[11-5-2013] This information is a follow up to the FDA Drug Safety Communication: FDA asks manufacturer of the leukemia drug Iclusig (ponatinib) to suspend marketing and sales issued on October 31, 2013.
The U.S. Food and Drug Administration (FDA) is providing instructions to health care professionals whose patients have been taking Iclusig (ponatinib) and are benefiting from the drug, on how to continue those patients on the drug. We are working closely with Iclusig's manufacturer, ARIAD Pharmaceuticals (ARIAD), to avoid interruptions in treatment. At this time, Iclusig treatment may be continued for appropriate patients under an emergency Investigational New Drug (IND) application.
Health care professionals (HCPs) may continue to use Iclusig for patients who they determine are responding to the drug and for whom the potential benefits outweigh the risks. As stated previously, HCPs should immediately discontinue Iclusig treatment for patients who are not responding to the drug and discuss alternative treatment options with them. New patients should not be started on Iclusig unless no other treatment options are available and all other available therapies have failed.
How Health Care Professionals Can Obtain Emergency Access to Iclusig:
Step 1: You, the health care professional, should contact FDA to receive an emergency IND number:
- 301-796-7550 between 8:00 a.m. and 4:30 p.m. EST Monday through Friday
- 866-300-4374 or 301-796-8240 after 4:30 p.m. EST
Please have the following information when calling FDA:
- Patient initials and date of birth
- Your name and contact information (address, phone number, and email address)
- Indication for treatment and dosing regimen
If you have multiple patients who will need Iclusig, you may request multiple INDs during a single telephone call to FDA. We will provide the corresponding amount of IND numbers at the end of the call. You should anticipate when the drug supply would be needed and initiate the emergency IND process as early as possible. Contact FDA at least 48-72 hours in advance of the anticipated drug need.
Step 2: Contact ARIAD at 855-552-7423 and provide the IND number and address for shipping. ARIAD will send a shipment request form and informed consent document to you. After ARIAD receives the signed shipment request form back from you, ARIAD will have the drug shipped by courier to your office.
Step 3: ARIAD also will provide a packet that you will be required to submit to the FDA within 15 working days of your emergency IND request being granted.
We believe the steps above will ensure an uninterrupted supply of Iclusig to patients currently taking the drug. Please check this site for updates as we continue to review the safety of this drug and determine next steps.
This update is in follow-up to the FDA Drug Safety Communication: FDA investigating leukemia drug Iclusig (ponatinib) after increased reports of serious blood clots in arteries and veins issued on October 11, 2013.
Safety Announcement
[10-31-2013] The U.S. Food and Drug Administration (FDA) has asked the manufacturer of the leukemia chemotherapy drug Iclusig (ponatinib) to suspend marketing and sales of Iclusig because of the risk of life-threatening blood clots and severe narrowing of blood vessels. We 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 Iclusig 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 Iclusig while we continue 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 Iclusig 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 Iclusig 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: Access to Investigational Drugs Outside of a Clinical Trial (Expanded Access).
- Health care professionals should not start treating new patients with Iclusig 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: Physician Request for an Individual Patient IND under Expanded Access for Non-emergency or Emergency Use
FDA's recent investigation of Iclusig 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 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. In some patients, fatal and serious adverse events have occurred as early as 2 weeks after starting Iclusig therapy. The Phase 1 and 2 clinical trials did not include a control group so it is not possible to determine the relationship of these adverse events to Iclusig, 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 2 clinical trial, adverse events affecting the blood vessels that supply the heart, brain, and extremities were observed in 12 percent, 6 percent, and 8 percent of patients, respectively. Patients with and without cardiovascular risk factors, including patients in their 20s, have experienced these events. Serious adverse reactions involving the eyes, which led to blindness or blurred vision, occurred in Iclusig-treated patients. High blood pressure occurred in 67 percent of patients treated with Iclusig in the clinical trials. Heart failure, including fatalities, occurred in 8 percent of patients treated with the drug.
We will continue to notify health care professionals and patients in a timely manner as more information becomes available.a