FDA Expands Labeling for Leukemia Drug Iclusig

Kinase inhibitor treats CML and Ph+ AML

The FDA has given full approval to ponatinib (Iclusig, Ariad Pharmaceuticals) for the treatment of adults with chronic phase, accelerated-phase, or blast-phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated; and for the treatment of adults with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I positive Ph+ ALL.

Ponatinib is a kinase inhibitor. Its primary target is BCR-ABL, an abnormal tyrosine kinase that is expressed in CML and in Ph+ ALL. Ponatinib also targets BCR-ABL isoforms carrying mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

Ponatinib was initially approved in December 2012 under the FDA’s accelerated approval program. The therapy was also granted the FDA’s orphan drug designation because it is intended to treat a rare disease or condition. In the U.S., ponatinib is indicated for the treatment of adults with:

  • Chronic-phase, accelerated-phase, or blast-phase CML or Ph+ ALL for whom no TKI therapy is indicated
  • T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL

The full approval and label update for ponatinib was based on 48-month follow-up data (as of August 2015) from the pivotal phase 2 PACE trial of ponatinib in heavily pretreated patients with resistant or intolerant CML or Ph+ ALL. A total of 449 patients were treated with ponatinib at a starting dosage of 45 mg per day. An estimated 93% of patients had previously received two or more approved TKIs, and 56% of all patients had received three or more approved TKIs. Enrollment in the PACE trial was completed in October 2011.

Updated data on patients with chronic-phase CML (n = 270) from the ongoing trial indicated that, with a minimum follow-up of 48 months, 110 patients continued to receive ponatinib. Fifty-five percent of these patients achieved a major cytogenetic response (the trial’s primary endpoint), and 39% achieved a major molecular response. The findings were presented at the 2016 annual meeting of the American Society for Clinical Oncology.

Source: Ariad Pharmaceuticals; November 29, 2016.