Replies to post #248752 on Anavex Life Sciences Corp (AVXL)

[nidan7500]

RESEARCH IN CONTEXT

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167374/

Systematic review: The authors reviewed the literature using PubMed, clinicaltrials.gov, and relevant Alzheimer's disease (AD) meeting abstracts and presentations. This study is, to the best of our knowledge, the first reported genome-wide search for biomarkers associated with drug response in AD.
Interpretation of results: Our findings have led to the identification of two genomic variants and a clinical baseline to pre-specify patients most likely to respond to a SIGMAR1 therapy using blarcamesine.

Future directions: The findings from this analysis have led to an ongoing confirmatory, randomized, and placebo-controlled Phase 2b/3 study investigating blarcamesine in 450 subjects (NCT03790709).

SO WHAT YOU SAY?

My simple minded assessment is, they think they have identified which AD patients will/will not respond positively to A2-73 and how they will respond-measure/track/manage them . If I have that correct, it is a massively important accomplishment in many ways. The trial has been planned (NCT03790709), scheduled. Stay tuned. At least we feel a little better now. My problem is the timing is too far out. Now, all the increased emphasis on PDD and RSD strategy makes more sense. So, now the PDD trial just got a lot bigger for me. Now looks like Dr.M. had to replan b/c the HH AI data introduced big changes in study-trial planning. Still not happy w/long wait but understand why. Partnership of some kind seems more likely to me now that I see a different picture.

Some of the blocks are beginning to fit, just wish I had a time machine to fast forward.

[CogDiss 1188X]

Won’t have a chance to read the paper just yet, but will be looking for how far they went toward validation of causation over association in the relationships they identified. One assumes that would happen, them being scientists and all, but people misuse big data all the time.

Even if they stopped at association, that is not a short argument. It is still a positive step forward.

If anyone has read it and knows, would be interested in hearing your thoughts.

[georgejjl]

Results
Biomarkers with a significant impact on clinical outcomes were identified at week 57: mean plasma concentration of blarcamesine (slope MMSE:P < .041), genomic variants SIGMAR1 p.Gln2Pro (?MMSE:P < .039; ?ADCS-ADL:P < .063) and COMT p.Leu146fs (?MMSE:P < .039; ?ADCS-ADL:P < .063), and baseline MMSE score (slope MMSE:P < .015). Their combined impact on drug response was confirmed at week 148 with linear mixed effect models.

Mohammad Afshar, Coralie Williams, Federico Goodsaid, Frédéric Parmentier, Walter E. Kaufmann, and Harald Hampel contributed to the writing of the manuscript and review. All authors discussed the results, provided critical feedback, and approved the final version of the manuscript.

Harald Hampel is an employee of Eisai Inc. and serves as Senior Associate Editor for the Journal Alzheimer's & Dementia;

Harald Hampel is Vice President, Chief Medical Officer, Neurology Business Group at Eisai Inc.

https://twitter.com/harald_hampel?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor

Good luck and GOD bless,