Anavex’s Phase 2b/3 Trial of Blarcamesine in Patients With Alzheimer’s Disease Shows Robust Clinical Efficacy & Slows Neurodegeneration

Anavex Life Sciences Corp. recently announced that a follow-on analysis of the landmark Phase 2b/3 study to treat early Alzheimer’s disease with the investigational drug blarcamesine (ANAVEX 2-73) did demonstrate a statistically significant slowing in cognitive decline associated with Alzheimer’s disease.

The clinical effect was complemented by two independent biomarkers: A significant reduction in pathological amyloid beta levels in plasma, as well as a significant slowing in the rate of pathological brain atrophy on MRI (Magnetic Resonance Imaging) scans.

The trial was a Multicenter (52 medical research centers/hospitals in 5 countries), randomized, double-blind, placebo-controlled, 48-week phase 2b/3 trial that enrolled 508 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia). Participants were randomized to receive blarcamesine (n = 338) or placebo (n = 170) oral capsules once daily for 48 weeks.

All prespecified clinical endpoints were analyzed using a mixed model for repeated measures (MMRM). The MMRM analysis method is the convention used for regulatory filings and discussions with regulatory authorities are in preparation.

The trial is successful in meeting the co-primary endpoints if the significance of each endpoint is P < 0.05, or if the significance of only one co-primary endpoint is P < 0.025. If only one primary endpoint is significant at an α level of 0.025, then the secondary endpoint will be evaluated at the same level of 0.025. The trial was successful, since the differences in the least-squares mean (LSM) change from baseline to 48 weeks between the blarcamesine and placebo groups were −1.783 [95% CI, −3.314 to −0.251]; (P = 0.0226) for ADAS-Cog13, and −0.456 [95% CI, −0.831 to −0.080]; (P = 0.0175) for CDR-SB in patients with early Alzheimer’s disease.

In addition, validated biomarkers of amyloid beta pathology, plasma Aβ42/40 ratio increased significantly (P = 0.048), demonstrating strong anti-amyloid effects of blarcamesine in Alzheimer’s disease patients, while MRI revealed significant reduction in brain volume loss, including whole brain (P = 0.0005), comparing treatment to placebo. In the respective safety population, common treatment-emergent adverse events included dizziness, which was transient and mostly mild to moderate in severity, and occurred in 120 participants (35.8%) during titration and in 76 participants (25.2%) during maintenance with blarcamesine and 10 (6.0%) during titration and 9 (5.6%) during maintenance with placebo.

“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, MD, Professor of Neurology and Chairman of the Scientific Advisory Board. “The advantage of blarcamesine (ANAVEX 2-73) 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.”

This is among the first drugs to prospectively demonstrate efficacy on biomarkers of neurodegeneration.

“These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration,” said Michael Weiner MD, Professor of Radiology and Biomedical Imaging, Medicine, Psychiatry, and Neurology at the University of California, San Francisco (UCSF) and Principal Investigator of the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

“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, PhD, President and Chief Executive Officer 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.”

Anavex Life Sciences Corp. is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex’s lead drug candidate, ANAVEX2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer’s disease, a Phase 2 proof-of-concept study in Parkinson’s disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX 2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s disease. ANAVEX 2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson’s Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX 2-73 for the treatment of Parkinson’s disease. ANAVEX 3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX 3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. For more information, visit www.anavex.com.