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What? You got something against loki_the_bubba?🙄
That's the gist of it. Classy firm.
Ummm. Both trial arms led the participants to believe their daughters were getting the drug. The placebo response applies equally.
So, You're saying there's a chance?
Interesting article. 2-73 tics a lot of the boxes in the list of those that were approved.
Of the identified 210 NDA approvals in the observed time period, Johnston and colleagues observed 21 (10.0%) that included null findings for ≥1 primary efficacy end point; each of the 21 drugs were approved for unique clinical indications. More than half (n = 11 [52.4%]) were first-in-class approvals; 10 (47.6%) previously received an Orphan Drug Designation; 13 (61.9%) received an expedited review pathway from the FDA. Only 3 (14.3%) required an advisory committee meeting prior to FDA approval.
Knowing something will fail and evaluating something as having a possibility of success are not the same thing.
What The EMA did was look at the data presented and saying "this has a chance". So the EMA will take a full look at the data in an application.
As understand it in a two primary endpoint trial in most cases if one fails then the secondary endpoints are not calculated.
So in the Excellence trial since the CGI fail to meet its endpoint the secondary endpoints are not meaningful.
The trial design didn't suck. It was small number of subjects. The smaller the number of subjects increases the potential variability of the results.
Had there been say several hundred subjects and an even split between placebo and dosed subjects the probability of an unequal representation of mild and moderate Rett subjects in either the drug arm or the placebo arm would be reduced.
Having a larger number of subjects with a rare disease like Rett makes getting the required number of subjects in the trial more of a problem. It also costs more money and it takes longer to get the trail run. So trial design is always a question of tradeoffs.
The best trial would be to enroll every Rett girl on the planet. Then there is absolutely no question about how well the drug works. Of course that is not possible or desirable.
So a smaller segment of the overall population of Rett girls is enrolled in the trial. Now we have to use statistics to see how well the sample of the Rett population represents the overall Rett population. If the sample is very large then the sample is less likely to not be representative of the overall population.
Lets take the extreme case and just use 1 subject for the test. How do you know if that one person represents the overall population? It is unlikely that one person represents the the wide range of Rett impact on every Rett girl. So now we need to have more subjects in the trial to get a more representative sample of the overall Rett population. Here is where sample statistics come into play. The larger the sample the smaller the odds are that the people selected for the trial don't represent the over all population.
This is really what the p value is about. The p value indicates that if you took say 100 different samples from the overall Rett population that for a p <0.05 95 times out of 100 the results you get from the trial represent the actual drug effect and not some random bias in the trial by selecting only people that don't respond to the drug.
A placebo group helps to test the selection bias and other types of biases that can show up in a trial by hopefully having a placebo group that matches the drug group in as many ways as possible. The theory is that the two groups are equal and so the differences between them represent the drugs real effect. In most cases that is how it works.
However, just like the problem with selecting subjects for the trial, selecting subjects for the placebo group can have the same issues of the placebo group not being representative of the over all population and more importantly not exactly matching drug group. If the two two groups are not equal then that introduces a bias into the statistical analysis and you might not get true results.
Subjects are randomly assigned to either the drug group or the placebo group which hopefully eliminates any potential bias. But it is a random process which means it is not always going to be bias free.
Just like flipping a coin. Over many flips the coin will be about even number of heads and tails. But in a small number of flips you might get 10 or more consecutive heads in a row throwing off the appearance of a fair coin.
One of the more interesting examples of this was in a stat course I took. The instructor broke the class into two groups. One group flipped a coin 100 times and wrote the results on one board. Then on another board he had the students make up what they thought 100 flips would look like and he left the room saying that when he came back he could tell which group made up the number and which group actually flipped the coin.
He came back to the room and immediately pointed to the real coin group. When he was asked how he knew which was which, he pointed to the variability of the real coin flip. There were many more strings of head or tails in a row than in the made up group.
Statistics is never having to say you're certain.
It was a safety follow up issue. Like some of the subjects didn't make their follow up visit when they were supposed to. You assumed that it was an adverse event that need to be followed up on. Doesn't look like that was the case.
Your post crap is becoming tiresome. It is board noise.
Probably a bit soon to be talking about the demise of Rett. Today was certainly a set back. No question about that.
The FDA might still accept the totality of the data from all three trials or it might require an additional trial. Either way I doubt that Rett is dead.
This was top line data. There is still a deeper dive into the data coming. We won't know if the data is more supportive or less supportive until we see it.
Ummm. Placebo subjects don't get the drug so how does 2-73 kick it up a notch?
2-73 and 3-71 are in his area of interest. If either works out the drug will be useful in his practice. Also the MOA is new and has implications for CNS diseases which he treats. It also looks like he is a stock investor with some knowledge of investing.
Drs have disposable income to invest. I drink wine with several that are serious investors in stocks and wines.
Link doesn't work for me.
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.😱