Leukemia drug Iclusig (ponatinib) is the focus of a U.S. Food and Drug Administration (FDA) Drug Safety Alert over its association with serious blood clots. Ariad Pharmaceuticals, Inc. manufactures Iclusig.
The FDA has asked Ariad Pharmaceuticals to cease marketing of the dangerous drug Iclusig after receiving reports of serious blood clots in patients' veins and arteries. The drug received FDA clearance in December 2011 and is used in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ariad describes Iclusig as a kinase inhibitor that targets BCR-ABL, an abnormal tyrosine kinase. In other words, Ariad interrupts the enzymes in cancer cells that cause cancer to multiply. Iclusig is delivered in either 15 mg or 45 mg oral tablets.
In its current safety announcement, dated October 31, 2013, the agency indicated that it would evaluate Iclusig and its risk-benefit profile, and stated that patients treated with Iclusig should discuss treatment with their health care professionals. The new safety announcement is an update to the agency's prior update dated October 11, 2013.
The FDA indicates that Iclusig patients who are not responding to treatment should discuss alternative treatments with their physicians and their Iclusig treatment should be stopped. In patients who are responding to Iclusig and whose doctors feel the drug's risks are outweighed by its benefits, patients should receive that treatment using a single-patient Investigational New Drug (IND) application or the expanded access registry program. The FDA indicated that it would work with Ariad on this plan. The agency also stated that health care professions should not begin new patient treatment for Iclusig unless all other treatment options have failed and, if new Iclusig treatment is considered, and IND or expanded access registry program should be used.
The agency's Iclusig probe revealed that about 24 percent of patients enrolled in Phase 2 clinical trial experienced significant adverse vascular events; 48 percent of the patients in the Phase I clinical trial also experienced similar side effects. Side effects were seen in as soon as two weeks following treatment with Iclusig and included fatal and life-threatening heart attack; stroke; blood flow loss to limbs that resulted in tissue death and amputations; and severe blood vessel narrowing in the extremities, heart, and brain, which required immediate surgery to restore the flow of blood. Patients with no cardiovascular risk factors, including patients in their 20s, experienced these adverse side effects when taking Iclusig.
Patients also suffered from significant adverse optical reactions, which led to blindness or blurred vision and high blood pressure. Initial drug trials also revealed that Iclusig could lead to blood clots (thrombosis) and hepatoxicity (liver toxicity), which led to a black box warning on Iclusig's label when it was approved. Other adverse reactions include pancreatitis, hemorrhage, and water retention.
Iclusig was approved under an accelerated process; therefore Ariad was mandated to conduct additional drug trials following approval. The FDA warned that Iclusig could lead to an array of adverse reactions based on these results and adverse report events.
Ariad announced that it ceased critical trial enrollment for Iclusig, that dosing for Iclusig would be reduced from 45 mg, and that future clinical trials will exclude patients diagnosed with a history of arterial thrombosis.
- The U.S. Food and Drug Administration: http://www.fda.gov/Drugs/DrugSafety/ucm373040.htm
- Ariad Pharmaceuticals, Inc.: ARIAD Announces Temporary Suspension of Iclusig Marketing in the United States