Het volgende is de grote valkuil en iets wat ik niet begrijp:
Can somebody please explain to me, on what scientific ground can Fazirsiran possibly reverse fibrosis? Is it all false hope, and, those 38% or 50% improvement are just fluctuations in the liver sample? Maybe, attempting to reversing fibrosis has been a waste of time. The program should have been focused on toxicity and knockdown of bio markers. Some years ago CA gave me the impression that reversing reversing fibrosis was not a requirement.
If not required, then why add on to (significantly) increase the complexity of the trial. For expanded claims and label? The add-on can come later.
Without the fibrosis reversing claim, just based on bio markers, we have a clear-cut case.
When I Googled “examples of liver fibrosis reversal” a 2015 paper in Clinic Research Hepatology Gastroenterol popped up. The Abstract says: until now, there is no effective therapy available for liver fibrosis except the removal of underlying etiology or liver transplantation”
Any new development since 2015? Or, are all the involved parties, from Arrowhead to the FDA, stupid enough to place a heavy weight on fibrosis reversal so as to delay the treatment for the poor patients?
Of zoals iemand anders het stelt:
Do I understand this correctly? FDA has determined that fibrosis reduction is now a decided criteria for TAK-999 siRNA success as a drug, and by extension should it be now assumed that same criteria will be required of all other AAT drug therapy submissions to FDA regardless of the modality? Is that truly what Takeda, and probably to a lesser extent ARWR (since ARWR isn't paying for the P3 study) just agreed upon with FDA? If so, did Takeda and ARWR just throw a bunch of wrenches in the gearing of the rest of those pharma co's pursuing a therapy? And if so, the competition has to be running around in circles with their underwear pulled over their heads about right now.
Maar:
If it is the FDA that is setting fibrosis reversal as the criteria, then the FDA is intentionally or unintentionally making it more difficult for the patients to get much needed help. If it is Arrowhead or TAK that is moving the goal post, then they are just absolutely stupid. I now have real doubt that fibrosis reversal is at all possible.
Wat denk jij hiervan, Tom?