Products and
Pipeline

«Back

Ponatinib

BCR-ABL Inhibitor Philadelphia Chromosome Positive Acute, Lymphoblastic Leukemia, Chronic Myeloid Leukemia

Overview1-3

Ponatinib, the only third-generation TKI, is a pan-BCR-ABLl inhibitor rationally designed to potently inhibit native BCR-ABLl and all single mutations, including T3151

MOA1-5

  • Ponatinib was designed to incorporate 2 key elements
    1. Optimal fit to the ABLl binding site with distributed bind ing energy, which is thought to withstand the loss of binding energy caused by any of the single mutations
    2. A carbon-carbon trip le bond linkage that allows key interactions with the side cha in of the T3151 gatekeeper mutant
  • These features confer high potency against both native and mutant BCR-ABLl, underlying its pan-BCR-ABLl inhibitor profile
  • Preclinical experiments demonstrated that ponatinib inhibits the outgrowth of mutant BCR-ABLl clones; at 40 nM ponatinib, complete suppression of in vitro resistance was achieved across native and all mutant clones.
  • Ponatinib induced a selective reduction of viable cell numbers (ICS0 values - 500-fold lower) in primary CML cells over normal cells

Clinical Trials
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)

CT.GOV ID

NCT02467270

Phase

Phase 2

Status

Active. not recruiting
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)

CT.GOV ID

NCT03589326

Phase

Phase 3

Status

Recruiting
Study Name

A Pivotal Phase 1/2, Single-Arm, Open-label Study to Evaluate the Safety and Efficacy of Ponatinib With Chemotherapy in Pediatric Patients With Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Who Have Relapsed or Are Resistant or Intolerant to a Prior Tyrosine Kinase Inhibitor-Containing Therapy, or Who Have the T3151 Mutation

CT.GOV ID

NCT04501614

Phase

Phase 1/2

Status

Recruiting

References

1. Clakson T. Cancer Res. 2013;73(8)(suppl):SY19-04.

2. O'Hare T, et al. Cancer Cell. 2009;16:401-412.

3. ICLUSIG® US Prescribing Information, ARIAD Pharmaceuticals Inc.

Chat with
Med Info!
chatbot
×

Takeda Live Chat

×
Confirm Exit?

On exiting, all chat history will be cleared