"In Fragile X, new specific translatable and objective biomarker data generated with ANAVEX2-73 supporting the initiation of the potentially pivotal ANAVEX2-73 Phase 2/3 clinical trial will be presented at the 19th National Fragile X Foundation Conference taking place in July 25, 2024 to July 28, 2024."

[Later, in reply to a Tom Bishop question:]

"Yeah. So this is very intriguing data. It’s a biomarker, which is measurable both in patients, in humans, as well as in animals. And it’s correlating very clearly, it has been published to the pathology of Fragile X or to showing a reduction of the pathology of Fragile X.

"And this will be presented for the first time at the conference in July and we’re very excited about it, because it strengthens the, first of all, the evidence that Fragile X is an extremely good indication for blarcamesine for ANAVEX2-73, but also it would give us in a clinical trial, a biomarker, which is so important in CNS, which is hard to find biomarkers of a pathology. So these are the two reasons why we’re very excited about this presentation coming up."

Tom Bishop

So you could move into a potentially pivotal Phase 2b/3 trial, just based on your biomarker data to date, is it?

Dr. Christopher Missling

"Yeah. So that biomarker data we presented will also -- we also -- yeah, we have to also appreciate that there are physicians, patients, advocates group who want to learn why would you -- why want to be part of a trial? And this information would give somebody that information to say, to be excited about being part of a trial because of the fact that it would define the chances of being beneficial to a Fragile X patient in real world and that’s what this biomarker data will -- would be to get the excitement in the community to also then have a smooth enrollment and trial execution, which is important."

Well, my Yahoo chart shows 212 thousand shares traded exactly at 4:00pm at $4.50. sab (Steve), who worked for years in brokerages, has said we will gain no insight by thinking about the big trade volumes of the last minute of the day. They've always been a mystery to me.

Is it not equally likely the MMs are trying to keep the stock price high (say around $4.50 instead of $3.50) so they can fill large sell orders from institutions at better prices? I prefer your scenario, but I don't see why it couldn't cut both ways.

Do you have any reason to believe Anavex has more such "stuff happening" than most other biotech companies?

k9uwa and LakeshoreLeo: I read k9uwa's post that the law firms had no lead plaintiff and thought "Great!" Then I read Leo's post about a new lawsuit. I guess I should put my own effort in on the lawsuits like I have in understanding the clinical trials, but I'd really prefer and appreciate anyone catching me up on the lawsuits! It has seemed to me that lawsuits would be a harmful distraction but even if they had merit*, any potential damages would be dwarfed by the company's income should it get an Alzheimer's regulatory approval. Still, I'd like a brief summary of what's going on on that front. (I haven't paid much attention lately as I've felt there's not going to be much new to discuss while we await the peer-reviewed article and submission of the MAA.)



*Personally, I thought the Rett claim was ridiculous; I never read a claim based on CTAD 2022, but I do believe Anavex could be liable for misleading investors back then -- including me, though I have no interest in helping the suit along.)

What's the latest with the securities lawsuit?? I haven't been around for a while, but as I recall May 13 was supposed to have some meaning as the vulture law firms had to have a lead plaintiff by then.

It appears Anavex did not pay for the article, as, at the end of the article, it says: "Disclosure: Insider Financial and its owners do not have a position in the stocks posted and have posted this article for free without editorial input. A guest contributor wrote this article and solely reflects his opinions."

OTOH, the publication's disclaimer sure makes it sounds not-legit to me, particularly this sentence: "Our reports/releases are commercial advertisements and are for general information purposes ONLY."

I looked at just one of Sandburg's other pumped stocks, which I chose at random and because he had many articles about it*: $TOMDF. Yahoo finance shows its share price as $0.00. It announced insolvency a while back: https://finance.yahoo.com/quote/TOMDF

Regardless of what he says about Anavex (which on a quick skim seemed a good take on the bull thesis), I trust neither him nor the website.

I do wonder if the article is the reason for the price jump, or coordinated in some nefarious way with a stock trader, or just coincidental.

* https://www.insiderfinancial.com/author/chris-sandburg

Anavex YouTube: Noble Capital Markets Healthcare Conference - April 18 2024. Thanks to DaveV-1 for posting the embedded one; it's hard to find. The link below offers a better way to view it. It works in my browsers but not in the YouTube app.

Put https: in front of the the character string below, and paste:

//www.youtube.com/watch?v=b5uoWiBshsA&t=1779s

The FDA's previous Draft Guidance for Alzheimer's (2018) can be downloaded at
https://www.fda.gov/files/drugs/published/Alzheimer%E2%80%99s-Disease---Developing-Drugs-for-Treatment-Guidance-for-Industy.pdf

The link to download the 2024 Draft Guidance can be found here:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/early-alzheimers-disease-developing-drugs-treatment

The differences between the February 2018 and March 2024 drafts are actually quite subtle. By 2018, the draft guidance already recognized the problem of measuring progression of functional deterioration in early Alzheimer's; that did not begin with the 2024 draft. To understand the differences between the drafts and what the drafts portend for a review of blarcamesine would require careful parsing of one against the other and a good understanding of the FDA's "Stages" of Alzheimer's and in which of those Stages the P2b/3's subjects belong. Since the drafts don't reference any test numbers, like for ADCS-ADL or MMSE, it's hard for me to make that assessment.

Also, both drafts loudly announce

The 2018 draft went 6 years without being "implemented" and was then replaced with a new draft. I don't know how to interpret its level of influence in the agency.

I called the IR number about this a few weeks back and Clift told me he was not at liberty to say.

We don't even know if the promised journal article has been accepted anywhere.

I wasn't around for the Reddit/GameStop-style upswing, but I get that it was just meme stuff and pumping. My guess is that most the shorts believe Anavex is going down because of fundamentals, though I greatly hope they're wrong. I don't see Reddit and short sellers of that stripe as comparable.

My pretty-certain-I'm-right guess is that on any day a stock has a very outsized volume, much of the trades are churn. Crescent was wrong when he initially said all the shares sold were stockholders dumping. But it's the same when Boeing, after weeks of daily volume averaging <5 million shares has a 40 million share day right after a window pops out during an Alaska Air flight. It isn't that all 40 million shares were dumped; MMs are also selling and buying all day, as are traders; there's churn. But on balance, many were worried about a further price decline and sold. A problem like the window occurrence is just a bad hiccup for Boeing, which isn't going to stop selling planes. Pre-revenue Anavex had a presentation about its lead drug for its most important indication that was, on balance, poorly received by knowledgeable biotech investors, and there was selling pressure over the next days. Shorts expecting further price declines doubtless jumped in, too, but it was the red flags in the top-line results that triggered the selling (and shorting) and kept the price low subsequently; those red flags were the reason investors didn't swoop in later to take advantage of the "bargain."

As for the hard facts, according to Yahoo Finance, there were "only" 45 million shares traded December 2, and the share price rose that day. On the 5th and 6th it declined, on 8 million and 6 million shares.
https://finance.yahoo.com/quote/AVXL/history?period1=1669593600&period2=1670457600&interval=1d&filter=history&frequency=1d&includeAdjustedClose=true

BTW, you might note from my recent posts that while I think the original P2b/3 PR and presentation were very flawed, I believe the situation has evolved very positively. It's the same trial, of course, but the March FDA draft guidance, the biomarker results, and Anavex's change in how it presents the clinical results makes the early history pretty much inconsequential as to chances for drug approvals. The CTAD past is becoming increasingly irrelevant.

I'm not sure what you would like elucidated.

For in depth on what was wrong with the CTAD presentation, you might look for comments by Doc, Investor, and frrol from the week following the December 2, 2022, presentation. It's been discussed a lot on this board, including later but it's hard to recall just when. (I wasn't on this board until February last year. I first invested in 2021.)

There are people, such as Boi, who argue that the shape of the results from the P2b/3 call for a statistical approach other than comparison of the means. I don't buy it. It's hard to impossible to find clinical trial results of approved drugs for endpoints on a graduated scale like ADCS-ADL that don't include comparison of the means. Binary results, like died-vs-didn't-die, are a different story; they may rely on Odds Ratio. There are other people who say one had to accept that the endpoints were met because Missling said so and it puts his ass on the line legally to have said so. I don't buy that as a "reason." I think things got screwed up because they had only one day, at most, before the scheduled CTAD presentation to review the data they got from the CRO, and afterwards they were in a difficult position to backtrack. The CRO, not Anavex, did the statistical analysis initially. Kun Jin's reworking of the results last September omitted any mention of ADL; I take that as an implicit admission that ADL is problematic. For why I called the December 5 cc pathetic, listen to it and judge for yourself. Better yet, listen to it after learning what critics of MacFarlane's presentation and the PR said; Missling never addresses most if any of their issues. Instead he spends his time asking respected doctors if their patients would prefer getting an infusion in a hospital or taking a pill at home.

Doc328 and Investor2014: I'd appreciate your feedback on my current belief that blarcamesine's chances for approval to treat Alzheimer's has become excellent. I initially thought its chances were excellent after MacFarlane's CTAD presentation, and I was wrong. I was a total newbie with respect to biotech investing at that point. You two and frrol were the primary people who opened my eyes to the problem. I have no illusions that I've become very knowledgeable, but I understand a lot more now. More importantly, Anavex's statistical approach has changed; it has published some new, very promising biomarker results; and the FDA has indicated it's changing the goalposts for Alzheimer's in a way that I believe eliminates the biggest barrier to the approval of 2-73.

Before the September 14 PR from Anavex and the March draft guidance about Alzheimer's trials from the FDA, I believed 2-73 was likely to be disapproved mainly because the FDA would require that the ADCS-ADL results be clinically and statistically meaningful, and Anavex didn't have the goods. You guys, my own research, and my biostatistician friend convinced me that the expected, best, and exclusive (or nearly-exclusive) way to show the ADL results was with a comparison of the means. It was extremely suspicious that Anavex provided no means tests results for ADCS-ADL. Providing an Odds Ratio could have bolstered the ADL results, but it couldn't serve as a total substitute. Failure to provide n (the number of trial subjects who crossed the threshold used in the Odds Ratio) was also very suspicious and greatly undermined the utility and persuasiveness of the Odds Ratio.

It seems to me ADL no longer is a problem. The FDA's draft guidance from March indicates they are willing to ignore inadequate ADL (and other similar functional endpoints) results in trials using MCI and early Alzheimer's subjects like the P2b/3.* It's a draft, but it seems very unlikely the FDA will back away on this change.

The CDR-SB and ADAS-Cog results were strong enough and, as pointed out in what I call "Kun Jin's <0.025 p-value finesse," very solid on their p-values.

The safety of the drug (which I believe Doc has consistently undervalued) and the ease of administering it without cumbersome, expensive tests and facilities (which are far from ubiquitous outside major metro areas) weigh heavily in blarcamesine's favor.

The new draft guidance has also shown an openness to considering biomarkers other than amyloid and tau, whether validated or not so far. We didn't until recently see some critical biomarker results from the P2b/3. The p-value for 2-73 counteracting brain shrinkage was extremely impressive (P = 0.0005). According to someone on the internet who claimed to have attended Grimmer's recent talk in Lisbon, "there is nearly complete prevention of grey matter loss" -- not the most reliable source but he seemed legit and it fits with the p-value. Additionally, the graphic of brain shrinkage differences between placebo and blarcamesine by brain region correlates properly with the regions of shrinkage most affected by Alzheimer's. I'd be very surprised if the FDA would not look very favorably on blarcamesine's effect on brain volume; it seems the type of additional biomarker the FDA would be looking for under the new draft guidance.

Likewise, the plasma Aß42/40 ratio measurements were good, and, even though that might not be the ideal, expensive validated mode of measurement, it has been shown to correlate strongly with the validated mode. Maybe the blood-based and CSF measurements used by Anavex will get validated. In any event, the draft guidance gives a boost to the FDA giving them more weight as surrogate biomarkers.

The only pothole I see is that results didn't clearly indicate best dosage. I don't see this as the big stumbling block Doc has said he sees it to be. Considering the safety profile, I think (admittedly without knowledge or experience) the dosage issue shouldn't be a great concern. Even for many drugs on the market that pose more serious health risks, doctors adjust dosage over time based on lab tests, clinical exams, and patients' subjective feedback. Why can't a doctor start the patient on the lower dose used in the P2b/3 and adjust over time, as is done with many drugs?

In sum, as I asked in an earlier post, If you remove the P2b/3's ADCS-ADL results as an issue -- which the FDA's new draft guidance effectively does -- and you consider just the CDR-SB and ADAS-Cog results, which are good (and have solid p-values), not to mention the biomarker surrogate endpoints like brain-region volumes and the amyloid beta ratios, what's not to like? (I'm asking you two specifically because you both seem to remain very skeptical about the drug's chances despite what I see as major, extremely encouraging developments; and, of course, I value your thinking. If anyone else, especially those inclined to think critically, want to weigh in, then, of course, please do!)

*

I cannot tell for sure, but it seems to me that all the P2b/3 subjects (as well as the ones used in the lecanemab and donanemab trials) were in Stages <4, probably even "early 3" and below.

I agree with the heart of your argument. For someone who was knowledgeable about clinical trials, MacFarlane's presentation would have raised red flags. Specifically, for the type of endpoints in those trials, Odds Ratio was a very peculiar choice, especially since there were no numbers reported about how many of the trial subjects crossed the threshold used for calculating the Odds Ratios. The reddest flag of all was the failure to include a comparison of the means for the ADCS-ADL endpoint. I believe these are the reasons Doc328, for example, sold his shares. Furthermore, the December 5 conference call was pathetic and did not confront the doubts raised by critics, including Feuerstein. I think Feuerstein is a schmuck, but not all his criticisms of the top-line results release, IIRC, were bull.

I think, OTOH, you're mistaken in saying 75% of the shares were sold off over those days, as that doesn't account for churn. You're right, though, that it sure showed people were generally not wowed by the CTAD presentation. Had they been, buying pressure would have overwhelmed any supposed short-seller manipulations. On balance, many shareholders dumped lots of shares.

You and I are in the same boat. I bought a lot of shares in the premarket the morning after the CTAD presentation. Having watched the CTAD presentation and read the PR, and lacking critical understanding about clinical trial results, I believed the company had a clearcut route to approval for the most significant Alzheimer's therapy to date, and I wasn't going to wait until the stock skyrocketed during regular trading hours. I paid about $14/share. You've said that "in the end" you "may look really stupid" for not selling on December 5, 2022. Let me tell you, you already do! As do I! I prefer to see us as having been inexperienced in judging trial results, at least when the sponsor says the results are great and all endpoints were met. It wasn't until at least April 2023, IIRC, that I first understood what was wrong with the results, by which time I felt I'd lost too much money to just bail out, and I thought there might possibly be light at the end of the tunnel, at least with Rett.

I believe you and I would make ideal lead plaintiffs in a securities suit based on the CTAD presentation, but I'm not going to volunteer to do that. I wish the lawsuits would just disappear. (BTW, in contrast, I see no basis for a lawsuit based on the Rett results and PRs.)

I also want to include here, that I think Anavex's shot at approval is better than at any previous time since I've been involved. The combination of "Kun Jin's <0.025 p-value finesse," the recent biomarker results such as regarding brain volume, and the FDA's draft guidance negating the import of the ADCS-ADL endpoint, seems to me to make the P2b/3 trial results an excellent basis for approval. I wish, of course, that I'd sold on December 2 or 5, and that I were doing my AVXL purchasing now. I've sold over half my shares, very belatedly and at a big loss, but I still have a substantial amount. If I didn't already own "enough," I would now, in light of what I said earlier in this paragraph, be buying more.

BIOChecker: I'm curious. Can you provide a brief explanation of why Northwest Bio has a tainted reputation? At least it's filed for UK approval of its glioblastoma therapy (and had a 25% SP drop since filing!). The top-line results for its last trial looked comparatively good to me.

Two of my friends died from glioblastoma. For one of them I helped his wife look into the possible post-surgery therapies, and I was on the side against doing any of them. (She knew how little I know, it wasn't like she looked to me instead of her doctor!) His tumor was so aggressive the doctors weren't predicting much life extension from intervention. I regarded the "cure as worse than the disease" for the amount of time they had left together.

Our FDA does do that for accelerated approval, as I stated. Are you saying that you know for a fact the FDA does not do that in any other circumstance? That's what my post/question was about.

I know the OLE enrollment numbers are excellent, and I'm not saying the drug doesn't work on Rett. I do not believe the FDA would find that OLE enrollment percentages outweighs what I think must be quite bad results for the three most important clinical efficacy endpoints such that it would grant full marketing approval. I was looking for another way to get the drug to market despite the bad statistical results for those endpoints. (Do you think the CGI-I and ADAMS were good results? I doubt you do.) Maybe data from results of the OLE will influence the FDA, just like we hope there are good OLE results from the P2b/3 extension for Alzheimer's. I don't think enrollment numbers in themselves will.

It's fine, of course, that you had something to say about the lawsuit, but I hope you understand I wasn't talking about it at all.

Is there any chance the FDA could approve conditionally marketing 2-73 for Rett while a Phase 3 proceeds? I usually think of that approach in the context of accelerated approval where a significant biomarker has shown efficacy despite iffy clinical trial results; but that's not what we have here.

Inclining against approval of any kind without a new P3, is the fact that the overall results are probably worse than the RSBQ results that Anavex and this message board have been focused on. The January 2 PR provides the "LS mean difference" statistics only for RSBQ. For the other two clinical endpoints, Anavex did not provide any numerical results whatsoever. For one, all it says is, "The other co-primary endpoint, the Clinical Global Impression – Improvement scale (CGI-I) ... was not met." For the other (ADAMS), it says only that it "trended favorably." Again, no numerical results whatsoever.

I find this hide-the-ball approach to releasing top-line results confidence-killing. Just bite the bullet and release the numbers! I think one has to surmise the CGI-I and ADAMS numbers are quite bad. My guess is that CGI-I did not even trend favorably (otherwise Anavex would have said so, like it said about ADAMS) and that the ADAMS results were considerably less positive than the RSBQ results.

On the positive side are the superior safety and side-effect results, the anecdotal evidence, maybe a reduced frequency of seizures, the adult Rett trials results (though maybe controversial), and the sad current SOC.

On balance, my guess (it's a guess because Anavex has withheld numerical information that I believe usually is released in a TLR) is that the EXCELLENCE clinical results are too poor for the FDA to grant any kind of approval for Rett pediatric use until it has seen much better results from a new Phase 3. But I could be wrong about the clinical results' persuasiveness. So I'm interested to know: Is there any precedent or administrative rule indicating the FDA could approve conditionally marketing 2-73 for Rett children while a Phase 3 proceeds?

True, though the problem may have been reduced by having the n divided up 1:1 instead of 2:1 drug:placebo.

Smartphone app may pave way to treatments for frontotemporal dementia in under-60s
https://medicalxpress.com/news/2024-04-smartphone-app-pave-treatments-frontotemporal.amp

Compare this to my earlier post about using wearable gadgets instead of in-clinic tests to make more accurate, finer measurements of disease progression in clinical trials:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174120052

Time to get going on 3-71 for frontotemporal dementia!

Heck with the EMUs! Don't forget the CHiMP!

That article is new. But today on Twitter they also posted the one I linked to here:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174159075

Both are supportive of the MOA (and potentially point to a whole lot more indications the Anavex molecules could possibly treat); one article is new and one isn't.

I have no idea. I find it odd the company is posting them on LinkedIn. Twitter seems more the norm. Instead of 2001: A Space Odyssey graphics, I think it would be more useful to include clickable URLs. I sort of like the graphics, but they also seem hokey. I get why they would announce recent articles on Twitter, but not why they make these brief announcements referencing articles from five years ago.

I don't know who they consider the target audience.

OTOH, the content of these articles is very relevant to what the company is doing, the gene pathway info and MOA they've been elucidating, the indications blarcamesine and 3-71 are aimed at, etc.

EDIT: Maybe it's the serialized graphic novel version of the peer-reviewed paper!

There are two new Anavex posts on Twitter. The one on LinkedIn announced by plexrec and this one:

It links to an article from 2019:
https://pubmed.ncbi.nlm.nih.gov/29127580/

URL for the article referenced by Anavex on LinkedIn today:

From autism to Alzheimer's: A large-scale animal study links brain pH changes to wide-ranging cognitive issues
https://medicalxpress.com/news/2024-03-autism-alzheimer-large-scale-animal.html

Link to Anavex's post (commented on, BTW, by Mayomobile/Jesse):
https://www.linkedin.com/posts/anavex-life-sciences_anavex-biopharma-neuroscience-activity-7180899669747585025-0zp9?utm_source=share&utm_medium=member_desktop

Unexpected fact: Cocaine is a Sigma-1 agonist. (I don't believe it's been trialled much in any of the indications on which Anavex has been focused. ;) )

I just came across it scanning the article Anavex linked to earlier on Twitter:
Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293995/

Since I do, I'll have to say I don't! (Steady, this is already so quickly convoluted, I don't know if I should thumb-up your post or not. :) I did enjoy it.)

Here are the links (foolishly) put in a not-clickable form in a graphic in Anavex's tweet today:

Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293995/

Accumulation of 'junk proteins' identified as one cause of aging and possible source of ALS
https://medicalxpress.com/news/2024-03-accumulation-junk-proteins-aging-source.html

Ridiculous overstatement:

I take it you're referring to the draft guidance that came out in March. It says that functional measurements such as Activities of Daily Living aren't necessary endpoints for clinical trials in AD, that surrogate biomarkers will be relied on more, and it would welcome support for additional biomarkers. There is nothing about Sigma receptors or anything else unique to or limited to Anavex. Anavex is not the only company working on drugs that are not MABs, and the guidance does not even disown the utility of measuring amyloid burden. Unless you explain what you mean by "the Anavex theory" and precisely how the guidance connects with it, the sentence quoted above is just WGT emoji-bait.

I would love for what you say to be accurate. If it is, please provide real support. I think the new guidance is great for Anavex, and possibly for the approval of other Alzheimer's drugs, but I expect you've gone way over the top.

I have him blocked, too. I saw his post only because it was a reply to someone I don't have blocked (plexrec).

Extreme Zig: If you remove the P2b/3's ADCS-ADL results as an issue -- which the FDA's new draft guidance effectively does -- and you consider just the CDR-SB and ADAS-Cog results, which are good (and have solid p-values), not to mention the biomarker surrogate endpoints like brain-region volumes and the amyloid beta ratios, what's not to like? Do you have any support for your crack that "You have to have good results first."? I can think of only one remaining problem with the results, and I don't believe it would stop the FDA from approving. Step right up and tell us all your reasons why the results aren't good (unless, of course, you're simply trolling).

Look at my earlier post* and Steady's reply to me and then my reply to him.

* https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174137584

The reposted tweet was not from just some "other biotech" -- it was from Ariana Pharma, the French company that has done the AI-based genetic pathways analyses for Anavex trials.

We're pretty much in sync on all this. I agree that the new (draft) guidance indicates a path for a later trial relying on biomarker endpoint(s) in Stage 1 subjects with no cognitive or functional endpoints at all. I read this document also to be aimed squarely at trials for Stage 2 and 3 subjects, which will greatly help an NDA based on the P2b/3 since it eliminates the need to satisfy any functional endpoints.

I entirely agree that the draft is "a call to the medical establishment to find and validate new AD biomarkers and [that] it indicated a willingness of the FDA to consider new AD biomarkers."

Maybe the blood-based and CSF measurements used by Anavex will get validated. In any event, this draft seems to give a boost to the FDA at least giving them more weight as surrogate biomarkers. There are journal articles that ought to incline the FDA to validate brain-region volumes, e.g., https://link.springer.com/article/10.1007/s13760-023-02235-9, which concludes,

Link to the Anavex repost by Mohammad Afshar:
https://www.linkedin.com/posts/mohammad-afshar-97a2041_early-alzheimers-disease-developing-drugs-activity-7177949583430287360-4DqW/?utm_source=share&utm_medium=member_desktop

Text of it:
The newly issued FDA's draft guidance for developing drugs against Alzheimer's, a first update since 2018, paves the way for the extensive use of Artificial Intelligence and modern biological tools that are linked to our molecular understanding of the disease progression.

Promoting the use of patient selection biomarkers the agency notes that "It is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials". Furthermore, it establishes that "Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval".

Within this framework, the power of eXplainable Artificial Intelligence tools combined with the broad availability of multi-omic data for a large number of patients will likely fuel the discovery and validation of truly novel biomarkers, providing the quantum leap needed to combat this disease.

This novel framework that guides the discussions between drug makers and the FDA is likely to further accelerate the pace of innovation for Alzheimer's patients, building on very recent successes.

Jacques Touchon Federico Goodsaid Hichem C. Thomas TURCAT Frédéric Parmentier Véronique Chabernaud

#FDA #ALZHEIMER'S #PRECISIONMEDICINE #AI #BIOMARKERS #GENOMICS
Early Alzheimer’s Disease: Developing Drugs for Treatment
fda.gov • 20 min read
Clinical/Medical

I think the biggest change is the demotion of measurements of functional effect of the drug.

The P2b/3's biggest weakness was with functional efficacy, specifically the ADCS-ADL results. The trial's subjects were pretty much all in Stages 2 and 3 as far as I can tell. I read this as saying ADL results will no longer be a hindrance.

Additionally, the draft shows great openness to relevant AD biomarkers, and looks to having more of them than just amyloid. I'd be very surprised if the FDA would not look very favorably on blarcamesine's effect on brain volume; it seems the type of additional biomarker the FDA would be looking for under this new draft guidance.

Even though it's not final, I think this draft almost certainly indicates the direction the FDA is heading with regard to evaluating clinical trial results for Alzheimer's disease. I think it bodes very well for blarcamesine's chances.

All true. There's no necessary negative implication, but I really can't imagine a positive one.

He hasn't necessarily sold yet and may not. But your interpretation seems farfetched to me. If he just pays for the options he was contractually entitled to and keeps them, there's no implication of self-dealing.

I find it very hard to put a positive spin on this. Since a Form 144 doesn't obligate him to sell, I guess you could say he's just keeping his options open (no pun intended). But that's far from a really positive spin.