On October 31, 2013, the FDA announced that Ariad Pharmaceuticals has agreed to suspend marketing and sales of the leukemia drug Iclusig (ponatinib) due to the risk of life-threatening blood clots and severe narrowing of blood vessels. Earlier this month, ARIAD Pharmaceuticals announced that the FDA had placed a clinical hold on all new patient enrollment in clinical trials of Iclusig after new study data raised concerns about the drug’s safety.
Iclusig is a kinase inhibitor used for the treatment of adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases. The drug was approved last December with a black box warning alerting patients and health care professionals that the drug can cause blood clots and liver toxicity.
The FDA’s investigation of Iclusig revealed an increased frequency of blood clots and narrowing of blood vessels since the drug was approved. In a Drug Safety Communication, the agency stated:
Currently, approximately 24 percent of patients (nearly 1 out of 4) in the Phase 2 clinical trial (median treatment duration 1.3 years) and approximately 48 percent of patients in the Phase 1 clinical trial (median treatment duration 2.7 years) have 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 requiring urgent surgical procedures to restore blood flow.
The FDA stated that they will continue to evaluate Iclusig to understand the risks and potential patient populations in which the benefits of the drug may outweigh the risks.
Iclusig (ponatinib) belongs to a class of drugs known as kinase inhibitors. Using FAERS data (from 11/01/1997 to 12/31/2012), aggregated and standardized by the AdverseEvent RxFilter process, we analyzed the reported venothrombotic and cardiovascular adverse events associated with kinase inhibitors (Gleevec, Sprycel, Tarceva, Tykerb, Jakafi, Nexavar, Sutent, Votrient, Xalkori, Tasigna, Afinitor, Torisel, Caprelsa, Zelboraf, Inlyta, Stivarga, Cometriq, Bosulif, Gilotrif).
We identified 339 cases involving stenosis or narrowing of blood vessels which listed a kinase inhibitor as the primary suspect drug. There were 2,433 total cases involving venothrombotic adverse events which listed a kinase inhibitor as the primary suspect drug. The top venothrombotic adverse events were pulmonary embolisms (blockages of the main artery of the lung) and deep vein thromboses (deep vein blood clots). The three kinase inhibitors with the most cases involving venothrombotic adverse events were Tarceva (500 cases), Sutent (427 cases), and Nexavar (409 cases).
There were 1,533 reported patient hospitalizations and 719 patient deaths involving venothrombotic adverse events which listed a kinase inhibitor as the primary suspect drug.
Note: This analysis does not take into account the number of patients taking each medication. In order to calculate the total number of cases involving venothrombotic adverse events, we aggregated reports listing the following adverse events: MedDRA High-Level Group Term: Embolism and thrombosis.