FDA Approves Ponatinib to Treat Leukemia

The US Food and Drug Administration (FDA) has approved ponatinib (Iclusig) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). The new drug, taken daily, is intended for CML and Ph+ ALL patients whose leukemia is resistant or intolerant to tyrosine kinase inhibitors (TKIs).

According to Ariad Pharmaceuticals, the company that markets the drug, ponatinib targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment with existing TKIs.

“The approval of Iclusig is important because it provides a treatment option to patients with CML who are not responding to other drugs, particularly those with the T315I mutation who have had few therapeutic options,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “Iclusig is the third drug approved to treat CML and the second drug approved to treat ALL this year.”

This year the FDA has approved bosutinib (Bosulif) and omacetaxine mepesuccinate (Synribo) to treat various phases of CML, and vincristine sulfate liposome injection (Marqibo) for the treatment of Philadelphia chromosome–negative ALL.

The trial that led to the approval, the PACE trial (Ponatinib Ph+ ALL and CML Evaluation), was a phase II clinical trial of 449 patients with various phases of CML and Ph+ ALL. All were treated with ponatinib. The data show that 54% of chronic-phase CML patients in the trial, including 70% percent of patients who have a T315I mutation, achieved a major cytogenetic response.

In accelerated- and blast-phase CML and Ph+ ALL, ponatinib’s effectiveness was determined by the number of patients who experienced a major hematologic response. The data show that major hematologic response was observed in 58% of patients with accelerated-phase CML (57% of resistant/intolerant patients and 50% with T315I mutation), and 34% of those with blast-phase CML/ Ph+ ALL (35% of resistant/intolerant patients and 33% with T315I mutation).

Other results show that 52% of patients with accelerated-phase CML experienced major hematologic response for a median duration of 9.5 months; 31% of patients with blast-phase CML achieved major hematologic response for a median duration of 4.7 months; and 41% of patients with Ph+ ALL achieved major hematologic response for a median duration of 3.2 months.

The drug is approved with a boxed warning as the drug can cause blood clots and liver toxicity. The most common adverse events considered related to ponatinib included thrombocytopenia, rash, dry skin, abdominal pain, and headache. Elevated serum lipase, fatigue and arthralgia were observed less frequently. Incidence of pancreatitis was previously determined to be the dose-limiting toxicity of ponatinib in the phase I trial.