Anavex Life Sciences reports results for Alzheimer’s drug in Phase IIb/III trial

Anavex Life Sciences Corp., a clinical-stage biopharmaceutical company, has presented groundbreaking results from its Phase IIb/III trial of blarcamesine (Anavex 2-73) for treatment of early Alzheimer’s disease at the 2024 Alzheimer’s Association International Conference. The study demonstrates that the oral, once-daily medication significantly slowed clinical decline in patients with early Alzheimer’s disease.

The trial results, presented by Marwan Noel Sabbagh, M.D., professor of neurology and chairman of the scientific advisory board at Anavex, showed that blarcamesine reduced clinical progression after 48 weeks in patients who took 50-milligram doses (a 38.5% reduction) and those who took 30-milligram doses (a 34.6% reduction) when compared to those who took a placebo.

These findings were measured using the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, or ADAS-Cog13, a neuropsychological assessment used to measure the severity of cognitive symptoms related to dementia.

Anavex’sblarcamesine is a small molecule that targets autophagy enhancement through sigma-1 receptor activation, which is believed to play a crucial role in restoring cellular homeostasis. This mechanism of action differentiates blarcamesine from other Alzheimer’s treatments currently on the market.

Key Highlights From the Blarcamesine Phase IIb/III Clinical Trial

The clinical trial found that blarcamesine led to significant improvement in cognitive function for student participants, as measured on the ADAS-Cog13 scale. These improvements were found in those who took either 50-milligram or 30-milligram doses.

Participants also demonstrated positive trends in functional outcomes. While the functional co-primary endpoint — the Alzheimer’s Disease Cooperative Study-Activities of Daily Living, or ADCS-ADL, scale — did not reach statistical significance at 48 weeks, it showed a positive trend. Researchers suggest this may be due to the scale’s reduced sensitivity in early Alzheimer’s disease.

The trial’s findings are supported by biomarkers from the amyloid-tau-neurodegeneration spectrum, a biological framework that categorizes people based on AD biomarkers rather than clinical symptoms. These biomarkers included plasma Aβ42/40-ratio and reduction of brain atrophy. Blarcamesine significantly slowed brain atrophy in key regions of interest, including the whole brain (37.6%), total gray matter (63.5%), and lateral ventricles (25.1%).

The most common treatment-emergent adverse event was dizziness, which was generally mild to moderate and manageable through adjusted titration schedules and nighttime dosing.

Anavex’s Precision Medicine Approach Improves Autophagy

Juan Carlos Lopez-Talavera, M.D., Ph.D., head of research and development at Anavex, emphasized in the news release that the company has focused its efforts on boosting a brain function that clears out proteins associated with dementia.

“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, uniquely positions the company to develop innovative solutions for patients and their families,” he said.

The positive results from this trial have significant implications for AD treatment. Blarcamesine’s oral administration and favorable safety profile could potentially reduce barriers to treatment access and provide a more convenient option for patients with early Alzheimer’s.

Christopher U. Missling, Ph.D., president and chief executive officer of Anavex, expressed optimism about the drug’s potential.

“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,” he said.

Anavex To Seek Blarcamesine Approval From European Medicines Agency

Looking ahead, Anavex plans to submit a full regulatory submission for blarcamesine to the European Medicines Agency in the fourth quarter of 2024. The company also intends to publish the complete data from the Phase IIb/III clinical trial in a peer-reviewed journal.

It’s important to note that while these results are promising, blarcamesine is still an investigational drug. The company cautions that there is no guarantee that it will successfully complete clinical development or gain health authority approval.

Anavex continues to focus on developing novel therapeutics for neurodegenerative, neurodevelopmental, and neuropsychiatric disorders. In addition to Alzheimer’s, the company is exploring blarcamesine’s potential in other conditions such as Parkinson’s disease, Rett syndrome, and schizophrenia.

Note: This article discusses investigational uses of a product in development and does not intend to make conclusions about efficacy or safety. There is no guarantee that blarcamesine will successfully complete clinical development or gain health authority approval.