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Maybe one day we will be able to celebrate with a nice Battenberg Cake.
Won't have time to listen live to the Conf Call, but please do report here on any amazing revelations in the Q&A with all the analysts.
End 2024 will be another good time to buy $AVXL..but I don't smell any smoking shorts as has been promised here.
Oh and:
Well that's good to know:
Will there be news this morning causing shorts to cover?
Good move! Me too about 12 years ago.
Early intervention, whether safe drugs that actually work or life-style changes, have got to be better sooner rather than later or too late.
Interesting to see money flowing, at least today, into high risk/return plays like $SAVA and $AVXL.
I doubt we are seeing short covering, certainly given the $SAVA move. It perhaps does make sense that for now a better risk/return has to be found in less conventional investments and thus money are flowing into e.g. some select biotech plays. It will likely be short lived unless and until Anavex actually files and have an MAA validated by the EMA CHMP.
I will likely buy back, but not just now!
Just watch and learn whippersnapper.
U.S. Job figures out and stock markets tanking, not much $AVXL dry powder from Georgejjl naïve interest rate silliness.
As Cresent pointed out economic context is important, not just figures standalone. Very similar to how one can't just see $AVXL as a WGT investment based on context less great P-values etc.
Might see $AVXL back in the $5's today.
Boi statistics and Georgejll predictions should be view with critical thinking and great skepticism, IMO!
Be investors, as someone rightly says.
Yes and besides the only thing that will really move $AVXL in a positive sustained direction is a drug approval in some indication. Will that happen any time soon, like perhaps early 2026 by EMA in AD with A2-73? Hmmm...the answer is, maybe, definitely maybe...and I'll leave out the percentage chance this time.
And Georgejll, hold the clowns until at least after you have had some autophagy sleep.
You are all seeing the limitations of Large Language Models (LLM), which is exactly that and understands absolutely nothing about the contents and its context. LLMs are great language tools, but only for those who see them as such and can identify and correct for knowledge domain issues.
Try telling an LLM its answers is wrong and give a hint as to what and see it oblige with perfectly good semantics, but no critical thinking abilities based on actual domain knowledge.
Read and think about this in context of the trial design and its Intention-To-Treat population.
“Lower n is less ideal but it makes it harder to show a low p value so does in a sense show consistent efficacy strength in that regard.”
To help with the exercise, read my post about ITT vs Complete analysis.
You really need to carefully examine the table again, and slowly, including doing a maths check between a couple rows.
Please report back when you have completed the exercise and come to a different conclusion than your previous one.
I believe the question was rhetorical.
There are many other conceivable and inconceivable issues that did not occur. Like with the ARIA example, none of them will influence the factual low n completing the trial and that it appears all results are based on Completer analysis instead of an mITT population.
There no references to ITT population in the Anavex AAIC slides. There has been in other Anavex trial results slide decks as there should be in any such presentation of clinical trial results - it has got to be what the premise of the result analysis were!
It appears quite clear reviewing the results in light of the high and early dropout rate that the company is presenting Completer analysis only!
If everyone just waited for Missling and Co. to make something happen, then there wouldn’t be much other than perhaps some TA going on this MB 😉
lol!
“Fair point but what evidence would there be someone who dropped out at week 12 due to tolerability was going to fail to beat placebo at 48 weeks”
Complete misunderstood comment. It’s the other way around as randomised controlled clinical trials exist to prove a drug is safe and works!
Not guessing that dropouts might have worked better than placebo.
Biotech investing is not for everyone!
I’m saying that I see you don’t understand the concepts of Completers vs. Intention Treat trial in a clinical trial population and therefore not either the statistics of accounting for dropouts and missing data.
Of course there comes a point when dropouts and missing data gets too high, and here in a relatively small trial, to usefully account for it and still having a chance of stat sig results. That is where the Anavex P2b/3 must be, as otherwise the company would have written ITT on all their results.
Lol! someone should be having autophagy sleep, while I'm having my breakfast of fried herring in chocolate sauce.
No SAEs were reported, but there are clearly tolerability issues causing over 30% discontinuations.
That the company then proceeds with Completer analysis only is a big if for the veracity of the results presented.
The signals look good, but doubt these trial results will lead to full approval by EMA as the company apparently has been advised to apply for. I don’t know on what basis exactly the company has stated so.
Nor do I know why a potential MAA filing is delayed according to the company to Q4. It could be to include OLE analysis hoping that gives further support, but here I’m sceptical too that data with no controls can help improve Completer only analysis from a proportion of those same survivor bias patients likely to dwindle further during 96 weeks OLE.
Had the same results been from ITT population analysis, I would think approval more likely. In my view this will more likely mean that another larger trial designed to navigate the titration issue will be required.
I am revising my chance of approval in AD from current trials to less than 20% on the outside chance that a conditional approval could be granted with label restrictions, if possible, that lowers TEAEs and optimises response.
Yes Georgejjl ought to have realised that by now.
Read the second half of the paragraph you quoted again.
As you might know amyloid plague is considered toxic to neurons. By halting to some extent the formation of new amyloid plaques in the dose arm vs. placebo it would reduced brain atrophy caused by dying neurons.
I can only agree with that and is a pretty significant flaw in every trial so far!
Yes of course but only if your powder is still dry!
It does looks like $AVXL will close today at or near the low on less that 1m shares.
I guess my first paragraph could have been better formulated.
Nick Fox making the case mAbs causes quite dramatic brain volume loss by very effectively removing built up amyloid plaque, does make sense to me. We only see a very small reduction in atrophy with A2-73 vs. placebo, although still atrophy is occuring. That small reduction in atrophy, in part at least, could well be an expression for not much already built up amyloid plaque (6% - 8% of overall brain volume - per the article) being removed by some unquantified increase in autophagy. Combine this with some level of halt in new amyloid plaque accumulating and you may see a positive difference in atrophy vs. placebo with what seems an impressive P value.
An important point though remains that the trial ran into the titration paradox, which may cause regulators to view the trial results as unreliable. This especially when, as it seems, the results presented apply to Completer analysis - not ITT with statistics accounting for dropouts. Even so we see the standard errors (SE) as being quite large and overlapping between placebo and drug at least out to 36 weeks in pretty much all measures except the (carefully) selected few brain regions on slide 18. This would pretty much always mean a new trial required designed to eliminate those issues to hopefully get a solid statistical test of efficacy.
The percentages and P value you cite for the atrophy measures are just a misunderstood way of doing napkin calculations. The very low P value is firstly unreliable and secondly expressing a high chance that the very small apparent decrease in the rate of atrophy relates to a consistent, but very small absolute volume change achieved with Completer analysis and iffy statistics.
Should I buy back $AVXL now for over a dollar less than I sold a few days ago, or just wait till say mid Q4 and buy even lover hoping Anavex actually do file an MAA before year end?
I cannot recall having seen any Anavex published bar charts comparing A2-73 AD results to those from the Mab trials.
For reasons unknown, Anavex chose to not include comparisons to Lecanemab in their AAIC 2024 presentation.
I see someone posting a 3rd party bar chart. That may be what you were thinking of, but I tend do my own analysis from officially published data.
That does make sense and also implies that the very small absolute reductions (max a couple of %) in brain atrophy seen with A2-73 may simply correlate to how little amyloid plaque can be remove by some A2-73 increase in autophagy.
However, we haven't been given a measure for autophagy increase caused by A2-73 in the course of 48 weeks treatment. Only slide graphics illustrating what in vitro and in vivo cell studies show with some lab S1R agonist. Odd since now A2-73 is now touted as an autophagy through SIGMAR1 activation drug.
Looking at below chart and the quite dramatic dropout/no-data at week 48 compared with baseline, I think we have to take those result with a few spoonfuls of salt. The brain regions Anavex chose to show on charts are not the key brain region MRI atrophy indicators used as standard. Begs the question why Anavex did not show those.
You may be thinking of slides 25 & 26 from the Anavex April presentation.
It seems to me $AVXL closed near the low of the day, today!!!
I think Falconer will object to this as a fake story, when he reads:
Unfortunately the EMA and the FDA won’t listen to you and the other no it all WGT biotech‘investors’ here either. Of course there is also the precedence on this mb of failed predictions, including your own about the EXCELLENCE trial outcome.
Yes and don't expect any news - just the usual run down of all the catalysts Anavex still haven't achieved and listing the few that they have accompanied with a good helping of chocolate sauce.
The facts you got wrong you can check up on here:
And here:
That's all there is to the topic, which is that there are tolerability issues with administering A2-73. A good proportion may well be addressed by a different titration scheme, night time dosing etc., which the company have suggested.
No trials have been run yet that shows that these measures will work, produce less TEAEs and achieve statistically significant trial results per original protocol with ITT population analysis and accounting for any dropouts in the statistical methods used.
Whether EMA or other regulators will accept the existing trial results as registrational and then go on to issue some form of approval is yet to be seen. However, simply citing the Mab's risk issues, which are clearly real but by the FDA deemed manageable vs. benefit, is not the determining factor for approving A2-73. The Mabs were approved (only by the FDA) on solid data and statistics, but with an iffy balance of clinically relevant outcomes vs. risk. Anavex IMO currently lack the solid data, but may well in the end show a better risk/benefit profile.
My contention is simply that you got your facts wrong! and then you leap to another WGT theme of hating the Mabs, which doesn't help correct your initial mistake.
Yes what we are seeing, as has been pointed out here, is that the P2a Open Label trial was just too small to provide reliable results no matter how fancy the post hoc analysis was. From that Anavex then proceeded to design yet another too small trial to get more great signals again, but no cigar!
Yes it would but the company chose to blame Covid-19.
Complete BS response. Why couldn't just admit your WGT biased mistake instead?
Please see my reply just now to Hosai's post, with link reference for your convenience and memory recall.