Ponatinib Approved for CML and Ph+ ALL

January 2013, Vol 4, No 1 - FDA Approvals, News & Updates


The US Food and Drug Admin­istration (FDA) approved ponatinib (Iclusig; ARIAD Pharmaceuticals) under its accelerated program for the treatment of patients with chronic- phase (CP), accelerated-phase (AP), or blast-phase (BP) chronic myeloid leukemia (CML) that is resistant to or intolerant to tyrosine kinase inhibitor (TKI) therapy or to Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) that is resistant to or intolerant to TKI therapy. The recommended dose is 45 mg, taken orally once daily, with no regard to food.

“Clinical responses to Iclusig have been observed in patients regardless of their mutation status or stage of disease. It is a valuable new treatment option for leukemia patients,” said Jorge E. Cortes, MD, Professor and Deputy Chair, Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX.

Approximately 5000 new cases of CML are diagnosed annually in the United States.

Ponatinib’s approval was based on the single-arm PACE clinical trial, which included 449 patients with CML or Ph+ ALL that has become resistant or intolerant to TKI therapy. The primary end points were major cytogenetic response (MCyR) for patients with CP-CML and major hematologic response (MaHR) for patients with AP-CML, BP-CML, or Ph+ ALL. As a condition for the accelerated approval, the manufacturer will submit to the FDA 24-month follow-up data for all patients using this medication.

PACE results showed a 54% MCyR in patients with CP-CML; 70% of patients with CP-CML with T315I mutation achieved MCyR. At the time of data analysis, median MCyR had not yet been reached. For patients with AP-CML, BP-CML, or Ph+ ALL, MaHR rates were 52%, 31%, and 41%, respectively. In patients with AP-CML, BP-CML, or Ph+ ALL, median MaHRs were 9.5, 4.7, and 3.2 months, respectively.

The most common side effects are hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea. Ponatinib was approved with a Boxed Warning regarding the risks for arterial thrombosis and liver toxicity. (December 14, 2012)