The U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application for ponatinib to treat adults with chronic-phase chronic myeloid leukemia (CML) that is resistant or intolerant to at least two prior kinase inhibitors.
This updated label includes a dosing regimen starting with 45 mg and reducing to 15 mg upon achieving ≤1% BCR-ABL1IS to reduce the risk of adverse events (AEs).
The application’s approval is based on data from the phase II OPTIC and PACE trials. At 12 months, 42% of 88 patients in the OPTIC trial who were receiving the new dosing regimen achieved the primary endpoint of ≤1% BCR-ABL1IS and, at a median follow up of 28.5 months, 73% of those patients maintained the response. In the OPTIC trial, AEs occurring in >20% of patients included rash, hypertension, arthralgia, hyperlipidemia, hepatic dysfunction, pancreatitis, and abdominal pain.
Of 267 patients with chronic-phase CML enrolled in the PACE trial who were treated with ponatinib, 55% achieved the primary endpoint of major cytogenetic response by 12 months, including 70% of the 64 patients with chronic-phase CML and the T315I mutation.
Ponatinib has previously been approved for the treatment of adults with accelerated-phase or blast-phase CML or Ph-positive acute lymphocytic leukemia (ALL) for whom no other kinase inhibitor is indicated, as well as T315I-positive CML or T315I– and Ph-positive ALL.