IMO, the FDA made a huge mistake and I am not sure what their action will be going forwards. I do not know if they have the courage to admit they were wrong and act accordingly.
At this point with sales expected to be < 200MM annually (less than expenses leading to a loss), Biogen might just agree to take the drug off the market if a mutual face-saving statement for the FDA and Biogen could be found and approval is granted if an additional study is positive. This could then shut down the accelerated pathway approval based on one positive study and amyloid PET biomarker for other companies too. (BTD is not controversial for the other drugs as AD is important - BTD saves time and expense but still usually relies on 2 trials and does not rely on biomarkers)
If it came up for a vote, I think Ad Board consensus would have been that Biogen should run a third study as the stop and start aspects of their 2 trials led to unreliable statistics and the benefits were not stellar in the one positive study (and second study failed). The Advisory board was never told to consider accelerated approval but implied they would have voted against that as well (hence the 3 people quitting the board).
Now the FDA is stuck giving BTD to every other company that has amyloid PET data (i.e. Roche, Lilly, likely Biogen again for BAN) and judge the drug on only one controlled study with positive PET. How will they look at Anavex and SAVA, CRTX, SNPX, etc? Will they double down and accept other unproven biomarkers of efficacy (S1R mRNA, SavaDx, CSF markers, etc)? If so, then this might be good for small AD companies who will apply with thin data and gain approvals. Or, trying to avoid other controversial approvals, will the FDA become more strict for non-PET Amyloid biomarkers and expect 2 large studies like they have for years?
