Abbvie voluntarily recalls Ibrutinib in MCL and MZL

Shine was a horrible study, as I said, so (reading btw lines) FDA would not accept it

Breaking news yesterday: Abbvie will withdraw Ibrutinib indication for MCL and MZL. This is because of SHINE and SELENE. Here is what I think happened….

FDA probably thinks that SHINE would have resulted in overall survival decrement had appropriate post protocol therapy been given. Thus, a PFS gain in the absence of OS with toxicity is untenable, especially if there are treatment related deaths that are a problem. Elsewhere I discuss why SHINE is such a poor clinical trial. Check out the video.

I think that my assessment remains spot on and is shared by the FDA.

I haven’t read SELENE but it sounds like it was stone cold negative. Wonder why they aren’t in a rush to publish it?

Here is the big issue: these studies don’t disprove ibrutinib in the salvage setting, which is the subject of the initial approvals. They only disprove it in the front line setting. Ironically however, all the eggs are in that basket in terms of the post marketing commitment. For that reason the drug is being lost in the latter lines, where it might actually make sense.

However, given that the drug enjoys other approvals, I am sure the NCCN will continue to endorse it in latter lines. NCCN does not adhere to FDA decisions, and in general expands indications.

In my book Malignant, I describe a better system of drug development. It would have worked here. Initial trials would test Ibrutinib vs standard of care in latter lines powered for OS, and then subsequent trials like SHINE would build in crossover (if latter line trials succeeded). This way we would know, when if ever, the drug helps improve OS in patients, and we would preserve a salvage indication even if front line trials lost.

Current FDA rules are invented by the people at the agency. They are not specified in law. They are statutory interpretations with wide flexibility. The FDA was once too weak, but now are wielding their power in a bizarre way. Pulling a latter line approval that still might help because front line trials failed.

What is revealed more than anything in the story of Ibrutinib in MCL is the irrational rules of FDA. Recently, after the Idelalisib fiasco, they started to agree with me about RCTs in general, soon they will agree with me about this as well.