New drug approval for adults with CML, Ph+ ALL

Following priority review, FDA approved ponatinib (Iclusig , ARIAD Pharmaceuticals) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases.

Ponatinib has been 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.

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 or intolerant to a class of drugs called tyrosine kinase inhibitors (TKIs). Ponatinib targets CML cells that have a particular mutation, known as T315I, which makes these cells resistant to currently approved TKIs.

"[The] FDA approval of Iclusig is an important advance in the treatment of patients with CML and Ph+ ALL who are resistant or intolerant to prior TKI therapy," Harvey J. Berger, MD, chairman and chief executive officer of ARIAD, said in a press release.

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


Ponatinib'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 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, 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, ponatinib'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.

Ponatinib is being approved with a Boxed Warning alerting patients and healthcare 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.

Approximately 5,000 new cases of CML are diagnosed each year in the United States. CML patients treated with TKIs can develop resistance or intolerance over time to these therapies.

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