The Therapeutic Goods Administration (TGA) has approved marketing of ponatinib (Iclusig) in Australia.
The drug is now approved to treat adults with chronic myeloid leukemia (CML) who could not tolerate or were resistant to at least 2 prior tyrosine kinase inhibitors (TKIs), or those patients with a T315I mutation.
Ponatinib is also approved to treat certain adults with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
These patients must be resistant to or intolerant of dasatinib and ineligible for treatment with imatinib, or they must have a T315I mutation.
Ponatinib is the only TKI approved in Australia for an indication that includes CML and Ph+ ALL patients with the T315I mutation.
The drug’s developers, Ariad Pharmaceuticals, Inc., and Specialized Therapeutics Australia Pty. Ltd., expect to launch ponatinib in early 2015.
The PACE trial
The TGA’s decision to approve ponatinib was based on results from the phase 2 PACE trial, which included patients with CML or Ph+ ALL who were resistant to or intolerant of prior TKI therapy, or who had the T315I mutation.
The median follow-up times were 15.3 months in chronic-phase CML patients, 15.8 months in accelerated-phase CML patients, and 6.2 months in patients with blast-phase CML or Ph+ ALL.
In chronic-phase CML, the primary endpoint was major cytogenetic response, and it occurred in 56% of patients. Among chronic-phase patients with the T315I mutation, 70% achieved a major cytogenetic response. Among patients who had failed treatment with dasatinib or nilotinib, 51% achieved a major cytogenetic response.
In accelerated-phase CML, the primary endpoint was major hematologic response. This occurred in 57% of all patients in this group, 50% of patients with the T315I mutation, and 58% of patients who had failed treatment with dasatinib or nilotinib.
The primary endpoint was major hematologic response in blast-phase CML/Ph+ ALL as well. Thirty-four percent of all patients in this group met this endpoint, as did 33% of patients with the T315I mutation and 35% of patients who had failed treatment with dasatinib or nilotinib.
Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).
Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). And serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.
Safety concerns
Ponatinib is also approved to treat CML and Ph+ ALL in the European Union and the US. However, the drug was pulled from the US market for a little over 2 months, and ponatinib trials were placed on partial hold, after extended follow-up from the PACE trial showed an increase in thrombotic events.
The drug went back on the market last January, with new safety measures in place.
Ponatinib was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of the drug. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.
