The U.S. Food and Drug Administration (FDA) has approved Iclusig™ (ponatinib) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases.
Chronic myeloid leukemia (CML) is the abnormal growth of relatively mature myeloid (white blood) cells. Acute lymphoblastic leukemia (ALL) is a malignant disease or cancer of the blood characterized by the rapid uncontrolled growth of abnormal, immature white blood cells known as lymphoblasts. There are approximately 5,000 new cases each of adult ALL and CLL every year in the United States.
Most cases of CML—and about 40 percent of ALL cases—are characterized by a chromosomal abnormality—the Philadelphia chromosome—in which genetic material is exchanged between chromosome 9 and chromosome 22. This exchange brings together two genes: BCR and ABL. The combination of these two genes into the single BCR-ABL gene results in the production of a protein that contributes to uncontrolled cell growth.
Iclusig is an oral, multi-targeted tyrosine-kinase inhibitor that primarily functions as a BCR-ABL inhibitor. It was designed to overcome the T3151 mutation, which is notoriously resistant and difficult to treat. The drug is taken once a day 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’s approval was based on data from a single clinical trial that involved 449 patients with various phases of CML and Ph+ ALL. Iclusig’s effectiveness in CML patients was based on the reduction of percentage of cells that expressed the Philadelphia chromosome—or major cytogenetic response (MCyR). Fifty-four percent of all patients and 70 percent of patients with the T3151 mutation achieved MCyR.
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). The results indicated that:
- 52 percent of patients with accelerated phase CML experienced MaHR for a median duration of 9.5 months;
- 31 percent of patients with blast phase CML achieved MaHR for a median duration of 4.7 months; and
- 41 percent of patients with Ph+ ALL achieved MaHR for a median duration of 3.2 months.
Iclusig was approved under the FDA’s accelerated approval program, which allows patients earlier access to promising drugs while the manufacturer conducts ongoing studies regarding benefit and safety. Iclusig also received the FDA’s orphan drug status because it is intended to treat a rare disease or condition.
Iclusig is being approved with a Boxed Warning alerting 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.
FDA approves Iclusig to treat two rare types of leukemia. [FDA News Release]. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm332252.htm