Replies to post #116262 on Anavex Life Sciences Corp (AVXL)

[falconer66a]

Fact Remains, Aricept Is Weak, Inadequate Alzheimer's Treatment

If Aricept were superior to Anavex 2-73, whatever it's actual molecular mechanism of action, why doesn't it exhibit such superiority in actual clinical use, in the multitude of Alzheimer's patients who presently take it (at least for the relatively short period it provides benefits)?

The actual chemical processes of both or either Aricept or Anavex 2-73 can be academically debated and contrasted. But for both Alzheimer's patients and AVXL shareholders, the only matter of importance is actual, practical clinical efficacy. Does this approved Alzheimer's drug provide safe, enduring stabilization or suppression of cognition deficits typically encountered in Alzheimer's patients?

Clearly, as the drug's label clearly indicates, Aricept provides only temporary, short-term symptomatic relief from Alzheimer's symptoms. After a certain (but variable) period of relief, symptoms will re-appear and the patient will irretrievably descend into ever more severe levels of dementia, culminating in a death that Aricept merely postponed for a period.

Wouldn't it be interesting to learn how many of the Australians in that clinical trial of Anavex 2-73, now so late in the game, have lost large degrees of cognition, or have even died from advanced Alzheimer's? How might they compare to any parallel group that has been dosed solely on Aricept for the same period?

Those data will probably never appear. But more valid data will, at the conclusion of the up-coming double-blind Phase 3 Anavex 2-73 Alzheimer's trial. Those with the slightest doubt about Anavex's superior treatment efficacy should refrain from taking any AVXL position until positive trial results appear, apparently sometime in late 2018 or later.

If the putative superiority of Aricept is to be the standard of comparison, Anavex has a very low bar to hurdle.

For some, they will have to safely wait and see. Others have already taken a well-considered initial Anavex position. To each, his own.

[jimmy667]

Donepezil is an S1 agonist with a higher binding affinity than 2-73 and apparently stronger effects according to some biomarkers as proposed in a recent paper (cited by our company itself).

This statement means very little in the 'real multi-dimensional complicated world of natural bio-mechanisms.' Clearly, A2-73 has been described as an activator of S1 in a very specific way, causing S1 to take positive steps to correct a cellular level problem. (The analogy was alerting a firetruck. S1 as a firetruck where A2-73 is the call to action.) If some other noise is louder and more easily heard by the fire brigade does not mean that sound will call to action mobilization of the fire brigade.

It is the effect of the drug or interaction of the drug with the S1 receptor that matter. If one were to yell in anger at his wife and children
their ears would hear that sound more surely and clearly than sweet words barely whispered. When the whispered words were heard they would more likely have a positive effect. The negative side effects of yelling angry words even louder at one's family to be heard would likely increase with the volume. But increasing the volume of the sweet loving words to overcome the loader sound (higher binding affinity) of the TV would likely not have negative effects due to the increased volume.

The importance of Donepezil higher binding affinity might be when it is co-administered with A2-73. Theoretically this could inhibit A2-73 action by dominating the receptor site. Apparently what has been found is if the dose of Donepezil is reduced to a specific dose or ratio then the two drugs work together. Anavex now has a patent for the A2-73/Donepezil combination drug that will be formally issued and day now.

The efficacy of the drug will be shown by clinical trials and the measurement of the affinity to S1 is not relevant especially in a drug with the safety profile of A2-73.

Arguments that other drugs have a higher affinity for S1 so maybe better
than A2-73 is a Red Herring and is oversimplified failed logic. That would make as much sense as a counselor telling someone to yell as his family in anger to promote a harmonious family life. Or for Doctors to RX cocaine or meth-amphetamine for cognitive impairment. (also drugs with a relatively high affinity to S1)

Remember what Dr George Perry MD renowned ALZ researcher and Editor of the Journal of the Alzheimer's Assoc. had to say about A2-73. Measure that against the failed and flimsy logic of a Frroll or OFP.