Pipeline – Ponatinib



BCR-ABL Inhibitor


Ponatinib, the only pan-BCR-ABL1 inhibitor, is a third-generation TKI designed to potentially inhibit BCR-ABL1 with or without any single resistance mutation, including T315I

Mechanism of Action1-4

  • Ponatinib was designed using a computational structure-based approach to incorporate two key design elements that allow it to confer high potency against both native and mutant BCR-ABL
    1. Binding of ponatinib to BCR-ABL1 is distributed across multiple sites, which results in high-affinity binding to unmutated BCR-ABL1 and allows it to withstand the loss of binding energy caused by any single mutation
    2. A carbon-carbon triple bond linkage that allows key interactions with the side chain of the T315I gatekeeper mutant
  • In pre-clinical models, ponatinib suppressed all clinically relevant BCR-ABL1 single mutations, including T315I at clinically achievable concentrations

Clinical Trials

Study Name

A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponalinib Versus lmatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)




Phase 3



Study Name

A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients With Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses (OPTIC)




Phase 2


Active, not recruiting


1. Clackson T. Design and development of ponatinib, a pan-BCR-ABL inhibitor for CML. Cancer Res. 2013;73(8). Web Link

2. O'Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16(5):401-412. doi:10.1016/j.ccr.2009.09.028 Iclusig® [package insert]. ARIAD Pharmaceuticals, Inc.

3. Iclusig® [package insert]. ARIAD Pharmaceuticals, Inc.

4. Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075-2088. doi:10.1056/NEJMoa1205127

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