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FDA Okays Iclusig (Ponatinib) for Leukemia

Agency approval comes 3 months ahead of schedule (Dec. 14)

The FDA has approved Iclusig (ponatinib, Ariad Pharmaceuticals) for the treatment of adults with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

The drug was approved more than 3 months ahead of the product’s prescription user fee goal date of March 27, 2013 — the date the agency was scheduled to complete review of the drug application. The FDA reviewed the application under the agency’s priority review program, which provides an expedited 6-month review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or for drugs that offer significant improvement compared with marketed products.

Ponatinib blocks certain proteins that promote the development of cancerous cells. 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 to or intolerant of tyrosine kinase inhibitors (TKIs). Ponatinib targets CML cells that have the T315I gene mutation, which makes these cells resistant to currently approved TKIs.

The FDA approved Bosulif (bosutinib, Pfizer) in September 2012 and Synribo (omacetaxine mepesuccinate, Cephalon) in October 2012 to treat various phases of CML. Marqibo (vincristine sulfate liposome injection, Talon Therapeutics) was approved in August 2012 to treat Philadelphia chromosome-negative ALL.

The safety and effectiveness of ponatinib were evaluated in a clinical study of 449 patients with various phases of CML and Ph+ ALL. All of the participants were treated with ponatinib.

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 (the major cytogenetic response [MCyR]). Fifty-four percent 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, the effectiveness of ponatinib was determined by the number of patients who experienced normalization of white blood-cell counts or who had no evidence of leukemia (major hematologic response [MaHR]). The results showed:

  • 52% of patients with accelerated-phase CML experienced MaHR for a median period of 9.5 months;
  • 31% of patients with blast-phase CML achieved MaHR for a median period of 4.7 months; and
  • 41% of patients with Ph+ ALL achieved MaHR for a median period of 3.2 months.

Iclusig (ponatinib) was 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 included high blood pressure, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea.

Source: FDA; December 14, 2012.

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