At the request of the US Food and Drug Administration (FDA), the leukemia drug ponatinib (Iclusig) has been temporarily pulled from the market by its manufacturer, Ariad Pharmaceuticals, because of safety concerns.
“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,” said the FDA in a statement.
The company will suspend marketing and sales of ponatinib because of the risk for life-threatening blood clots and severe narrowing of blood vessels.
Ponatinib is indicated for adults with chronic-phase, accelerated-phase, or blast-phase chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia who do not tolerate or no longer benefit from other therapies, such as imatinib (Gleevec, Novartis).
This action follows an FDA investigation into ponatinib, initiated earlier this month, that revealed “an increased frequency of blood clots and narrowing of blood vessels since the drug was approved in December 2012,” according to an agency statement.
New data indicate that approximately 24% of patients in the phase 2 clinical trial (median treatment duration, 1.3 years) and approximately 48% of patients in the phase 1 clinical trial (median treatment duration, 2.7 years) experienced serious adverse vascular events. The events include 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 the phase 2 trial, heart failure, including fatalities, occurred in 8% of patients treated with the drug. Serious adverse reactions involving the eyes, which led to blindness or blurred vision, also occurred.
In some patients, fatal and serious adverse events have occurred as early as 2 weeks after starting ponatinib therapy.
Currently, the FDA cannot identify a dose level or exposure duration that is safe.
Patients on ponatinib who are not responding should stop treatment and seek an alternative, according to the FDA.
For patients who are responding to ponatinib and whose healthcare professionals determine that the potential benefits outweigh the risks, the agency recommends that they continue to be treated under a single-patient Investigational New Drug (IND) application or under an expanded-access registry program while FDA investigation continues.
More information on obtaining access to treatment under an IND can be found on the FDA Web site.
Clinicians should not start treating new patients with ponatinib unless no other treatments are available and all other available therapies have failed, according to the FDA.
When the FDA approved ponatinib 10 months ago, it required the label to feature a boxed warning about the risk for blood clots. Clinical trials conducted prior to approval reported serious arterial blood clots in 8% of patients treated with the drug, and venous blood clots in 3%.