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Anavex Life Sciences recently reported follow-on analysis data from a Phase 2b/3 study of Anavex 2-73 for the treatment of Alzheimer’s disease. Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral changes.

Anavex is a clinical-stage biopharmaceutical company that is developing therapeutics for the treatment of a variety of neurodegenerative and neurodevelopmental disorders. Its multicenter, placebo-controlled, double-blind, randomized study of Anavex 2-73, also known as blarcamesine, was carried out at 52 medical research centers/hospitals in five countries. The study enrolled 508 patients with early symptomatic Alzheimer’s disease presenting with mild cognitive impairment or mild dementia.

Out of the total participants, 338 received Anavex 2-73 oral capsules and the remaining were given placebo once daily for 48 weeks. The study used a mixed model for repeated measures, after which the company analyzed all the prespecified clinical endpoints.

The trial met the co-primary endpoints as the differences in the least-squares mean change from baseline to 48 weeks between the Anavex 2-73 and placebo groups: negative 1.783 for ADAS-Cog13, and negative 0.456 for CDR-SB. Reductions in the rate of pathological brain atrophy on magnetic resonance imaging scans and the pathological amyloid beta levels in plasma were also observed.

How Alzheimer’s Disease Manifests and Impacts Cognitive Function

Clinically, Alzheimer’s disease manifests through a gradual progression of symptoms, typically affecting those over the age of 65. The pathological hallmarks include extracellular amyloid-beta plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. These aberrant protein accumulations disrupt neuronal communication, induce synaptic dysfunction and ultimately lead to neuronal death.

Early symptoms often involve subtle memory lapses and difficulties in word-finding or spatial orientation. As the disease advances, patients experience severe cognitive impairments, including disorientation, executive dysfunction, language disturbances, and impaired judgment. Behavioral and psychiatric symptoms such as agitation, depression and apathy are also common.

Diagnosis is primarily clinical, supported by neuroimaging techniques like MRI and PET scans, which reveal characteristic brain atrophy and amyloid deposition. Biomarkers in cerebrospinal fluid and blood, including decreased Aβ42 and elevated tau levels, further aid in diagnosis. Current therapeutic approaches are limited to symptomatic treatments, such as cholinesterase inhibitors and NMDA (N-methyl-D-aspartate) receptor antagonists, which provide modest cognitive benefits.

Research is ongoing to develop disease-modifying therapies targeting amyloid-beta and tau pathology, neuroinflammation, and synaptic preservation. Despite significant advancements in understanding Alzheimer’s pathogenesis, effective interventions to halt or reverse disease progression remain elusive.

Over 120,000 Alzheimer’s patients succumb to the disease annually in the U.S., and an estimated 6.7 million Americans age 65 and older are living with Alzheimer’s dementia today. Globally, the disease and other forms of dementia affects an estimated 55 million people. The total estimated worldwide cost of Alzheimer’s was $818 billion in 2015 (1.09% of global gross domestic product at that time). The annual global cost of dementia is now above $1.3 trillion and is expected to rise to $2.8 trillion by 2030.

Company Feedback and Outlook for the Future

“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 Missling, Ph.D., the president and CEO of Anavex.

Anavex 2-73 is the company’s lead drug candidate. It is designed to restore cellular homeostasis by targeting muscarinic and sigma-1 receptors. According to the company, blarcamesine has the potential to treat additional central nervous system disorders. In animal models, the drug demonstrated neuroprotective, antidepressant, anticonvulsant, and anti-amnesic properties.

“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,” Missling said.