Categories Uncategorized

Anavex Reports Findings from Phase IIb/III Trial for Once Daily Oral Dementia Treatment

Anavex Life Sciences has announced results from its ANAVEX2-73-AD-004 Phase IIb/III trial, highlighting the efficacy and safety of blarcamesine (ANAVEX 2-73), a small-molecule treatment for early-stage Alzheimer’s disease (AD). This once daily oral dementia treatment was tested over 48 weeks in a multicenter, randomized, double-blind, placebo-controlled study involving 508 participants across 52 medical centers in five countries. The study focused on evaluating both cognitive and functional outcomes in participants with early-stage Alzheimer’s (Stage 3).

Key Findings from the Trial

Blarcamesine, which targets the activation of SIGMAR1 to restore cellular homeostasis, showed significant results in delaying clinical progression in Alzheimer’s patients. Participants were divided into three groups, receiving either a medium dose (30 mg), a high dose (50 mg) of blarcamesine, or a placebo. A total of 462 participants were randomized in the trial, and 338 (73.1%) completed the study.

The primary endpoints of the trial were cognitive and functional assessments using two recognized scales: the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Over the 48-week period, blarcamesine showed a significant improvement in both measures compared to the placebo group.

  1. ADAS-Cog13: Blarcamesine demonstrated a statistically significant reduction in cognitive decline. The difference in least-squares mean (LSM) from baseline to Week 48 between the blarcamesine and placebo groups was -2.027 (95% CI: -3.522 to -0.533), with a P value of 0.008.
  2. CDR-SB: A similar improvement was observed in the CDR-SB score, with a difference of -0.483 (95% CI: -0.853 to -0.114) and a P value of 0.010.

However, the trial did not achieve statistical significance in the ADCS-ADL (Alzheimer’s Disease Cooperative Study-Activities of Daily Living) functional outcome, with a P value of 0.357.

Biomarker and Safety Insights

In addition to cognitive and functional measurements, the trial also examined key biomarkers associated with Alzheimer’s disease. The Aβ42/40 plasma ratio, a marker of beta-amyloid burden, increased significantly in the blarcamesine group compared to placebo (P=0.048). Whole brain volume loss, a measure of neurodegeneration, was significantly reduced in patients receiving blarcamesine (P=0.002).

In terms of safety, the treatment demonstrated a favorable profile with no neuroimaging adverse events. The incidence of serious treatment-emergent adverse events (TEAEs) was comparable across the groups, with 16.7% of participants in the blarcamesine group and 10.1% in the placebo group experiencing such events. The most commonly reported adverse effect was transient dizziness, which was mostly mild to moderate in severity.

Potential Role of Blarcamesine in Alzheimer’s Treatment

The clinical outcomes from this study suggest that blarcamesine could offer a new approach to treating Alzheimer’s disease, focusing on upstream activation of SIGMAR1, a receptor linked to the regulation of cellular stress and autophagy. The findings show that treatment with blarcamesine significantly slowed cognitive decline by 36.3% in comparison to placebo, with individual reductions of 34.6% in the 30 mg group and 38.5% in the 50 mg group.

Further analysis of participants with a SIGMAR1 gene variant confirmed that the drug’s effect was enhanced in this subgroup, supporting the role of SIGMAR1 in modulating the pathophysiology of Alzheimer’s.

Future Implications for Alzheimer’s Treatment

Anavex has made a significant contribution to Alzheimer’s research with its Phase IIb/III trial of blarcamesine. This once daily oral dementia treatment may provide an alternative or complementary option to current anti-beta amyloid therapies. The company’s focus on a SIGMAR1 activation mechanism distinguishes it from many current therapies that predominantly target beta-amyloid pathology.

The findings from this study highlight the potential of blarcamesine as a novel, disease-modifying therapy for early-stage Alzheimer’s, pending further validation from extended trials. Anavex Life Sciences plans to continue its research to better understand the long-term impacts of blarcamesine, particularly through the open-label extension study ATTENTION-AD, which will further explore its effects in the coming year​.

This study positions Anavex Life Sciences at the forefront of Alzheimer’s research, contributing valuable new data on the potential to slow disease progression with an oral therapeutic approach. The results from this trial could have significant implications for how early Alzheimer’s is treated moving forward.

Leave a Reply

Your email address will not be published. Required fields are marked *