Replies to post #343403 on Anavex Life Sciences Corp (AVXL)

[MayoMobile]

Good post. I'm keen for the CNS-wide preventative trial to initiate. I've mentioned historic FDA data for past preventative trials. They are rare, and usually target a specific pathology (i.e. Alzheimer's due to obesity). To my knowledge there has been only 1 other wide-reaching preventative trial testing a drug in the FDA registry.

[Investor2014]

Let me translate that back to reality.

One needs to be careful with these extrapolations from murine models. After all rat cognition and model of AD is not, with some exceptions I’m sure, not quite comparable to human cognition and AD.

Over 3 years mild AD human MMSE scores changes on average about 3 points for the worse and the variability is high. High enough that the typical short clinical trial of say 48 weeks isn’t enough to yield convincing stat sig results and clinically meaningful benefits without a very large number of patients enrolled eg. often N > 1000 and some subgroup fishing expeditions.

We had a subgroup of 2 patients in A2-73 P2a open label trial looking like reversion of AD. Most people don’t seem to understand or accept this is not equal to ‘we got this’.

Too early to get too excited about A3-71 for which we still haven’t seen even P1 results.

Next step for Anavex and AD is the A2-73 P2b/3 readout perhaps late this year.

Before that, very important to see positive results in AVATAR and EXCELLENCE. With that secured, then from there onwards slowly slowly catchy monkey - hopefully.

[Jonjones325]

Thanks. Much appreciated.

Missling is building a company that will be a CNS leader for decades to come.

With the powerful 3-71 on deck, why would we forge ahead with 2-73 if there was a hint of failure.

Why pile up the patents/IP in so many different indications? Because he knows 2-73 works and will lead for the first 10+ years while bringing up big brother so they can lead together for the next 10+ years.

Any CEO would shelve 2-73 if there were doubts, not pump more and more resources into it. They could have moved 3-71 up at the same time or at a slower pace in tandem, but went full steam ahead with 2-73. That tells me a lot.

Exciting times ahead. Snowball is getting bigger.

[georgejjl]

one rat month is comparable to three human years)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733029/

Importantly, these effects were maintained following a 5-week interruption of the treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232171/#B88-ijms-22-06359

Good luck and GOD bless,

[falconer66a]

As predicted, Anavex 3-71 next for Alzheimer’s

Based on these results, and ANAVEX®3-71 pre-clinical profile, the Company intends to advance ANAVEX®3-71 into a biomarker-driven clinical development dementia program for the treatment of FTD, schizophrenias and Alzheimer’s disease,....

https://www.anavex.com/post/anavex-life-sciences-reports-positive-results-from-phase-1-clinical-trial-of-anavex-3-71

Well, it appears that Anavex Life Sciences Corp, just as I did, sees Anavex 3-71 as a new, to-be-developed treatment for Alzheimer’s disease.

The results of the Phase I Anavex 3-71 trial, were announced:

ANAVEX®3-71 was well tolerated in all cohorts receiving ANAVEX®3-71 in single doses ranging from 5 mg to 200 mg daily with no serious adverse events (SAEs) and no significant lab abnormalities in any subject. In the study, ANAVEX®3-71 exhibited linear pharmacokinetics. Its pharmacokinetics was also dose proportional for doses up to 160 mg. Gender had no effect on the PK of the drug and food had no effect on the bioavailability of ANAVEX®3-71. The study also met the secondary objective of characterizing the effect of ANAVEX®3-71 on electrocardiogram (ECG) parameters. There were no clinically significant ECG parameters throughout the study. Participant QTcF measures were normal across all dose groups with no difference between ANAVEX®3-71 and Placebo.

All of this confirms and builds upon the previous murine, lab rodent data, from transgenic mice with genetically-induced human-type Alzheimer’s. As expected, this further confirms that sigma-1 receptor biology in murines is closely analogous to that in humans. What was seen in the rodents treated with Anavex 3-71 accurately predicted what was seen in humans. In this case, mice are (like) men.

Again, after blarcamesine for Alzheimer’s, it will be Anavex 3-71. Full clinical trials, of course, will have to be conducted, but there is not a microfragment of evidence, now in either rodents or humans that the drug will fail.

Of course, what needs yet to be determined are further, broader pleiotrophic outcomes, where sigma-1 receptor activation by the drug resolves not only Alzheimer’s, but a variety of other pathologies.