in 2013 FDA attributed ALL CV AEs to ponatinib. None caused by: Many years as a CML patient or many years taking TKIs; none caused by exposure to nilotinib; none caused by age, weight, smoking, diabetes, predisposition to clotting,coronary disease, other thrombogenic medications, etc, etc.
Even terminally ill patients in Blast Phase CML, with only days or weeks to live - if they had a CV event only a few days after starting ponatinib - FDA attributed that also to the drug, something none of the clinical investigators would have done.
Now that there is a head to head trail of ponatinib vs nilotinib, it may very well show that ponatinib is no more toxic than the second-line nilotinib. If that's the case will FDA pull nilotinib off of the market demanding a Black Box warning for CV risks? Will FDA re-analyze ALL of the clinical and post-market safety data for nilotinib with the assumption that ALL CV thrombosis events were drug related?
Key point: The safety data for ponatinib CV thrombosis events was re-analyzed by FDA differently than that for the other TKI. Usually in a clinical study, CV events are documented and categorized by the clinical investigators, who overall felt that most of these CV events were due to non-ponatinib related conditions.
Even if the data does indicate higher CV events with ponatinib, the post-withdrawal data for ponatinib is probably continuing to be analyzed as if all of the CV events are drug-related. That is one of the major problems with running a clinical trial without a placebo or comparator drug. For life-threatening diseases, placebos are not ethical and using a comparator is often too expensive for a smaller company.
Lessons learned, but still, I'd like to see a re-analysis of the CV data for ALL of the marketed TKI using this special "ponatinib-only" approach. THat woudl be the medically sound thing to do.
