New Analysis Shows Anavex 2-73 Slows Cognitive Decline and Neurodegeneration in Patients with Early Alzheimer's Disease

Anavex Life Sciences, a clinical-stage biopharmaceutical company developing small molecule treatments for debilitating central nervous system diseases like Alzheimer's, Parkinson's, and Rett syndrome, recently announced that oral treatments of the investigational drug Anavex 2-73 (also known as blarcamesine) have been successful in significantly slowing the cognitive effects of early-stage Alzheimer's disease.

"These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration," Michael Weiner, MD, a University of California, San Francisco professor and principal investigator of the Alzheimer's Disease Neuroimaging Initiative, said in a press release.

Anavex 2-73: Clinical Trials for Cognitive Functioning

Anavex 2-73 is an orally available small molecule activator of the Sigma-1 receptor, a protein crucial to maintaining cellular homeostasis and critical brain functions like memory and the release of neurotransmitters. For neurodegenerative diseases like Alzheimer's and Parkinson's, activating these receptors provides neuroprotection by regulating cellular functions, preventing brain plaques, and reducing neuroinflammation and endoplasmic reticulum stress.

In a follow-up analysis of Anavex Life Sciences' Phase 2b/3 clinical trial assessing Anavex 2-73 as a treatment for Alzheimer's-related mild cognitive impairment, the data show that the drug's Sigma-1 activation is associated with significantly slower rates of brain shrinkage and significant reductions in amyloid beta (brain plaque) protein levels in the blood, two major biomarkers of Alzheimer's-related neurodegeneration. 

"There is hope that new therapies for Alzheimer's that target the disease beyond amyloid may slow progression of the disease for many people with the earliest forms of the disease," said Marwan Noel Sabbagh, MD, chairman of Anavex's scientific advisory board and a professor of neurology at the Barrow Neurological Institute. "The advantage of blarcamesine is that it is a small oral molecule that exerts clinical benefits on cognition and neurodegeneration and could be appealing because of its route of administration and excellent safety profile."

The Phase 2b/3 clinical trial, which took place over 48 weeks, enrolled 508 individuals from 60 to 85 years old with mild dementia or cognitive impairment associated with cognitive Alzheimer's disease. Each participant was randomly assigned to receive a once-daily oral dose of either Anavex 2-73 (338 patients) or a placebo (170 patients). 

This trial showed that patients treated with Anavex 2-73 were 84% more likely to have improved cognition based on an ADAS-Cog score drop of 0.50 points or better compared to the placebo. Additionally, these patients experienced a 45% slower cognitive decline compared to placebo takers and were 167% more likely to improve in daily functioning over the course of the study. The Anavex 2-73 treatment was also shown to significantly reduce cognitive and daily functioning based on the Clinical Dementia Rating Scale Sum of Boxes.

"People living with Alzheimer's disease desperately need new therapies and I am truly impressed with the outcome of this study, which demonstrated reversal of cognitive decline," Professor Stephen Macfarlane, head of clinical services at HammondCare and a principal investigator in Alzheimer's disease clinical trials, said in a press release surrounding the initial study.

Anavex 2-73 Extended Analysis

Following the recent analysis of the Phase 2b/3 results, patients taking Anavex 2-73 were found to have statistically significant score reductions on both the ADAS-Cog and Clinical Dementia Rating Scale Sum of Boxes tests compared to the placebo, indicating a slowed rate of cognitive decline. 

When analyzing the amyloid beta levels in Anavex 2-73 patients' blood, Anavex found increased ratios of AB42 and AB40, reflecting lower levels of brain plaque and a decreased risk of Alzheimer's. MRI results also reflected a significant reduction in brain shrinkage for patients taking Anavex 2-73 compared to the placebo.

Overall, the treatment is generally safe and well tolerated, with mild to moderate dizziness being the most widely reported side effect. Given its success, Anavex Life Sciences has extended its study of blarcamesine for early Alzheimer's treatment and continues to investigate its clinical benefits for other neurodegenerative diseases like Parkinson's and Rett syndrome.

"Alzheimer's disease is such a devastating disease that affects tens of millions worldwide, and Anavex's clinical development is a testament to our determination to follow the science," said Christopher U. Missling, Ph.D., president and CEO of Anavex. "We like to thank all the people involved in the study for their invaluable contributions and we look forward to advancing blarcamesine as a potential new, convenient, orally available treatment option for Alzheimer's disease."