A funny thing happened when the Europeans evaluated the same trial data that led to the approval of idelalisib in the US. They saw things differently....
Doctors and patients alike are quite interested in knowing the "package insert" for a medication. Essentially it contains the prescribing information on how to use the drug and for what conditions it is approved. This is enormously important because it often determines when an insurance company will have to pay for it to be used.
The US FDA and the European Commission on Medicinal Products look at new drugs independently. They look at all the safety of all the clinical trials and the efficacy and come to their own conclusions about when such a drug could / should be used.
The FDA took a very conservative view of the trial data and highlighted the risks and gave a fairly narrowly defined set of circumstances where the drug can be used.
In the US - the FDA has stated that it can be used in patients with CLL:
1) in combination with rituximab in patients who are not suitable for chemotherapy on account of other medical problems.
In Europe - idelalisib has been recommended for approval:
1) in combination with rituximab in patients who have had one prior line of therapy (sounds very similar to the information for ibrutinib)
2) in front line treatment for patients with 17P deletion or TP53 mutation.
2a) The best way to test for TP53 mutation linked here
2b) See my link for the new molecular markers
2c) There is a clinical trial in US utilizing idela/rtx in this same population that can be accessed through our network at these locations
The labeled indications for follicular lymphoma following two prior lines of therapy is quite similar.
The other key differences were regarding the safety of the drug. The US prescribing information highlights the risks of a variety of side effects. Things that happened to 1-2 patients (and may have due to entirely other medications) out of the 1000 treated prior to approval were listed as "black box" warnings. It appears that several of those will be stripped entirely from the European guidelines - will try to update link when it becomes available.
"package inserts" can be "living documents." They get updated as new clinical trials are released. For instance, the role for ibrutinib in patients with 17P was recently updated in the US. I expect that the package insert for both of these agents will continue to expand over time. I think the additional insight provided by our European colleagues shed new perspective on how and where we might think to use the drugs here in the US.
Thanks for reading.
