Ponatinib Hydrochloride Withdrawn from U.S. Markets
Brand name(s): Iclusig
- Withdrawn from U.S. Markets
On October 31, 2013, the FDA asked the manufacturer of the leukemia chemotherapy drug ponatinib hydrochloride to suspend marketing and sales of this drug because of the risk of life-threatening blood clots and severe narrowing of blood vessels. The FDA will continue to evaluate the drug to further understand its risks and potential patient populations in which the benefits of the drug may outweigh the risks. Patients currently receiving ponatinib hydrochloride should discuss with their health care professionals the risks and benefits of continuing treatment with the drug.
The drug manufacturer, Ariad Pharmaceuticals, has agreed to FDA’s request to suspend marketing and sales of ponatinib hydrochloride while FDA continues to evaluate the safety of the drug. At this time, patients and health care professionals should follow FDA’s new recommendations for the drug:
- Patients currently taking ponatinib hydrochloride who are not responding to the drug should immediately discontinue treatment and discuss alternative treatment options with their health care professionals.
- Patients who are currently taking ponatinib hydrochloride and responding to the drug and whose health care professionals determine that the potential benefits outweigh the risks should be treated under a single-patient Investigational New Drug (IND) application or expanded access registry program while FDA’s safety investigation continues. FDA will work with the manufacturer on a plan to quickly transition these patients to a program that will allow access under an IND or expanded access registry program.
Patients: For more information on access to treatment under an IND, please refer to the following website: http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/AccesstoInvestigationalDrugs/ucm176098.htm.
- Health care professionals should not start treating new patients with ponatinib hydrochloride unless no other treatment options are available and all other available therapies have failed. Upon the determination of their health care professional, these patients can be considered for treatment under an IND or expanded access registry program.
Health care professionals: For more information on obtaining access to treatment for your patient under an IND, please refer to the following website: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/ucm107434.htm
FDA’s recent investigation of ponatinib hydrochloride revealed an increased frequency of blood clots and narrowing of blood vessels since the drug was approved in December 2012. Currently, approximately 24 percent of patients (nearly 1 out of 4) in the Phase II clinical trial (median treatment duration, 1.3 years) and approximately 48 percent of patients in the Phase I 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. In some patients, fatal and serious adverse events have occurred as early as 2 weeks after starting ponatinib hydrochloride therapy. The Phase I and II clinical trials did not include a control group, so it is not possible to determine the relationship of these adverse events to ponatinib hydrochloride; however, the increasing rate and pattern of the events strongly suggests that many are drug related. At this time, FDA cannot identify a dose level or exposure duration that is safe.
In the Phase II clinical trial, adverse events affecting the blood vessels that supply the heart were observed in 12 percent of patients; adverse events affecting the brain were observed in 6 percent of patients; and adverse events affecting the extremities were observed in 8 percent of patients. Patients with and without cardiovascular risk factors, including patients in their 20s, have experienced these events. Serious adverse reactions involving the eyes that have led to blindness or blurred vision have occurred in patients treated with ponatinib hydrochloride. High blood pressure occurred in 67 percent of patients treated with ponatinib hydrochloride in the clinical trials. Heart failure, including fatalities, occurred in 8 percent of patients treated with the drug.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.