Credit: CDC
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted its final opinion on ponatinib (Iclusig), saying the drug’s benefits outweigh its risks.
The CHMP recommends that ponatinib continue to be used in accordance with its approved indications.
However, the drug’s product information should be updated with strengthened warnings, particularly about the risk of arterial and venous thrombotic events.
Ponatinib is approved in the European Union (EU) to treat adults with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) 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 who have the T315I mutation.
The drug is also approved to treat adults with Philadelphia-chromosome positive acute lymphoblastic leukemia who are resistant to dasatinib, who cannot tolerate dasatinib and subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
Roughly a year ago, follow-up data revealed that ponatinib-treated patients had a higher incidence of arterial and venous thrombotic events than was observed when the drug first gained approval. So one ponatinib trial was discontinued, and the rest were placed on partial clinical hold.
Then, ponatinib was pulled from the US market. The drug ultimately returned to the marketplace with new recommendations designed to decrease the risk of thrombotic events. The EMA also revised its recommendations for ponatinib but kept the drug on the market.
PRAC review and recommendations
Because of these risks, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) conducted an 11-month review of the available data on ponatinib and consulted with a scientific advisory group.
The PRAC assessed the available data on the nature, frequency, and severity of arterial and venous thrombotic events. And the committee concluded that the benefits of ponatinib outweigh its risks.
The PRAC said the risk of thrombotic events is likely dose-related, but there are insufficient data to formally recommend using lower doses of ponatinib. And there is a risk that lower doses might not be as effective in all patients and in long-term treatment.
The PRAC therefore concluded that the recommended starting dose of ponatinib should remain 45 mg once a day.
However, the committee also recommended updates to the product information to provide healthcare professionals with the latest evidence, in case they want to consider reducing the dose in patients with chronic phase CML who are responding well to treatment and who might be at particular risk of thrombotic events.
In addition, PRAC recommended that healthcare professionals stop ponatinib if there has been no response after 3 months of treatment and monitor patients for high blood pressure or signs of heart problems.
The CHMP concurred with these recommendations and is forwarding them to the European Commission. The commission is expected to issue a final, legally binding decision on ponatinib in December 2014, which will be valid throughout the EU.
A new study on the safety and benefits of ponatinib is in the works to help clarify if lower doses of the drug carry a lower risk of thrombotic events while still having a beneficial effect in patients with chronic phase CML.
