In a follow-up analysis of a successful late-phase clinical trial for early Alzheimer’s disease treatment, an experimental therapy demonstrated both statistically significant slowing of Alzheimer’s-associated cognitive decline and biological evidence of reduced neurological degeneration.
The investigational drug blarcamesine, developed by New York-based Anavex Life Sciences and known as Anavex 2-73, was evaluated for clinical efficacy in a multicenter, randomized, placebo-controlled, Phase 2b/3 trial. The study enrolled 508 patients across 52 facilities in five countries taking a daily oral therapy over 48 weeks, with 338 patients receiving blarcamesine and 170 receiving a placebo. The follow-on analysis evaluated several primary and secondary endpoints, including clinical effects and critical biological markers of Alzheimer’s disease progression. The study reported results of the endpoints according to a mixed model for repeated measures, the conventional method used for regulatory filings and preparation.
“There is hope that new therapies for Alzheimer’s that target the disease beyond amyloid that may slow progression of the disease for many people with the earliest forms of the disease,” said Marwan Noel Sabbagh, M.D., professor of neurology and chairman of the Anavex Life Sciences scientific advisory board. “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.”
Anavex’s Blarcamesine Versus Placebo
The difference in clinical effects between patients taking blarcamesine and placebo was assessed with two widely used measures — the Alzheimer’s Disease Assessment Scale’s 13-question cognitive subscale and the sum of boxes of the Clinical Dementia Rating. The mean difference in the scores of these metrics between the blarcamesine and the placebo groups was among the study’s endpoints. These metrics indicated a successful trial.
Alzheimer’s disease is marked by progressive cognitive impairments and structural neurological degeneration. The cause of the deterioration in Alzheimer’s isn’t known, but is suspected to involve several pathways, including the pathological accumulation of amyloid beta protein deposits in the brain. Patients with Alzheimer’s disease have lower levels of sigma-1 receptors on their neurons than patients without Alzheimer’s. The sigma-1 receptor is believed to be important in regulating cellular processes in neurons and is one of the targets of action for blarcamesine.
In addition to the clinical findings, the study also showed a reduction of two independent biomarkers of neurological degeneration in those who received blarcamesine compared to those who received the placebo. After 48 weeks, patients in the blarcamesine group demonstrated a significant increase from baseline compared to the placebo group in the total plasma ratio of amyloid beta protein type 42 to type 40, an easily measured, predictive, blood-based biomarker that has been established for Alzheimer’s disease progression.
The strong anti-amyloid effect of blarcamesine was accompanied by a reduction in brain atrophy, another well-established marker in Alzheimer’s disease. When measured by an MRI, patients in the blarcamesine group had significantly less brain volume loss compared to the placebo group, including whole-brain measurements.
The safety profile of blarcamesine was also assessed in the study. Common treatment-emergent adverse events included dizziness, which was transient and mostly mild to moderate in severity. Dizziness occurred in 120 participants in the blarcamesine group and in 76 participants during the maintenance phase.
According to researchers and Anavex officials, the analysis showed that blarcamesine is among the first drugs to demonstrate efficacy on biomarkers of neurodegeneration, and the results support the progress of blarcamesine along the biopharmaceutical development life cycle toward approval as a treatment for early Alzheimer’s disease. “These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration,” said Michael Weiner, M.D., professor of radiology and biomedical imaging, medicine, psychiatry, and neurology at the University of California, San Francisco, and principal investigator with the Alzheimer’s Disease Neuroimaging Initiative.
“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.”
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Erik Jackson has been a senior editor at Health News Tribune for three years. Fluent in French and proficient in Spanish and Arabic, he focuses on diseases and conditions and the newest trends in medicine.
