UPDATE: Last night (Monday, March 14), the FDA issued a statement about Idelalisib; the manufacturer is shutting down 6 clinical trials involving patients with SLL, CLL, and indolent NHL. There statement is here (and available on their website):
The U.S. Food and Drug Administration is alerting health care professionals about reports of an increased rate of adverse events, including deaths, in clinical trials with the cancer medicine Zydelig (idelalisib) in combination with other cancer medicines.
Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary.
Health care professionals should be aware that Zydelig is not approved for previously untreated chronic lymphocytic leukemia.
Zydelig is currently approved by the FDA for the treatment of:
- Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
- Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.
- Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.
I'm still very curious to see what is happening here.
Clearly, the data presented enough of a problem to cause concern in both the U.S. and Europe, so something is up. The challenge, I guess, will be to determine what factor is the cause of the problem: the particular combination of treatments; the way the trials were designed, etc.
Here's my fear: Idelalisib was approved as a "breakthrough therapy" by the FDA, meaning its approval was based on preliminary trial results -- sooner than most treatments are approved. Would the problems have been see if the Idelalisib went through a full, traditional review? Maybe. But preliminary results have to be followed up by more trials to confirm, so the Breakthrough designation doesn't mean that they get a free pass. It just mans that they get an earlier pass.
My fear, though, is that this will call into question the value of the Breakthrough designation program, which is designed to get treatments to patients sooner than they might have. That's a good thing.
But serious Adverse Effects are not good.
There are other PI3K inhibitors in trials now, too. It will be interesting to see if they get put under closer scrutiny, or if they can show that they are not dealing with the same Adverse Effects.
I'll be keeping a close eye on this situation. It could be a while before anything happens.