Anavex Life Sciences Corp (AVXL)

[falconer66a]

Pretty deep, but phenomenally significant.

...could you please take the time to read (perhaps you have seen before) and give us the conclusion you reach what the article is saying.

insert-text-here

Well, thanks. Once again I turned to the paper, read it closely, with the goal of explaining what was investigated, and what was found. But, as anyone will quickly perceive when trying to read it, the article is extremely info-dense, with information not familiar to those not so competent in cellular biology, etc.

I first tried to condense and summarize the article for readers here. But after about the second page, of multiple big paragraphs with lots of terms that had to be explained, I gave up. Few would want to read much past my third paragraph. Scientifically arcane stuff; very hard to explain in a few paragraphs. So, let me tell what I found; what the paper discovered.

The study analyzed the “exome,” the genetic nucleotide sequences of participants, looking for portions of DNA (genes) that would correlate with therapeutic responses. Pretty advanced stuff, yielding very precise data; answering the question, “What genetics will allow blarcamesine to work, provide therapeutic results?”

I found this statement to be (for me at least) the most significant: “...the higher blarcamesine (ANAVEX2-73) mean concentration arm had improved therapeutic responses of 78% and 88% in adjusted MMSE and adjusted ADCS-ADL, respectively, relative to the low/medium arm at 148 weeks (P-values < .0008 and <.0001, respectively). In addition to time, APOE e4 status (P < .0001), and blarcamesine (ANAVEX2-73) mean concentration were significant predictors.”

Simply, for 78 to 88 percent of the humans being tested blarcamesine provided extremely significant therapeutic improvements.

First were the Mini-Mental State Examination (MMSE) numbers. The MMSE test runs like this: “Ask for the date. Then specifically ask for parts omitted (e.g., "Can you also tell me what season it is?"). One point for each correct answer. Ask in turn, "Can you tell me the name of this hospital (town, county, etc.)?" One point for each correct answer.” Simply, it’s a test of normal thinking, cognition skills—exactly what’s missing in those with Alzheimer’s.

The ADCS-ADL testing assesses the competence of patients with Alzheimer's Disease in basic and instrumental activities of daily living. The other deficiency factor in people suffering from Alzheimer’s.

Then, of course, were the “p-values.” Those indicate the chances that favorable results might have been by chance, not exactly by the drug being tested. P-values determine “statistical significance.” To be statistically valid (“significant”) there must be no chance greater than one in twenty that the results were random, not “significant” or actually caused by what it being tested. P values are in the range from 1.0 to 0.0, expressed in hundredths. A p-value of 0.05, the stat-sig cutoff (higher values indicate randomness, not direct effect) is a value of one-in-twenty.

Well, look at the study’s p-values: < .0008 and <.0001. Simply, blarcamesine works, profoundly in the majority of those with Alzheimer’s. But, as the genomic analyses show, not so well in 12 to 23% of those with the disease. They have genetic variants with reduced responses to blarcamesine.

What does all of this mean? Again, blarcamesine really does provide profound therapeutic outcomes for the majority of those with Alzheimer’s. Cognition was actually improved, not just maintained.

But, for a few, at the concentrations used in the study, blarcamesine had reduced or minimal therapeutic outcomes.

There is no doubt in my mind that when the final Alzheimer’s/blarcamesine study data appear, they will simply confirm these earlier data. With that, blarcamesine will get regulatory approval for sales and therapeutic use. In this study, the data are clear as day. Significantly improved scores of cognition and daily living, all with statistical significances entirely obviating any chance or otherwise anomalous causes. For most, blarcamesine WORKS for Alzheimer’s.

But what about those with unfavorable genetics, the 12 to 22 percent of study participants? For them, two additional studies will be needed. I perceive a really good chance that blarcamesine might be able to prevent the progression of Alzheimer’s in those people, if administered prophylactically, before and just at the appearance of symptoms; before the disease has set in and caused it’s cellular anomalies; or, those people may need much larger doses.

(Or, later, they will need Anavex 3-71, which very likely has differing underlying genetics.)