Iclusig ponatinib regulatory update

EMA's CHMP endorsed recommendations made by the agency's Pharmacovigilance Risk Assessment Committee (PRAC) earlier this month to strengthen the warnings about blood clots and arterial blockage for Iclusig ponatinib from Ariad after a review of the risks and benefits of the leukemia drug. The PRAC noted the risk is likely dose-related, but it did not formally recommend a lower dose because of insufficient data as well as the risk that a lower dose of the drug may not be as effective in all patients and in long-term treatment. The recommended starting dose should remain 45 mg once daily, according to CHMP. Additionally, healthcare professionals should stop Iclusig if a complete response has not occurred within 3 months of treatment and should monitor patients for high blood pressure or signs of heart problems. CHMP also said a study on the safety and benefits of Iclusig is planned to clarify if lower doses carry a lower risk of blood clots or blockages of blood vessels while still having a beneficial effect. In December, EMA's CHMP started an "in-depth review" of the pan- BCR-ABL tyrosine kinase inhibitor (TKI) at the request of the European Commission (see BioCentury, Nov. 25, 2013 & Oct. 20, 2014).

Iclusig is approved in the EU to treat chronic, accelerated or blast phase chronic myelogenous leukemia (CML) in patients who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or in patients who have the T315I variant of BCR-ABL tyrosine kinase. Iclusig also is approved for Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) patients who are resistant to or intolerant of dasatinib and for whom imatinib is not appropriate, or in patients who have the T315I variant. In the U.S., Iclusig is approved for chronic, accelerated or blast phase CML and Ph+ ALL in patients who have the T315I variant of BCR-ABL tyrosine kinase or in patients for whom no other TKI therapy is indicated. Iclusig has Orphan Drug status to treat CML and Ph+ ALL in the U.S. and EU. ...