FDA Drug Safety Podcast: FDA requires multiple new safety measures for leukemia drug Iclusig; company expected to resume marketing

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Welcome to the FDA Drug Safety Podcast for Healthcare Professionals from the Division of Drug Information. Today’s topic: FDA requires multiple new safety measures for leukemia drug Iclusig; company is expected to resume marketing.

On December 20th, 2013, the FDA issued a drug safety communication informing the public that the Agency is requiring several new safety measures for the leukemia drug Iclusig (active ingredient 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. Health care 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. We are also requiring a risk evaluation and mitigation strategy (or REMS). In addition, the manufacturer of Iclusig, ARIAD Pharmaceuticals, must conduct postmarket investigations to further characterize the drug’s safety and dosing. This includes further evaluation of dose selection, drug exposure, treatment response, and toxicity of Iclusig therapy.

On October 31, 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 of 2012.

During the marketing suspension, Iclusig treatment has been available through single patient or emergency investigational new drug applications (or INDs). Patients should continue to receive Iclusig under their authorized 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.

At this time FDA recommends that healthcare professionals be aware of the following:

  • The Warnings and Precautions in the label are revised to describe the vascular occlusion events. This includes a description of the observed arterial and venous thrombosis and occlusions that have occurred in at least 27% of patients treated with Iclusig from phase 1 and 2 trials. These adverse events have included fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures.
  • Iclusig can cause fatal and life-threatening vascular occlusions within 2 weeks of starting treatment. Iclusig can also cause recurrent or multi-site vascular occlusions.
  • Inform patients about the signs and symptoms of vascular occlusion events and advise them to seek immediate medical treatment if they experience symptoms suggesting a heart attack (such as chest pain or pressure; pain in their arms, back, neck or jaw; or shortness of breath), or symptoms of a stroke (such as numbness or weakness on one side of the body, trouble talking, severe headache, or dizziness).
  • The optimal dose of Iclusig has not been identified. The recommended starting dose remains 45 mg administered orally once daily with or without food; however, additional information is included regarding dose decreases and discontinuations
  • We expect that a REMS letter to healthcare professionals will be sent electronically or by mail to hematologists, oncologists, and other health care professionals known or likely to prescribe Iclusig by the end of January 2014. Prescribing Information and the Iclusig REMS fact sheet will accompany the letter.
  • The Iclusig REMS Web site will contain information on the Iclusig REMS and will provide access to all the REMS materials and the U.S. Prescribing Information.   The site should be available soon and for the duration of the REMS.
  • Health care professionals should continue to work closely with FDA and ARIAD for patients currently receiving Iclusig under single patient or emergency INDs until the resumed marketing of Iclusig is complete as anticipated in January 2014 and the drug is available without an IND.
  • ARIAD will send letters to all IND holders with an estimated time for transitioning these INDs to commercial supply. The company will send a second communication at the time full commercial distribution resumes. Specialty pharmacies will provide outreach to IND holders at the time of full marketing resumption to help facilitate this transition. Please refer to www.iclusig.com for further information.
  • Encourage patients to read the patient Medication Guide for Iclusig.
  • Adverse events involving Iclusig should be reported to the FDA MedWatch program at www.fda.gov/medwatch.

Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. A link to this communication detailing the specific Iclusig REMS components, the newly limited indications, and complete Data Summary can be found at www.fda.gov/DrugSafetyCommunications. If you have drug questions, you can reach us at druginfo@fda.hhs.gov.

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