Anavex Life Sciences Corp (AVXL)

[abew4me]

Yes. Excellent post. However, I disagree that they should wait for the Excellence pediatric trial before submitting an NDA for ADULTS. I feel that they have enough data with the Phase 2 and Phase 3 trials right now.

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From end2war's post:

It is admitted by Captain Missling that the CT.gov site was not updated in real time. This has started the communication problem. Now, we are all wondering about the full story.

And it is important for Shareholders to understand and appreciate what is happening so they can make decisions. So, the Captain needs to be clear and Missling has been very clear, so far, on the AVATAR results... safety and efficacy are discussed in the initial PR, and some issues regarding the subjective nature of the endpoints have been discussed and presented.

When AF raised his criticism, it was immediately denied that the endpoints were changed to "fit" the data; as the the Captain stated clearly the endpoints were changed before any data was delivered, and it was "prespecified" so that there is no disruption to the blinding of the trial.

We also were told that some conversations occurred with the FDA about this subject, which is to assure us that the FDA has not expressed any negative views and is supportive of the endpoints, which we now learn had been previously changed with approval of the UK and Austrailian authorities who had jurisdiction over the trials, since they were being conducted abroad in Austrialia and the UK, not the US.

As we now can see the chronology better, it is apparent that the endpoints were indeed changed properly; and the FDA was indeed informed, without any dissent or disagreement.

And we also know now why the endpoints were changed. It was because of discussions way before December 2021, with the FDA in which AVXL learned that the FDA wanted to see something less subjective than total RSBQ.

Kaufman is one of the authors on the paper reporting on ACADs endpoints, as I have previously posted. Those included the AUC math, and likely was part of the community of thought going on, which the FDA is well aware of and has approved. See the paper I posted previously: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550498/#

So, with knowledge of the issues being considered by the FDA, AVXL changed the endpoints for the study, and did that in conjunction with the regulatory bodies having jurisdictiion and authority under the foreign trials. This apparently happened all the way back when the study was first started. And the change to PH 3 presents no problem with the FDA as that is not something the FDA approves for a foreign study. What the FDA needs to decide is whether the foreign studies support an NDA if it is filed. And they will seek guidance on that. All perfectly correct.

In the recent CC, TGD was asked some penetrating questions by Duncan, which he was not fully prepared to answer. Recognizing that the story needed more details to be understood, they have filed a "supplemental" PR, which is the right thing to do, IMO. And, also, IMO, they have provided some of the key facts we needed to know, to Dr. Missling's credit.

At this point the shareholders might still want to know how the trials would have fared under the old endpoints, but that is not really relevant for immediate understanding of what has been achieved. It may come out eventually as a point of interest; however, it is not a question the FDA will need to have answered to determine if the endpoints were "prespecified" and free of unblinding.

Moreover, if the FDA wants to know that answer, it will be provided in the big package of data they will get with an NDA filing.

What we need to consider is whether AVXL will file an NDA with the FDA trying to use the current data from AVATAR for approval, or whether they will wait till the Excellence trial data is obtained to make a stronger case. I think they will decide how to proceed following the upcoming discussions with the FDA which will guide them as a Fast Track designee.

In my thinking, I tend to agree with Investor's latest conclusion that it will take all three studies, as I have been repeatedly arguing on the MB. But I still see the potential for the FDA to grant AA for the Rett's community. That is a developing story.

I keep saying, the best, and most safe course, likely will be to present all three studies, and the fastest way to get approvals will be to use the rolling submissing route IF the FDA concurs and will grant permission for that approach.

I think Dr. Missling may add some more color to the full story under questioning following the quarterly call on 2/9, and I am satisfied that we are on the right track for the essential problem of proving to the FDA that the evidence supports efficacy and the drug should be approved. GLTY.