Ariad Pharmaceuticals reported long-term data from its pivotal Phase 2 trial of Iclusig (ponatinib) in chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
Iclusig is a kinase inhibitor of BCR-ABL, a malignant tyrosine kinase found in both CML and Ph+ ALL. The company won approval from the U.S. Food and Drug Administration (FDA) to continue marketing Iclusig after a label update of the drug’s prescribing information and safety recommendations. Ariad also received the positive opinion of the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) for Iclusig as treatment for CML and acute lymphoblastic leukemia (ALL) in the EU.
The mid-stage PACE trial investigated the safety and efficacy of Iclusig in patients with CML and Ph+ ALL who are resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. After three years, the drug continued to demonstrate anti-leukemic activity. Deep and sustainable responses have also been maintained in chronic-phase CML (CP-CML) patients. Eighty-three percent of these were estimated to remain in major cytogenetic response (MCyR) at three years. Finally, the company reported that the rate of response maintenance in CP-CML patients was greater than 90 percent in patients who underwent ponatinib dose reductions.
“With a median follow-up of 3 years, there is no question that these are very meaningful responses in a refractory CML patient population… Careful benefit-risk evaluation should guide the decision to initiate ponatinib therapy, particularly in patients who may be at increased risk for arterial thrombotic events. Ponatinib continues to be a valuable treatment option for patients with refractory CML and Ph+ ALL for whom the need and potential benefit outweigh the risk,” said Jorge E. Cortes, Professor and Department Chair of Department of Leukemia, The University of Texas MD Anderson Cancer Center.
“These data show that the majority of patients in the PACE trial retained response, even when lowering the daily dose of Iclusig. The safety and efficacy of Iclusig at starting doses lower than 45 mg will be studied in a randomized trial set to begin next year,” said Dr. Frank G. Haluska, SVP of clinical R&D and CMO at Ariad.
Ariad presented the results at the 56th Annual Meeting of the American Society of Hematology (ASH) in San Francisco.