ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that it has concluded consultations with U.S. and European health authorities regarding the design of a randomized, dose-ranging trial to evaluate three starting doses of Iclusig ® (ponatinib) in patients with refractory, chronic-phase chronic myeloid leukemia (CP-CML). The trial is expected to inform the optimal use of Iclusig in these patients and will begin by mid-2015. Approximately 450 patients will be enrolled at clinical sites around the world. "This clinical trial is expected to provide important data regarding the efficacy of Iclusig treatment initiating at doses less than the currently approved starting dose and maintaining patients on a lower dose. We expect that this will better characterize the safety profile of Iclusig beginning at lower doses," said Frank G. Haluska, M.D., Ph.D., senior vice president of clinical research and development and chief medical officer at ARIAD. "We also anticipate that this trial will give us the opportunity to further explore strategies for dose reductions after patients have achieved a major cytogenetic response in order to maximize an individual's benefit/risk while on therapy." Major Design Features of the Trial This study will enroll patients with CP-CML who are resistant to at least two approved tyrosine kinase inhibitors. These patients will be randomized equally to receive once-daily administration of 45 mg (cohort A), 30 mg (cohort B) or 15 mg (cohort C) of Iclusig. Patients in cohorts A and B will have their daily dose reduced to 15 mg upon achievement of major cytogenetic response (MCyR). The primary endpoint of the trial is MCyR by 12 months for each cohort. Secondary endpoints include rate of vascular occlusive events in each dose cohort, rates of adverse events and rates of serious adverse events. Other secondary endpoints include cytogenetic, molecular and hematologic response rates, tolerability, duration of response, time to response, disease control rate, progression-free survival and overall survival.
Interim reports will be submitted to the U.S. Food and Drug Administration and the European Medicines Agency, providing an opportunity to review safety and efficacy data collected during the trial. Patients will be enrolled at up to 90 cancer centers globally. For more information about the trial, patients and physicians should call the U.S. toll-free number 855-552-7423, the EU toll-free number 800 00027423, or the international number +1 617-503-7423, or email ARIAD at ClinicalTrials@ariad.com.About Iclusig ® (ponatinib) tablets Iclusig is approved in the U.S., EU, Australia and Switzerland. In the U.S., Iclusig is a kinase inhibitor indicated for the:
- Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
- Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
- Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.
- Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.
- Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.
Iclusig ® is a registered trademark of ARIAD Pharmaceuticals, Inc.