A Trial “Failure” Could Be A Great Success
Conduct of the announced clinical trial in Australia will yield incontrovertible results. It will be double-blind (no one knows who’s getting what), in three arms; approximately 150 Alzheimer’s patients taking a starch pill that looks and tastes exactly like the real ones (this, the control or placebo arm); then, two other arms of about 150 each, taking two different dosages of Anavex 2-73, the experimental arms. The trial is to run for 48 weeks.
In the earlier Australian clinical trial of Anavex 2-73, conducted only to assess dosing tolerability and safety (not actual efficacy against disease symptoms), only 32 patients were involved. Of those, six were apparent “super responders,” people for whom Alzheimer’s symptoms did significantly regress. It has been contended that those results cannot be relied upon, inasmuch as the clinical population was tiny; that such results could well have been mere chance, not a result of Anavex 2-73 per se.
Perhaps more significant, however, has been the request by trial participants in that study to continue to take the drug for an extended, continuing period after the formal trial ended. Readers will have to determine for themselves why those requests were a) made, and b) agreed to by Australian medical authorities.
Of course, Anavex has conducted precise genomic analyses on people in that first study, and have been able to discover statistical correlations between various genomic sequences (genes) and behavioral outcomes related to the Anavex 2-73 dosings in the study. With those data, participants in the new, much larger study are to include only those with Anavex-responsive genes. Of the 32 participants of the original study, six were “super responders,” about 18%.
This time, those exhibiting favorable treatment responses should be much higher, because they have been genomically pre-selected for favorable outcomes.
But, let’s imagine that the genomic selections were not accurate; that, in fact, genomic analysis was unable to accurately determine those Alzheimer’s patients most likely to respond well to Anavex 2-73 treatment. What if only 18% of the 300 people taking the drug get substantial relief, reversing debilitating symptoms so that a normal life could be once again lived? Would that be a clinical failure of Anavex 2-73? Let the reader discern.
But, here’s an alternative outcome that must be considered. There is a biochemical basis for it.
Let’s presume that, indeed, only 18% of the 300 people taking the drug in the upcoming Australian trial really gain, strong, discernable symptomatic relief. Good enough (or, not). The real issue is with the other 82% who did not show a strong, symptomatic turn around. How did the drug affect them? It clearly didn’t make them any better.
But what if, for the 48 weeks of the study, they all maintained the cognitive levels they had at the start of the trial? For 48 weeks, they didn’t get any better; just stayed the same? That would be a clinical failure of the drug?
What are the clinical implications if Anavex 2-73 turns out to be a drug that instead of reversing Alzheimer’s symptoms it merely stops their progression to ever-greater levels of severity?
What if the study determines that, at the least, symptoms will be maintained at the level of first administration of the drug? Would there be any market for a drug that might successfully prevent the progression of Alzheimer’s dementia at stages when it is first discovered, when patients could still live reasonably normal, non-institutionalized lives?
My father, tragically, succumbed to Alzheimer’s. He was an accomplished pubic accountant, with a well-developed practice. In his mid-60s, he and the family noticed a slowing of his mind. He could still think and relate with people; but at a slower pace. After several years of the continuance of his cognitive decline, he gave up his accounting practice, and in five or so years he mentally decayed to utter social debility. Like so many with the disease, he died in utter mental decay in an institution.
Such would not have been the case, were Anavex 2-73 available, and prescribed to him in his 60s, when his mental capacities first started to slow. Holding his cognition at that only slightly-reduced level would have allowed him to live an otherwise very normal life in his last decades.
So, I contend that if the Australian trial of Anavex 2-73 merely stops the progression of Alzheimer’s cognition decline, it will be a great success. That would be far better than the few approved Alzheimer’s drugs presently on the market. They don’t reverse or stop the progression of symptoms; they merely slow, for a time, their progression.
The biochemistry and cellular biology that would account for Anavex 2-73's ability to hold neuron functions at start-of-dosing baselines is reasonable. Simply, the molecule prevents the progression of neuron organelle dysfunction at an early stage. Where neurons are rather completely disrupted, where mitochondria and the associated endoplasmic reticula are no longer in proper chemical and mechanical alignment, Anavex 2-73 may not be able to restore the chemical collaborations of those two essential organelles.
But the presence of the drug, before things become profoundly misaligned, may well prevent progression to neuron dysfunction. Which national health service or medical insurance company wouldn’t support, endorse, and use such a drug for Alzheimer’s patients at their earliest diagnosis? A great success.
Reversal of Alzheimer’s symptoms would be great. Hope it will happen. But the mere suppression of their progression would be significant — better than anything on any pharmacy shelf. I see a very high chance for this.
AI
