The FDA today approved Iclusig (ponatinib) for the treatment of adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases.
Iclusig works by blocking certain proteins that promote the development of cancerous cells. The drug is taken once a daily to treat patients with chronic, accelerated, and blast phases of CML and Ph+ ALL whose leukemia is resistant or intolerant to a class of drugs called tyrosine kinase inhibitors (TKIs). Iclusig targets CML cells that have a particular mutation, known as T3151, which makes these cells resistant to currently approved TKIs.
Bosulif (bosutinib) and Synribo (omacetaxine mepesuccinate) won FDA approval in September 2012 and October 2012, respectively, to treat various phases of CML. Marqibo (vincristine sulphate liposome injection) was approved in August 2012 to treat Philadelphia chromosome negative ALL.
Iclusig’s safety and effectiveness were evaluated in a single clinical trial of 449 patients with various phases of CML and Ph+ ALL. All participants were treated with Iclusig. The drug’s effectiveness was demonstrated by a reduction in the percentage of cells expressing the Philadelphia chromosome genetic mutation found in most CML patients, major cytogenetic response (MCyR). 54% of all patients and 70% of patients with the T315I mutation achieved MCyR. The median duration of MCyR had not yet been reached at the time of analysis.
In accelerated and blast phase CML and Ph+ ALL, Iclusig’s effectiveness was determined by the number of patients who experienced a normalization of white blood cell counts or had no evidence of leukemia (major hematologic response or MaHR). Results showed:
- 52% of patients with accelerated phase CML experienced MaHR for a median duration of 9.5 months;
- 31% of patients with blast phase CML achieved MaHR for a median duration of 4.7 months; and
- 41% of patients with Ph+ ALL achieved MaHR for a median duration of 3.2 months.
Iclusig is being approved with a Boxed Warning notifying patients and health care professionals 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.
Iclusig is marketed by ARIAD Pharmaceuticals, based in Cambridge, Mass. Bosulif is marketed by New York City-based Pfizer, and Synribo is marketed by Frazer, Pa.-based Teva Pharmaceuticals. Marqibo is marketed by Talon Therapeutics Inc. based in South San Francisco, Calif.