New Data from Anavex Life Sciences: Blarcamesine Significantly Slows Cognitive Decline in Early Alzheimer’s Patients
Anavex Life Sciences, a biopharmaceutical company focused on developing novel therapeutics for neurodegenerative and neurodevelopmental disorders, has made significant strides with its lead drug candidate, ANAVEX®2-73 (blarcamesine). In recent clinical trials, blarcamesine has shown potential as a disease-modifying treatment for Alzheimer’s disease (AD). This article summarizes key findings from the ANAVEX2-73-AD-004 Phase IIb/III trial, which evaluated the efficacy and safety of blarcamesine in patients with early-stage AD.
Overview of the ANAVEX2-73-AD-004 Trial
The Phase IIb/III ANAVEX2-73-AD-004 trial was a 48-week, randomized, double-blind, placebo-controlled study conducted across 52 medical research centers in five countries. The trial included 508 participants diagnosed with early-stage Alzheimer’s disease (Stage 3). The primary goal was to evaluate the efficacy of blarcamesine in slowing cognitive and functional decline in these patients.
Participants were divided into three groups: 338 patients received either 30 mg or 50 mg of blarcamesine daily, while 170 patients were assigned to a placebo group. After completing the 48-week treatment period, participants were offered enrollment in the open-label extension study, ATTENTION-AD, which concluded in June 2024.
Primary and Secondary Outcomes
The co-primary outcomes of the study were changes in cognitive performance and functional abilities, as measured by the ADAS-Cog13 (Alzheimer’s Disease Assessment Scale-Cognitive Subscale) and the ADCS-ADL (Alzheimer’s Disease Cooperative Study-Activities of Daily Living) scales. Secondary outcomes included the CDR-SB (Clinical Dementia Rating-Sum of Boxes), plasma biomarkers related to Alzheimer’s disease (e.g., Aβ42/40 ratio), and changes in brain volume assessed via MRI.
The trial showed that blarcamesine had a significant impact on cognitive function. At 48 weeks, participants treated with blarcamesine demonstrated a notable improvement on the ADAS-Cog13 scale compared to those receiving a placebo, with a least-squares mean (LSM) difference of -2.027 (95% CI, -3.522 to -0.533; P=0.008). The CDR-SB score, which assesses functional decline, also improved significantly in the blarcamesine group compared to the placebo group, with an LSM difference of -0.483 (95% CI, -0.853 to -0.114; P=0.010).
However, the ADCS-ADL, which evaluates daily living activities, did not reach statistical significance, with a difference of 0.775 (95% CI, -0.874 to 2.423; P=0.357) between the blarcamesine and placebo groups at week 48.
Biomarker and Imaging Data
In addition to cognitive and functional improvements, blarcamesine also demonstrated positive effects on Alzheimer’s-related biomarkers and brain imaging data. Plasma levels of the Aβ42/40 ratio, a biomarker associated with Alzheimer’s pathology, showed a significant increase in patients receiving blarcamesine (P=0.048). Furthermore, MRI scans revealed that blarcamesine significantly reduced whole-brain volume loss compared to placebo (P=0.002), indicating a potential neuroprotective effect.
These findings suggest that blarcamesine may not only slow cognitive decline but could also positively impact the biological markers and structural changes associated with Alzheimer’s disease progression.
Safety Profile and Adverse Events
Blarcamesine was generally well tolerated by participants in the trial. The incidence of serious treatment-emergent adverse events (TEAEs) was slightly higher in the blarcamesine group (16.7%) compared to the placebo group (10.1%). Common side effects included dizziness, which was transient and generally mild to moderate in severity. Importantly, no neuroimaging-related adverse events were observed, further supporting the safety profile of blarcamesine as a potential treatment for early Alzheimer’s disease.
Potential Impact on Alzheimer’s Treatment
The results from the ANAVEX2-73-AD-004 trial provide a positive outlook for Anavex Life Sciences’ drug candidate, blarcamesine. By targeting the SIGMAR1 receptor, blarcamesine aims to restore cellular homeostasis and reduce the buildup of toxic proteins, which are hallmarks of Alzheimer’s disease. The trial data indicates that blarcamesine could significantly slow the progression of Alzheimer’s disease by improving cognitive function, reducing brain atrophy, and addressing key biomarkers.
While blarcamesine’s impact on daily functional abilities, as measured by ADCS-ADL, did not reach statistical significance, the positive results on cognitive and biological markers are encouraging. The drug’s favorable safety profile, combined with its neuroprotective properties, positions it as a candidate for further investigation and potential approval as a treatment for early-stage Alzheimer’s disease.
Anavex continues to advance its mission of developing innovative therapies for neurodegenerative diseases, with blarcamesine leading the way as a potential disease-modifying treatment for Alzheimer’s disease. The results from the Phase IIb/III ANAVEX2-73-AD-004 trial offer hope for patients and caregivers, as the drug demonstrates the ability to slow cognitive decline and improve brain health. Further studies and regulatory approval will be critical in determining whether blarcamesine can become a new standard of care for early Alzheimer’s disease.
