This is exactly anyone should have paid attention to: endpoint changes which I would prefer endpoint adaptions.
It has been a tedious process back and forth between the company and the four RAs, and this process has now bore fruit: UK and Germany have bee onboard with company's request for endpoint adaptation.
Nonetheless, we have not seen FDA doing the same; otherwise I have seen no reason that the company has not PR or updated US clinicaltrial register.
I guess if that's the case, it is still better the company should work hard to persuade the FDA to onboard now -- this is the goal the company should aim with the utmost priority, to have some trouble now and guarantee smoother success later!
In a logic thought, the company should PR endpoint changes/adaptations first before announcing top line data.
So on possibility is that the company may elect to be still blinded and let FDA access or instruct statisticians to report directly to FDA and let FDA more informed before it can make a decision.
However, by no means FDA's nod or not is not required by the law, the company can still be unblinded and report top line data, and later submit BLA to FDA for approval, and let data to speak for itself, but obviously this will not be the best way forward.
So it may be that the company initially anticipate FDA's nod/buying in would come shortly after 5 October so that all the conference presentations could go forward as planned, but for whatever reason, this process still needs more time.
Besides waiting for FDA's buy-in for the adapted endpoints, there may be other regulatory process on going which could include early approval if FDA gets unblinded data, etc.
To sum it up, the best scenario is that the company can get FDA's buyin for adapted endpoints soon so that all four RAs involved will have been onboard, and based on what we have known about the blinded data, at least the primary endpoint will be med with statistically significant p value, in addition to some if not all of the five secondary endpoints.
The worst scenario would be that the company cannot get positive response from FDA regarding its endpoint adaptation, and will elect (after a while the company has to move ahead without FDA's buyin)to move forward to be unblinded and announce top line data, and come up with a best way forward, including journal publication, conference, etc., and later submit BLA to FDA for approval.
What FDA can do when it receives BLA, even it is not happy, it has to review the BLA, and may convene an Adcom to evaluate the data. If the data is good enough, I don't see why adcom would not recommend to FDA to approve, and FDA has no reason to decide against its own Adcom's recommendation.
All in all, if you are seeing the forest for the tree, instead of not seeing the forest for the trees, take easy and let the process play it out.
In the meantime, make the stock price up and down into own advantage.
