The FDA has granted ponatinib (Iclusig) full approval for the treatment of adult patients 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 adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL.
This full approval and label update is based on 48-month follow-up data (as of August 2015) from the pivotal phase II PACE clinical trial of ponatinib in heavily pretreated patients with resistant or intolerant CML or Ph+ ALL.
The efficacy and safety of ponatinib in CML and Ph+ ALL patients resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation, were evaluated in the PACE trial. A total of 449 patients were treated with ponatinib at a starting dose of 45 mg/day.
An estimated 93 percent of patients previously received two or more approved TKIs, and 56 percent of all patients received three or more approved TKIs. Enrollment in the PACE trial was completed in October 2011. Updated data on CP-CML patients (n=270) from the ongoing trial indicate that, with a minimum follow-up of 48 months (data as of August 3, 2015), 110 patients continued to receive ponatinib.
Patients are currently being enrolled in the OPTIC post-marketing trial of ponatinib, which is expected to inform the optimal dosing of Iclusig. This randomized, dose-ranging trial is enrolling patients with CP-CML who are resistant to at least two approved TKIs. Patients are randomized equally to receive once-daily administration of 45 mg (cohort A), 30 mg (cohort B), or 15 mg (cohort C) of ponatinib.
Patients in cohorts A and B will have their daily dose reduced to 15 mg upon achievement of MCyR. The primary endpoint of the trial is MCyR by 12 months for each cohort. Initial data from the OPTIC trial is expected to be submitted to the American Society of Hematology meeting in 2017.