1 Gene Variant: A prespecified subgroup analysis confirmed the beneficial clinical effect of blarcamesine through upstream SIGMAR1 activation.
The trial results suggest that blarcamesine could represent a novel treatment option for early AD, potentially complementing or providing an alternative to anti-beta amyloid drugs. Importantly, the drug demonstrated a safety profile with no associated neuroimaging adverse events.
Anavex Life Sciences, the company behind blarcamesine, has a broader pipeline of drug candidates targeting various neurodegenerative, neurodevelopmental, and neuropsychiatric disorders. Their lead compound, ANAVEX®2-73 (blarcamesine), has shown potential not only in AD but also in Parkinson’s disease dementia and Rett syndrome.
The company’s approach focuses on restoring cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies have demonstrated the potential of ANAVEX®2-73 to halt and/or reverse the course of Alzheimer’s disease, as well as exhibit anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models.
Another noteworthy candidate in Anavex’s pipeline is ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors. This compound has shown disease-modifying activity against major hallmarks of Alzheimer’s disease in transgenic mice, including cognitive deficits, amyloid, and tau pathologies.
The success of blarcamesine in this Phase IIB/III trial represents a significant step forward for Anavex and potentially for the field of Alzheimer’s disease treatment. As an orally available drug with a novel mechanism of action, blarcamesine offers a unique approach to addressing the complex pathology of AD.
However, it’s important to note that while these results are encouraging, further research and regulatory approval processes will be necessary before blarcamesine can be considered for widespread clinical use. The medical community will be watching closely as Anavex continues to develop this and other compounds in its pipeline.
As the global burden of neurodegenerative diseases continues to grow, the work of companies like Anavex in developing novel therapeutics becomes increasingly crucial. The potential of blarcamesine to offer a disease-modifying treatment for early Alzheimer’s disease represents a beacon of hope for millions of patients and their families affected by this devastating condition.
