Replies to post #141280 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

I believe the gut microbiome analysis is exactly to understand how enzymes may affects metabolism therapeutic concentrations of A2-73 differently between patients.

[frrol]

Indirectly, perhaps. The metabolism of 2-73 (any drug) is important to is effectiveness. But this is what PK/PD data is for, and we have that. The hope is that the genomic impact is something relevant, but not likely metabolism. We already have the 2-73 serum concentration levels.

Directly, no. DPZ is a completely different molecule.

[OFP]

This is very interesting imho. Could it relate to A2-73?

“Recent studies demonstrate that the therapeutic response in AD is genotype-specific. Donepezil is metabolized via CYP-related enzymes, especially CYP2D6, CYP3A4, and CYP1A2. Approximately, 15%–20% of the AD population may exhibit an abnormal metabolism of AChEIs; about 50% of this population cluster would show an ultrarapid metabolism, requiring higher doses of AChEIs to reach a therapeutic threshold, whereas the other 50% of the cluster would exhibit a poor metabolism, displaying potential adverse events at low doses.

Essentially all were on the MTD and AVXL analyzed their data based on plasma levels not dose. Would expect that as a result genetic factors impacting metabolic rate would have minimal impact on their findings.