US biotech Anavex has been cleared to start a phase IIb/III trial of an Alzheimer’s drug that is designed to tackle three features of the disease – amyloid, tau and inflammation.
The company is hoping that by tackling all three characteristics linked to the pathology of Alzheimer’s it may be able to succeed where dozens of other trials – mainly looking at blocking the formation of amyloid deposits in the brain – have failed.
Anavex’ candidate is Anavex 2-73, a sigma-1 receptor (S1R) transmembrane protein activator that is thought to be involved in regulating homeostasis in cells, keeping them in a healthy, steady state by reducing factors such as oxidative stress, protein misfolding, mitochondrial dysfunction and inflammation – all of which are seen in the brains of Alzheimer’s patients.
In a phase IIa trial involving 32 Australian patients, the drug showed preliminary activity in improving attention levels and working memory, as well as improved psychomotor function. Media reports on the results focused on how some patients regained lost skills, such as the ability to play the piano, but the drug needs to be out through its paces in a much larger trial. Anavex is also conducting an extension phase for that initial study
That will get underway shortly, according to Anavex. It’s planning to recruit 450 patients with early Alzheimer’s at sites in Australia and North America into a 48-week protocol that will compare two doses of Anavex 2-37 to placebo.
The company has said it intends to select patients for inclusion into that study based on genomic biomarkers identified in its phase IIa study that chief executive Christopher Missling (pictured) says will enable “enriched clinical trial populations, more robust regulatory submissions and better characterised clinical trial designs.”
There’s little doubt that Anavex’ programme is high-risk, coming after the failure of dozens of amyloid-targeting drugs, various anti-inflammatory therapies including ibuprofen, and so far mixed results with tau protein-targeting therapies. But the biotech thinks that the broad activity of Anavex 2-73 and biomarker-driven clinical trials elevate its chances of success.
It is planning to use a similar process and trial design for a phase II study of Anavex 2-73 in Parkinson’s disease.