FDA Requires Multiple New Safety Measures for Leukemia Drug Iclusig; Company Expected to Resume Marketing?

FDA is requiring several new safety measures for the leukemia drug Iclusig (ponatinib) to address the risk of life-threatening blood clots and severe narrowing of blood vessels. Once these new safety measures are in place, the manufacturer of Iclusig is expected to resume marketing to appropriate patients. Healthcare professionals should review these additional safety measures and carefully consider them when evaluating the risks and benefits of Iclusig for each patient.

The required safety measures involve label changes to narrow the indication, provide additional warnings and precautions about the risk of blood clots and severe narrowing of blood vessels, revise recommendations about dosage and administration of Iclusig, and update the patient Medication Guide. FDA is also requiring a risk evaluation and mitigation strategy (REMS). In addition, the manufacturer of Iclusig, ARIAD Pharmaceuticals, must conduct postmarket investigations to further characterise the drug’s safety and dosing.

On 31 October 2013, FDA requested and ARIAD agreed to voluntarily suspend marketing of Iclusig. FDA’s request resulted from FDA’s investigation, which revealed a steady increase in the number of serious vascular occlusion events identified through continued safety monitoring of the drug. This observation represented a significant change in the safety profile of Iclusig as the proportion of patients on the drug experiencing vascular occlusion events such as blood clots and severe narrowing of blood vessels was significantly greater than the proportion reported at the time of its approval in December 2012.

During the marketing suspension, Iclusig treatment has been available through single patient or emergency investigational new drug applications (INDs). Patients should continue to receive Iclusig under their authorised IND until marketing of Iclusig is resumed. FDA is working closely with ARIAD on the new safety measures and anticipates these will be in place by the end of January 2014. Once that process is complete, patients being treated under these INDs can be transitioned back to receiving the marketed Iclusig product.