Anavex Life Sciences Corp (AVXL)

[falconer66a]

No preclinical hints or evidence of problems.

... if [Rett and other] results don't come in as great as I expect they will, then I believe it would contradict all of the previous trials that I mentioned above.

Well said. My perspective, also.

After the thalidomide scandal (https://en.wikipedia.org/wiki/Thalidomide_scandal) effective clinical trials of proposed new drugs were appropriately mandated. Drugs attempting to treat or prevent cancers, central nervous system diseases, and others tend to interfere with, disrupt, or compromise any number of body processes. Rare is the powerful drug that confines its therapeutic outcomes to favorable resolutions of a single disease or process. Watch the TV ads for prescription drugs (those aren’t allowed in many countries). Behind all of the happy faces of treated patients and colorful scenery, the announcer reads off an expansive list of side effects, some of which include death.

And those are for FDA-approved drugs; drugs that have passed big Phase 3 double-blind clinical trials. Many other drugs failed in those trials, got struck from medical history — as should have happened with thalidomide. But proper clinical trials at the time were not mandated. No longer the case. Blarcamesine, to be approved as a treatment for Rett syndrome, Parkinson’s disease dementia, and Alzheimer’s must be proven both safe and efficacious in the three on-going clinical trials.

What are the chances for those outcomes? Most new drugs, especially those working chemically in the central nervous system, have a host of concomitant side effects; often very severe. When severity is great, beyond some arbitrary threshold, the proposed new drug gets cancelled by the FDA.

For blarcamesine (Anavex 2-73) the key is this. In neither murine (lab rodent) tests, nor in early human trials, at any dosages, have there ever been any severe side effects, “adverse events.” None.

As I’ve posted previously, before any proposed new drug goes to trial a host of standard preclinical tests must be done. Strong drugs (well, all drugs) can interfere with or disrupt any of these bodily processes. Here are some of the more prominent ones.

Genetic Disruptions: Chromosomes or nucleotide sequences (genetic codes) are chemically disrupted. Unwanted mutations are induced. Or in chromosomes gene expression is disrupted; all sorts of adverse genetic events occur.

Endocrine System Disruptions: Production or response to hormones is compromised. The chemistry of hormones is particularly delicate, open to all sorts of anomalies induced by new, extraneous bio-active chemicals (drugs).

Neurological Disruptions: Nerve or brain processes can be disrupted; especially by drugs that cross the blood/brain barrier and are active in neurons (such as blarcamesine).

Teratological Disruptions: Many drugs can disrupt the proper, normal development of embryos and infants (as did thalidomide). Birth defects must be absent.

There are any number of other classes of drug side effects, but these are the biggies. Simply, blarcamesine has shown none of these, in either animals or humans, at any realistic dosage levels.

In the, now, wide body of clinical research on blarcamesine, there is not a single case or incident of any disqualifying adverse event, either in humans or animals. Consequently, there is no reason to believe that any will appear in the three ongoing clinical trials in humans.

Blarcamesine’s unique mechanism of action (MOA) precludes its involvement in any of the disruptions. The molecule has no specific or even generalized endocrine activity. It does not in any way complicate or disrupt normal genetic processes. Nucleotide sequences of DNA (genes) are not changed or compromised. The drug does act inside nerve cells, but only propitiously. Lastly, no indications whatsoever that it interferes with embryonic or later body development (unlike thalidomide).

To presume that blarcamesine will produce disqualifying side effects in the present trials; when it has not in anything previous, is just that; presumptuous. Without evidence. Please tell. Why would those precluding outcomes not have appeared in either animals or humans yet, but all of a sudden will spontaneously reveal themselves in the Phase 3 trials? In all of the pre-clinical work, not a hint of anything bad. Just the opposite. The drug is safe, and produces very favorable therapeutic outcomes for the targeted CNS diseases.