EU CHMP Completes Review of Ponatinib, Finalizes Warnings

The Committee for Medicinal Products for Human Use (CHMP) in Europe has now completed its review of ponatinib (Iclusig, ARIAD Pharmaceuticals, Inc), and has recommended stronger warnings for the product.

Ponatinib is a tyrosine-kinase inhibitor approved for use in patients with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) who cannot take or tolerate other tyrosine- kinase inhibitors.

CHMP's review of the benefits and risks of ponatinib was prompted by concern over cardiovascular side effects. Clinical trial data had revealed that cases of blood clots and blockages in the arteries or veins were occurring at a higher rate than was observed at the time of the medicine's initial authorization, the committee explained.

The CHMP now says that the available evidence shows that the risk for serious cardiovascular events is likely to be dose-related, but the data are currently insufficient to formally recommend using lower doses. There is also a risk that lower doses might not be as effective in all patients and in long-term treatment.

Thus, the committee recommends that the starting dose remain 45 mg once a day, and product information will be updated with strengthened warnings about the associated risks.

In the United States, ponatinib returned to the market last December, after being temporarily pulled by its manufacturer because of the same safety concerns. The US Food and Drug Administration (FDA) has required several new safety measures to address these serious drug-related risks.

"We are now well positioned to complete pricing and reimbursement negotiations in Europe and to ensure that Iclusig is available to appropriate Philadelphia chromosome–positive leukemia patients," said Jonathan E. Dickinson, general manager, ARIAD Pharmaceuticals (Europe), in a release. "The authorized indications and the favorable benefit-risk balance of Iclusig give healthcare providers the ability to optimize the use of Iclusig in patients with resistant or intolerant CML."

The review of ponatinib was initially carried out by the EMA's Pharmacovigilance Risk Assessment Committee, and a planned study on the safety and benefits of the drug is intended to help clarify whether lower doses would reduce the risk for blood clots while still providing benefit to patients with chronic-phase CML.

Although the recommendations are not binding, the European Commission generally follows the recommendations of the CHMP and delivers its final decision around 2 months after the CHMP recommendations.

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Cite this: EU CHMP Completes Review of Ponatinib, Finalizes Warnings - Medscape - Oct 24, 2014.

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