The U.S. Food and Drug Administration has approved the use of ponatinib (Iclusig, marketed by Ariad Pharmaceuticals) to treat adults with chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. The drug—taken once a day—is used to treat patients with chronic, accelerated, and blast phases of the disease who are resistant to tyrosine kinase inhibitors by blocking proteins that help cancer cells develop. In CML, Iclusig targets cells with the TKI-resistant-T3151 mutation, which occurs in 10 to 15 percent of those patients and for whom no treatment options currently exist.
“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,” Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release. “Iclusig is the third drug approved to treat CML and the second drug approved to treat ALL [in 2012].”
The FDA approved Bosulif (bosutinib) (OT, 10/10/12) in September 2012 and Synribo (omacetaxine mepesuccinate) (OT, 11/25/12) in October 2012 to treat various phases of CML. Marqibo (vincristine sulfate liposome injection) (OT, 9/10/12) was approved in August 2012 to treat Philadelphia chromosome negative ALL.
Iclusig's approval came more than three months ahead of the product's prescription user fee goal date of March 27, 2013. Iclusig was reviewed under the FDA's priority review program, which provides for an expedited six-month review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared with marketed products.
Iclusig's safety and effectiveness were evaluated in a clinical trial of 449 patients with various phases of CML and Ph+ALL in which all patients were treated with the drug. The study showed:
- 54 percent of all patients and 70 percent of patients with the T315I mutation achieved a major cytogenetic response;
- 52 percent of patients with accelerated-phase CML experienced a major hematologic response for a median duration of 9.5 months;
- 31 percent of patients with blast-phase CML achieved major hematologic response for a median duration of 4.7 months; and
- 41 percent of patients with Ph+ ALL achieved a major hematologic response for a median duration of 3.2 months.
The label includes a Boxed Warning noting that the drug can cause blood clots and liver toxicity. The most common side effects reported during clinical trials include high blood pressure, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea.