FDA Approval for Ponatinib Hydrochloride
Brand name(s): Iclusig
- Approved for chronic myeloid leukemia or Philadelphia chromosome–positive acute lymphoblastic leukemia
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.
On December 14, 2012, the Food and Drug Administration (FDA) granted accelerated approval to ponatinib hydrochloride (Iclusig™ tablets, made by ARIAD Pharmaceuticals, Inc.) for the treatment of adult patients with chronic-phase (CP), accelerated-phase (AP), or blast-phase (BP) chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy.
The approval was based on the results of the PACE trial, a multicenter international single-arm clinical trial of 449 patients with disease that was resistant or intolerant to prior tyrosine kinase inhibitor therapy. The primary endpoints were major cytogenetic response (MCyR), for patients with CP-CML, and major hematologic response (MaHR), for patients with AP-CML, BP-CML or Ph+ALL. FDA required that the sponsor commit to submit 24-month follow-up data for all patients as a condition for the accelerated approval.
The efficacy results demonstrated a 54 percent MCyR rate in patients with CP-CML. Seventy percent of patients with CP-CML with the T315I mutation in BCR-ABL achieved MCyR. The median duration of MCyR had not yet been reached at the time of analysis. The MaHR rate was 52 percent in patients with AP-CML, 31 percent in patients with BP-CML, and 41 percent in patients with Ph+ ALL. The median duration of MaHR was 9.5 months in patients with AP-CML, 4.7 months in patients with BP-CML, and 3.2 months in patients with Ph+ ALL.
Ponatinib hydrochloride is being approved with a Boxed Warning alerting patients and healthcare professionals that arterial thrombosis and liver toxicity have occurred in patients treated with ponatinib hydrochloride. The most common side effects reported in the clinical trial include hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea.
The recommended dose and schedule for ponatinib hydrochloride is 45 mg taken orally once daily with or without food.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.