The U.S. Food and Drug Administration (FDA) just issued an updated Drug Safety Communication asking Ariad Pharmaceuticals, the maker of the leukemia drug, Iclusig (ponatinib), to suspend its marketing and sales following increased reports of serious blood clots in arteries and veins. Iclusig received FDA approval in December 2012.
The October 31, 2013 Communication is a follow-up to its prior announcement dated October 11, 2013.
The agency indicated that it would continue to evaluate Iclusig to better understand its risks-benefit profile, and advises patients currently being treated with Iclusig to speak to their heath care professionals concerning continuing treatment. Ariad Pharmaceuticals indicated that it agreed with the agency’s request.
The FDA issued new recommendations for Iclusig:
- Patients taking Iclusig who are not responding to the drug should discuss alternative treatment options with their physicians and immediately discontinue Iclusig treatment.
- Patients taking Iclusig who are responding to treatment and whose physicians feel Iclusig’s benefits outweigh its risks, should receive treatment under a single-patient Investigational New Drug (IND) application or the expanded access registry program while the agency continues its safety investigation. The agency indicated it will collaborate with Ariad Pharmaceuticals on this transition plan.
- Health care professionals should not initiate new patient treatment for Iclusig unless there are no other available treatment options and all other treatments have failed. A health care professional should consider these patients for treatment under an IND or expanded access registry program.
The FDA’s Iclusig investigation revealed that approximately 24 percent of patients in the Phase 2 clinical trial and approximately 48 percent of patients in the Phase 1 clinical trial experienced serious adverse vascular events, including fatal and life-threatening heart attack, stroke, loss of blood flow to the extremities resulting in tissue death, and severe narrowing of blood vessels in the extremities, heart, and brain that necessitated urgent surgical procedures to restore blood flow. Some patients suffered from fatal and serious adverse events in as early as two weeks after beginning Iclusig therapy. The Phase 2 trial’s median treatment duration was 1.3 years; the Phase I was 2.7 years.
Although a control group was not involved, the increasing rate and pattern of adverse events strongly suggests that many such events are drug-related, according to the agency. The FDA indicated that it can not, currently, identify a safe dose level or exposure duration.
In the Phase 2 clinical trial, adverse events that affected those blood vessels that supply the heart, brain, and extremities were observed in 12 percent, 6 percent, and 8 percent of patients, respectively. Of note, patients with and without cardiovascular risk factors, including younger patients in their 20s, experienced these events.
Also, patients taking Iclusig suffered from significant adverse reactions involving the eyes, which led to blindness or blurred vision. High blood pressure occurred in 67 percent of patients in Iclusig clinical trials and heart failure, including with death, took place in 8 percent of patients. In some cases, according to The New York Times, loss of blood to the extremities in patients taking Iclusig, resulted in amputations.
“Those are pretty significant numbers,” Stephanie Yao, an FDA spokeswoman, told the Times. “We can’t let a drug continue to be marketed with that profile.” said Yao, who noted that Iclusig is not being permanently withdrawn.
Iclusig was approved to treat chronic myeloid leukemia, according to the Times.