Ponatinib: A drug review

Abstract

The discovery of Philadelphia (Ph) chromosome in 1959 was a landmark moment in the history of targeted therapies for cancer. The BCR-ABL fusion gene formed as a result of this translocation is the key pathogenetic event of chronic myeloid leukemia (CML) and Ph-positive acute lymphoblastic leukemia (ALL). Currently, there are five tyrosine kinase inhibitors (TKIs) available in the clinic to target the BCR-ABL kinase. The last one to be added to the list is ponatinib. Ponatinib is highly effective even in the presence of mutations such as T315I that render all other TKIs ineffective. The initial enthusiasm following the impressive results from the Ponatinib Ph-positive ALL and CML Evaluation (PACE) trial was dampened by the emergence of arterial occlusive events. With a dose-adapted strategy, the drug seems to be ready for a comeback. We review the drug ponatinib, including the history, chemistry, mechanism of action, pharmacokinetics, clinical trial data, ongoing clinical trials, and adverse events.

Keywords

• chronic myeloid leukemia
• philadelphia-positive acute lymphoblastic leukemia
• ponatinib
• tyrosine kinase inhibitor
• cml
• all
• t315i