ANAVEX 2-73 is being studied as the first potential precision medicine biomarker-guided, targeted therapeutic in Alzheimer disease.
“Using a genetic biomarker in a study is like one step forward to a precision medicine approach in neuroscience.”
At the 2018 Alzheimer’s Association International Conference in Chicago, Illinois, Harald Hampel, MD, PhD, MA, MSc, professor at Sorbonne Universities, Department of Neurology, sat down with NeurologyLive to discuss the results of the entire genome DNA and RNA analysis of all study participants in the phase IIa study with ANAVEX 2-73, which resulted in the analysis of 33,311 genes and 860 pathways.
Anavex identified several genetic variants that impacted the response to ANAVEX 2-73, a selective sigma-1 receptor (SIGMAR1) agonist, which include SIGMAR1, ANAVEX 2-73’s target, and the Catechol-O-methyltransferase (COMT), a gene involved in memory function.
The results showed that patients with this SIGMAR1 gene variant or COMT show a less favorable response to benefit from treatment with ANAVEX 2-73 and excluding those with the variants—about 20% of the study group—resulted in improved scores on gold standard tests of cognition (MMSE) and activities of daily living (ADCS-ADL) (P <.05).
Including those with a milder disease (baseline MMSE ≥20) and excluding those with a SIGMAR1 variant resulted in an average improvement of +1.7 MMSE and +3.9 ADCS-ADL (P <.05) at week 57 compared to baseline, while excluding those with the COMT variant resulted in a score of improvement of +2 MMSE and +4.9 ADCS-ADL at week 57 compared to baseline.
The 57-week phase IIa study was conducted in 42 subjects with mild to moderate Alzheimer disease. This study, the first full genomic analysis of ANAVEX 2-73 in Alzheimer disease, represents a crucial step forward to precision medicine in order improve the potential of a drug getting to its intended target and reaching the right patients at the right time, Hampel added.
Hampel said the upcoming phase IIb/III study of ANAVEX 2-73, which will include 450 patients with early Alzheimer disease, includes genomic precision medicine biomarkers identified in the phase IIa study.