After being removed from the market in the United States at the end of October, the marketing of ponatinib (Iclusig) will resume, the US Food and Drug Administration (FDA) announced today. The FDA is requiring several new safety measures to address the risk for serious cardiovascular adverse effects — the reason the drug was removed from the market.
The drug's manufacturer, ARIAD, said that the FDA has approved a revised US Prescribing Information and a Risk Evaluation and Mitigation Strategy (REMS) for ponatinib. This will allow the immediate resumption of its marketing and commercial distribution in the United States.
According to a company statement, the commercial distribution of ponatinib will resume in mid-January. Until then, patients can continue to receive it through emergency and single-patient Investigational New Drug applications. The FDA has approved 350 such applications for the drug since its removal at the end of October. Approximately 260 of these were for patients who had been receiving ponatinib and about 90 were for patients approved to receive it though these channels.
The new safety measures now limit the use of ponatinib, and the revised warnings and precautions highlight the risk for serious cardiovascular events.
The indications are now limited to 2 groups of patients: adults with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL); and adults with chronic-phase, accelerated-phase, or blast-phase chronic myeloid leukemia or Ph-positive ALL for whom no other tyrosine kinase inhibitor therapy is indicated.
The FDA has also revised the Warnings and Precautions section of the label to describe vascular occlusion events, including the observed arterial and venous thrombosis and occlusions that have occurred in at least 27% of patients treated with this drug.
Revisions have also been made to the Dosage and Administration section of the label, which now states that the optimal dose of ponatinib has not yet been determined. The recommended starting dose remains at 45 mg administered orally once daily with or without food, but additional information has been included regarding dose decreases and discontinuations.
"In less than 2 months of suspending marketing and commercial distribution of [ponatinib] in the United States, we addressed the issues raised by the FDA and now are able to market and distribute [ponatinib] again in the United States," stated Harvey J. Berger, MD, chair and chief executive officer of ARIAD, in a press release. "As we look ahead to relaunching [ponatinib] in the United States and fulfilling our postmarketing requirements, we will continue to focus on understanding the benefits and risks of [ponatinib] treatment in patients with resistant or intolerant Philadelphia-positive leukemias."
The patient Medication Guide has also been revised to include safety information consistent with the safety information in the revised drug label.
According to ARIAD, the REMS program will be initiated in the next 3 weeks, and includes letters to physicians and professional societies, a fact sheet, and information that will be communicated through professional journals and displayed at scientific meetings. These materials will all be available on ponatinib's Web site.
The manufacturer has also agreed to fulfill a series of postmarketing requirements, which will begin in 2014, to gain a better understanding of the associated cardiovascular risks and to further explore doses. This includes continued follow-up of patients from the 3 ARIAD-sponsored trials to assess long-term safety, and a randomized multiple-group trial to characterize a range of doses and to inform its safe use in patients with refractory chronic-phase chronic myeloid leukemia.
More information about today's announcement is available on the FDA Web site.
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Cite this: Ponatinib (Iclusig) Returns to Market, With a Few Caveats - Medscape - Dec 20, 2013.