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You raise good questions. This was a top line report. That means it is a quick look at the data at a high level.
Next level is a top line result report which is a deeper dive into the results. Then there will be a full data report, typically in the form of a peer reviewed paper or a full report from the company.
At this point we have no real data on the seizure data. We have three anecdotal reports i.e. real world experience. We don't know if there were only three that had a significant reduction in seizures or were there a large number of girls that had a reduction in seizures. How many saw a reduction in seizures and by how much they were reduced are the key factors.
Question #1. The trial population size was small. Avatar was with 33 subjects. Most likely the FDA would consider that too small to be pivotal trial. Anavex can ask the FDA about that. The worst they can say is run a bigger trial.
Question #2 The EMA will not see the Rett trial data. That is for a different indication so it is not relevant unless there were significant safety issues which there were none.
I also expected the pediatric Rett trial to be a success. It was not the clear success I expected. I gave a 99% probability. Now I give it 55% and that may require an additional trial.
Depending on what the FDA says when Anavex gets its meetings I think that Missling may give up on the voucher and go full speed ahead on AD.
There is a lot of the NDA that I hope Anavex has been preparing for Rett that can be directly used for the AD NDA. If Missling decides to go full speed on AD I expect to see an application for AD priority review to the FDA.
We shall see. My guess is how Missling chooses to proceed depends on the FDA guidance on Rett.
Not when Anavex received the CRO report, but when Anavex finished checking the CRO report numbers and doing its own additional calculations.
That's the future. We are dealing with the current situation. This is only the top line data report. The top line results will come out and may paint a different picture. Whether it will be better or worse is an open question.
It can take up to 60 days to get a meeting scheduled with the FDA for them to provide guidance on how to proceed with these Rett trial results.
Anavex will want to have a full analysis in hand before it goes to the FDA.
What the FDA has to say about the full results will determine how Anavex proceeds. The FDA could recommend filing an NDA, running another trial, or abandoning Rett indication. Based on the small adult trial size I doubt that the FDA will recommend filing for adult Rett only approval.
The gene data shows that the drug has an effect on the gene expression. What it doesn't show is whether those changes result in a beneficial outcome.
Unless there is data to show that the change in gene expression is linked to a specific outcome it can not be used as a bio marker.
What are they going to sue over?/ Trials are not guaranteed outcomes. That is why they are run.
Dr. Jin can not change the results of a trial. The data is what it is. He can make sure that the proper statistical tests are applied and carried out correctly.
The PR was pretty clear that the EMU had approved Anavex filing for a centralized marketing process. That means the approval will apply to all EU countries. The other path is National Authorization procedures where each member state has to authorize the medicines for use in their own country.
That is the first step in the long chain of events leading up to an MAA filing.
The next step is sending a letter of intent to file an MAA. That letter will specify a date on which Anavex intends to file its MAA. That date has to be 7 months before the intended submission date. During that 7 month period the EMA selects the Rapporteurs who will evaluate the MAA.
https://learning.eupati.eu/mod/book/tool/print/index.php?id=893&chapterid=822
Obtaining the approval for the Centralized marketing procedure is significant step for Anavex.
However, before a medicine is made available to patients in a particular EU country, decisions about pricing and reimbursement take place at national and regional level in the context of the national health system of the country.
The company has not said anything that suggests is has filed it's required letter of intent.
So, without any evidence that such a letter has been filed I do not claim that one has been filed.
Do you have any evidence that they didn't?
..., whereas I assume LOI already sent given the CHMP ok to file status.
That is not what the PR said. I copied the paragraph in my post.
Where is the letter of intent?
Do you have any evidence of that?
All the company has PRd is the agreement to allow for submission under the centralized marketing procedure.
NEW YORK, Dec. 19, 2023 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, announced today that the Committee for Medicinal Products for Human Use (CHMP) within the European Medicines Agency (EMA) agreed that oral blarcamesine for Alzheimer’s disease is eligible for submission of an application for a Union Marketing Authorisation in the EU under the European Medicines Agency’s centralised procedure./quote]
Apparently you haven't read the timeline you linked. 7 months after submission of letter of intent before the MAA can be submitted.
Feb'ish is not an option.
As the porn star said "I'd rather be long than short." Happy New Year.
Given Missling's communication style, predicting what Missling will or won't PR is a chancy bet.
I think we can safely say that if Anavex has started the rolling NDA it would have been announced.
Getting an approval to file an MAA as a centralized marketing application is not a material event.
The company chose to PR that approval. It was not required to do so.
Edit, reply to later posts.
An agency decision on an NDA or MAA is a material event because it has significant financial impact on the company which ever way the decision goes.
If the decision is no approval that means the write off of all the development costs. If it is an approval it means likely significant revenues in the near future.
Starting a rolling review for Rett is not a material event. Not even close.
Happy New year to All.
May this year bring happiness and good health to all the board.
May this year bring 2-73 to the girls suffering from Rett syndrome.
The FDA does decide approval. And, the FDA takes real world experience into account when deciding on approval i.e. anecdotes.
What we know is that whatever data Anavex showed to the EMA they thought it good enough to indicate to that Anavex it should move ahead with the MAA process.
That does not indicate that Anavex has submitted a letter of intent which specifies an intended date to submit an MAA.
Given Missling's habit of not sharing information, making any assumptions about where Anavex is in the letter of intent process is a risky guess.
Actually credibility is important. Turns out delivering on approvals is more important in Anavex's case.
At this point in time Missling's credibility is based on timelines proclaimed by Missling and he has not done very well on delivering on his self established timelines. That is clear to all.
Delivering on approvals will reestablish Misslings credibility way beyond the missed timelines.
So at the moment Missling's credibility has taken a hit. I suggest this is a short term problem. If the company fails to deliver approvals then Missling's credibility takes a massive long term whack.
If the company obtains Rett approval Missling will be suddenly rehabilitated. If the company obtains AD approval the history of Missling's credibility will be completely rewritten with the benefit of hindsight.
The story is still being written. How the 4th act plays out is still a mystery. You invest your money based on how you evaluate the incomplete information.
The Lecanemab study had only one primary endpoint so it is not quite comparable to the AD study.
The Trofinetide study did have two endpoints however it did not specify any alternative methods of statistical testing. It required both endpoints to meet p<0.05 to proceed to testing the secondary endpoints.
Thank you for linking those two documents.
Thank you Ricardo Cabeza.
$2,294,480 will buy a lot of Big Macs. It might even cover a haircut.😱
A belated Merry Christmas and a Happy New Year to all.
You could explain rather than just throw rocks.
There are ways to control for multiplicity. I think that in the case were are discussing that is why the p requirement was tightened up from p<0.05 to p<0.025 for both the primary and secondary endpoint.
Having never seen a SAP I'll take her word for it.
Multiplicity is mostly aimed at ad hoc analysis. If the alternate analysis is specified in the SAP it is not an ad hoc analysis. However, as I pointed out above, the p requirement is tightened up in the alternative analysis.
It's a chance I'm willing to take.
Ummm. The argument isn't if one of the two primary endpoints achieves p<0.025 but one endpoint passes with p<0.025 and the secondary endpoint also achieves an endpoint of p<0.025.
A crucial detail in this discussion.
The trial is successful in meeting the co-primary endpoints if the significance of each endpoint is P < 0.05, or if the significance of only one co-primary endpoint is P < 0.025. If only one primary endpoint is significant at an a level of 0.025, then the secondary endpoint will be evaluated at the same level of 0.025. The trial was successful, since the differences in the least-squares mean (LSM) change from baseline to 48 weeks between the blarcamesine and placebo groups were -1.783 [95% CI, -3.314 to -0.251]; (P = 0.0226) for ADAS-Cog13, and -0.456 [95% CI, -0.831 to -0.080]; (P = 0.0175) for CDR-SB in patients with early Alzheimer’s disease.
I'm sorry. Those two things seem to say the same thing to me.
Interpret his comments as you will.
I was going with what was stated rather than what could be inferred. You may be right.
Instead of criticizing my understanding, how about enlightening me and the rest of us poor ignorant folks with what the SAP says.
What I am saying is they probably took Anavex's word for stat significance. Maybe glanced at the numbers to see if they passed a smell test and went on.
You are making several assumptions in this statement that may or may not be true.
What Missling said was that the EMA has seen data that has not yet been published. Whether that is the "full" data or not is unknown.
Second, I doubt that the EMA did a technical review. The EMA has not appointed the subject matter experts yet. I get that that they do have staff people that are competent to look at what Anavex presented and understand what they are seeing. I doubt that the staff did a technical review in the sense of a deep dive into the data presented. More likely the staff looked at what Anavex presented decided that it looked reasonable and OK'd moving on to a MAA where a full technical review will take place. The staff may have even said this looks very good. Either way, it is the MAA process where the deep dive into the data takes place.
You statement implies that you are currently in a loss position on you AVXL investment. Sorry to hear that.
If you are not in a loss position and you feel that management is that bad why would you choose to ride it out? That implies some expectation of a more profitable outcome. What am I missing here?
Not sure that you are missing much worthwhile.
Really? When did the company report that number?
The one that that wasn't stat sig is ADCS-ADL!
Doesn't matter where the Odds Ratio ranks in the SAP, if such a ranking exists. Meeting trial criteria is a binary event. The trial meets the criteria or it doesn't. If there are multiple ways to meet trial criteria, it doesn't matter which one the trial meets.
By way of analogy, you can win a football game with nothing but field goals. What matters is that you have one more point than the other team.
Hmmm. The key phrase is "Notify EMA of the intended submission date (letter of intent)"
The letter of intent starts the 7 months clock.
Submission of the eligibility request can occur 18 to 7 months before MAA submission.
I went back and looked at the PR and it talks about approval for Centralized Marketing application.
I can't find anything specific about a letter of intent in the PR or the CC.
Bottom line is you are probably correct.