Anavex Life Sciences Corp (AVXL)

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Anavex 3-71 Succeeds Again, Now, as a Prophylactic!

To accurately discern the findings of the new journal article, telling the findings of Anavex 3-71 in the treatment of early-stage Alzheimer’s disease in transgenic rats (with inserted genetics mirroring those of humans with Alzheimer’s), I pulled up the publicly available article preview here:
https://www.sciencedirect.com/science/article/abs/pii/S0197458023002257?via%3Dihub

The paper appeared in Neurobiology of Aging, Volume 132, December 2023, Pages 220-232.

Here are key points in the paper.

Of course, there have been previous journal articles telling the findings of blarcamesine (Anavex 2-73) and Anavex 3-71 (AF710B) in the treatment of human CNS disorders genetically inserted into the genomes of murines (lab rodents). Each of those studies revealed positive efficacies (treatments), along with profound safety (lack of obviating or severe side effects).

But this study was new, investigating the ability of Anavex 3-71 to prevent or minimize the onset of Alzheimer’s-like symptoms. Simply, can Anavex 3-71 provide prophylactic, Alzheimer’s disease prevention outcomes? If so, this therapeutic modality would be greatly favorable to therapies that first require the presence of full-stage Alzheimer’s symptoms. Prophylaxis (prevention) as opposed to treatment (after the disease has caused CNS damage).

The authors stated: “We tested whether daily oral administration of AF710B (10 µg/kg) in 7-month-old, preplaque, McGill-R-Thy1-APP rats for 7 months, followed by a 4-week washout period, could prevent Alzheimer’s disease-like pathological hallmarks.”

At this point, one very important observation. The transgenic rats were dosed with 10 micrograms per kilogram of rat body weight. The largest lab rats weigh no more than 500 grams. If the study’s rats were large, they were getting 5 micrograms of Anavex 3-71 each day.

This is significant. Most of the other Anavex studies in murines have tested blarcamesine, Anavex’s leading new drug candidate for CNS diseases. But in those studies blarcamesine was dosed in milligram multiples, not tiny microgram amounts. Simply, Anavex 3-71 is far more active than blarcamesine. It requires doses in tiny micrograms. Blarcamesine requires doses in milligrams, generally an order of magnitude greater than Anavex 3-71. The authors of the study elected to test Anavex 3-71, instead of blarcamesine. They had reason to believe, then authenticated, that Anavex 3-71 would be the more favorable drug. I believe that, eventually, Anavex 3-71 will supplant blarcamesine and become Anavex’s lead pharmaceutical.

But, did the new drug actually work? Here’s what the authors claimed, “Long-term AF710B treatment prevented the cognitive impairment of McGill-R-Thy1-APP rats.”

Now, if this could likewise operate in humans, which would be the preferable clinical approach to Alzheimer’s? Presently: “We’ve done the clinical tests, and you, indeed, have Alzheimer’s. It’s now time for you to consider taking any of the existing new Alzheimer’s treatment drugs. They are expensive, and work only for a certain period of time, but they might give you a few years with symptoms where they are now.”

Or, “You are now entering the period of older age, after the age of 50, when Alzheimer’s first appears. We recommend that you now start taking a daily tablet of this new Anavex drug. Without any severe side effects, it will prevent or stop any Alzheimer’s symptoms.”

Questionable treatment after Alzheimer’s has set in? Or, prophylactic prevention, to keep the disease from ever occurring?

Of course, the Anavex critics will contend, once again, that mice (or rats) aren’t men; that murine studies are not useful in predicting new drug treatments in real humans. Of course, those with that perspective needn’t read or consider anything I or the company or the journal article have presented. But, in fact, the morphology (structure) and physiology (function) of murine nervous systems of murines parallel those of humans. This is not a matter of brain size or relative cognitive abilities. Those are different. But the distinct neurological structures and processes are the same.

Here’s a key finding. The drug produced a “reduction in the number of amyloid plaques in the hippocampus and the levels of Aß42 and Aß40 peptides in the cerebral cortex.”

No better biomarker for Alzheimer’s treatment efficacy. Amyloid plaques are almost universally regarded as the functional cause Alzheimer’s cognition-loss symptoms.

Additional positive outcomes, too: “AF710B treatment also reduced microglia and astrocyte recruitment toward CA1 hippocampal Aß-burdened neurons compared to vehicle-treated [non-dosed] McGill-R-Thy1-APP rats, also altering the inflammatory cytokines profile. Lastly, AF710B treatment rescued the conversion of brain-derived neurotrophic factor precursor to its mature and biologically active form.”

The authors made this bold claim, “Overall, these results suggest preventive and disease-modifying properties of the compound.”

Succinctly, Anavex 3-71, when used before Alzheimer’s sets in, in a prophylactic mode, actually works. It prevents the onset of Alzheimer’s symptoms. In this case, of course, only in transgenic lab rats. But, as any future trials in humans will prove, the same prophylaxis will occur. Eventually, Anavex 3-71 will be Anavex’s prime drug.