The U.S. Food and Drug Administration (FDA) has asked ARIAD Pharmaceuticals, the manufacturer of Iclusig (ponatinib) to suspend marketing and sales of ponatinib because of the risk of life-threatening blood clots and severe narrowing of blood vessels. FDA asks ARIAD to suspend marketing and sales of Iclusig (ponatinib) In a press release, the FDA said that it is continuing to evaluate the drug to further understand its risks and potential patient populations in which the benefits of the drug may outweigh the risks.

Iclusig is used for the treatment of patients with advanced chronic myeloid leukemia that is resistant to other drugs. It is also being tested in a phase II clinical trial for advanced GIST patients that have failed other therapies.

According to Dr. Suzanne George, one of the principal investigators of the GIST trial at Dana Farber Cancer Center, “We have been informed by ARIAD that they continue to work closely with the FDA. We are working to stay in close communication with ARIAD as new information becomes available. The trial remains closed to new participants. For those patients who remain on ponatinib within the context of the ongoing GIST trial, continued communication between patient and provider to assess risk/benefit remains important. We will continue to ensure protocol participants at our site are informed as we learn new information.”

Dr. Michael Heinrich of the Knight Cancer Institute in Oregon, a co-investigator in the GIST trial, added further comments about the trial, “We are being continually updated on new risk information/advice.  For now, existing patients on the study can continue treatment as prescribed.  We are awaiting further information on when or if the study will re-open to enrollment and whether changes in dosing or patient eligibility will be indicated.”

The risks detailed by the FDA are a serious concern. The question that remains is whether there might still be some patient group that might benefit. Dr. Margaret von Mehren, another co-investigator in the GIST trial from Fox Chase Cancer Center, commented about the GIST patients in the phase II trial, “Ongoing communication with patients is clearly important and continuing to weigh the risk versus benefit for each individual patient.”

Here is what Jerry Call, the LRG Science Director:

The recent  news of cardiovascular risks with ponatinib are a big concern. Ponatinib is approved for use in advanced CML and in trials for use in advanced GIST. CML and GIST different in one important aspect. Patients with CML, as a group, do better than GIST patients. This is especially true for patients that fail imatinib, which is the first line therapy in both diseases. In CML, the drugs given to rescue patients that fail imatinib are very effective. Both Tasigna and Sprycel produce excellent results in advanced CML. However, the drugs for advanced GIST patients are significantly less effective. A large percentage of GIST patients will eventually fail Gleevec, Sutent and Stivarga and potentially need another therapy. In CML, a smaller percentage will need that drug of last resort. It’s possible that the risk to benefit ratio will still favor giving to ponatinib to some patients and that more GIST patients will need that drug of last resort than CML patients.


The European Medicines Agency’s Committee for Medicinal Products for Human Use(CHMP) is recommending a change in use of Iclusig (Ponatinib) to help minimize the risk of blood clots obstructing arteries or veins in patients. For more details, read the full article here.


Further reading

FDA press release

ARIAD press release