EMA Changes Ponatinib Recommendations, Leaves Drug on Market

December 4, 2013

Following recent trial data showing an increased risk of dangerous blood clots with ponatinib, which led the FDA to request that the manufacturer stop marketing the drug, the FDA’s European counterpart has adjusted its recommendations for ponatinib but has not changed its “positive opinion” that led to the approval.

Following the US Food and Drug Administration’s request that the manufacturer stop marketing the cancer drug ponatinib (Iclusig), the FDA’s European counterpart has adjusted its recommendations regarding ponatinib but has not changed its “positive opinion” that led to the drug’s approval. Recent trial data has shown an increased risk of dangerous blood clots with ponatinib.

The company, Ariad Pharmaceuticals, based in Cambridge, Massachusetts, highlighted the European Medicines Agency’s Committee for Human Medicinal Products’ (CHMP) decision not to pull the drug, but the CHMP did recommend some important changes to how ponatinib is used. It is still recommended for use in adult patients with chronic myeloid leukemia (CML) in the chronic, accelerated, or blast phases, if patients have proven intolerant or resistant to other tyrosine kinase inhibitors including imatinib and nilotinib; it is also indicated for use in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

The new recommendations, however, include avoiding the use of ponatinib in patients who have had a heart attack or stroke in the past, “unless the potential benefits to them outweigh the risks.” The committee also recommends that the cardiovascular risks to all patients are assessed, and any appropriate measures to reduce risk should be taken before treatment initiation. Patients with high blood pressure should have it controlled in order to take ponatinib, and any sign of either vascular occlusion or thromboembolism should lead to an immediate cessation of the drug.

“We have been working closely with the EMA to provide updated clinical-trial data on patients treated with Iclusig,” said Jonathan E. Dickinson, Ariad Europe’s general manager, in a press release. “The conclusions reached by the CHMP… confirm a positive benefit-risk assessment for Iclusig after considering the most recent safety information. We expect that this will provide helpful guidance for patients and healthcare professionals as they consider the treatment options.”

The FDA first issued a safety advisory on the risks associated with ponatinib in early October, and later in the month requested that ARIAD stop marketing the drug in the United States. The agency cited phase I and II trial results; in the latter, 24% of patients experienced some serious vascular event. In the phase I trial, after 2.7 years of treatment almost half of the patients (48%) have experienced related adverse events.

The EMA noted results from another trial, a phase III study comparing ponatinib and imatinib that has been discontinued. According to the EMA news release, though data are still preliminary, the larger phase III trial also shows evidence that occlusive vascular events are more common with ponatinib. The drug was initially approved in the United States in December 2012 and in the European Union in July 2013.