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Ponatinib is a potent, third-generation oral tyrosine kinase inhibitor (TKI) that targets BCR-ABL1, an abnormal tyrosine kinase that is the hallmark of Philadelphia chromosome-positive (Ph+) leukemias. It was specifically designed to inhibit BCR-ABL1 with the T315I mutation, which confers resistance to all other first- and second-generation TKIs. In the context of acute lymphoblastic leukemia (ALL), ponatinib is often administered in combination with various chemotherapy agents (such as vincristine, dexamethasone, and anthracyclines) to improve remission rates and overcome resistance. Takeda Pharmaceuticals markets ponatinib under the brand name Iclusig. It has received accelerated approval for newly diagnosed Ph+ ALL in adults when used with chemotherapy and is also indicated for patients with CML or Ph+ ALL who are resistant or intolerant to prior TKI therapy.
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