Blarcamesine(Anavex 2-73) is an investigational oral therapy being developed by Anavex Life Sciences to potentially modify the course of Alzheimer’s disease (AD), as opposed to treating specific disease symptoms
How Blarcamesine(Anavex 2-73) works?
Blarcamesine(Anavex 2-73) is a small molecule that activates the sigma-1 receptor, which is known to modulate cellular processes relevant to neurodegeneration. Specifically, Blarcamesine(Anavex 2-73) is thought to help restore cellular balance by targeting protein misfolding (when proteins fail to fold correctly, into a normal configuration, they do not work as intended), oxidative stress (which damages cells due oxygen molecules with free radicals, or unpaired electrons), mitochondrial dysfunction, inflammation, and cellular stress.
The sigma-1 receptor is a small transmembrane protein, a stress reducing and survival protein, mainly located on the endoplasmic reticulum membrane of cells. This receptor is also present on the surface of some nerve cells and multiple other central nervous system cell types and tissues. As sigma-1 receptors are present in various sites, different physiological and pathological processes may be influenced by treatment with Blarcamesine(Anavex 2-73).
The brain of a person with Alzheimer’s has fewer sigma-1 receptors than healthy people of the same age. Therefore the induction or activation of these receptors could improve the clinical symptoms of AD and protect against neurologic changes. Researchers believe that this activation may be achieved by the regulation of calcium and the reduction of oxidative stress.
Anavex 2-73 in clinical trials
A Phase 1 clinical trial assessing the safety and pharmacokinetics of Blarcamesine(Anavex 2-73) was successfully completed in healthy men in Germany. The maximum tolerated dose of the drug was determined to be 55 mg.
A Phase 2 study (NCT02244541) enrolled 32 participants with mild-to-moderate AD and consists of two parts: Part A, a five-week study to assess the safety, tolerability, and maximum tolerated dose of the drug, and part B, a 26-week open-label extension to establish the continued safety and tolerability of Blarcamesine(Anavex 2-73), exploring a dose-effect relationship.
The results showed a favorable safety profile for Blarcamesine(Anavex 2-73), important for further studies. The most common adverse effects were minor or grade 1, like dizziness and or headache, and most were resolved. Data on its pharmacokinetics, or how a drug is absorbed, distributed and expelled by the body, are still being evaluated.
But researches noted that “unexpected” therapeutic responses were seen in this Phase 2 trial, including improved alertness and mood, and better engagement with family and friends.
At the request of families, Anavex reported that a 104-week, open-label extension study (NCT02756858) was begun, enrolling participants with mild-to-moderate AD who took part in the previous trial. Its primary goal is evaluating treatment-related adverse events, but measures of life quality are also being assessed as secondary goals. The study is expected to finish in November 2018.