Ariad Pharmaceutics said today it will end its Phase III EPIC or “Evaluation of Ponatinib vs. Imatinib in Chronic Myeloid Leukemia” trial of Iclusig (ponatinib) for patients with newly diagnosed CML.
The company said it and the FDA “mutually agreed that the trial should be terminated” after patients treated with Iclusig experienced increased blood clotting. The decision came a week after the FDA placed a partial clinical hold on the trial, following which Ariad halted enrollment of new patients, reduced the dosage of Iclusig to patients in the trial’s drug arm to 30 mg from 45 mg, and changed the trial’s patient eligibility criteria to exclude patients with prior arterial thrombosis resulting in heart attack or stroke.
Ariad also publicly discussed the possibility of a change to its U.S. prescribing label in an October 9 announcement that disclosed an 11.8% rate of serious arterial thrombosis in Iculsig-treated patients after 24 months of treatment, vs. the 8% rate after 12 months disclosed on its prescribing label.
“Our decision to stop the EPIC trial at this time is based on our current evaluation of the safety data in the trial since it was placed on partial clinical hold last week,” Timothy P. Clackson, Ph.D., Ariad’s president of R&D and cso, said today in a statement. "We believe that this is in the best interests of patient safety and the overall development of Iclusig.”
Ariad said a total 307 patients were enrolled in EPIC, a randomized, two-arm, multicenter trial designed to compare the efficacy of ponatinib and imatinib in adults with newly diagnosed chronic CML. The trial was being conducted at about 150 investigational sites in more than 20 countries. Patients had to be at least 18 years of age and CML-diagnosed within six months before enrollment.
Based on Phase II data, Iclusig won FDA accelerated approval for resistant or intolerant CML and Philadelphia-chromosome positive acute lymphoblastic leukemia patients. in December 2012. Ariad began marketing the $115,000-a-year drug, while continuing clinical trials designed to add indications allowing wider use of the drug.
“Ariad continues to work with health authorities to make appropriate changes to the Iclusig product labeling to reflect the recently announced safety findings from the pivotal PACE trial that was the basis of its marketing approvals,” the company said.
Ariad was one of seven companies GEN recently declared as “Takeover Targets” based on rosy sales projections for Iclusig tied to the expectation of new indications. The drug had been projected by Cowen & Co. to reach $625 million in 2017 and more than $1 billion ultimately in annual sales; it generated $20.3 million in the first half of 2013.