Asciminib (Scemblix)

Mechanism of action

From the NCI Drug Dictionary: An orally bioavailable, allosteric Bcr-Abl tyrosine kinase inhibitor with potential antineoplastic activity. Designed to overcome resistance, asciminib binds to the Abl portion of the Bcr-Abl fusion protein at a location that is distinct from the ATP-binding domain, and is a so-called STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor. This binding results in the inhibition of Bcr-Abl-mediated proliferation and enhanced apoptosis of Philadelphia chromosome-positive (Ph+) hematological malignancies.

Diseases for which it is used

• Chronic myeloid leukemia

History of changes in FDA indication

• 2021-10-29: Granted accelerated approval for patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). (Based on ASCEMBL)
  • 2022-10-12: Converted to regular approval.
• 2021-10-29: Approved for adult patients with Ph+ CML in CP with the T315I mutation. (Based on CABL001X2101)
• 2024-10-29: Granted accelerated approval for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP). (Based on ASC4FIRST)

History of changes in EMA indication

• 2022-08-25: Initial authorization as Scemblix. Scemblix is indicated for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors. (Based on ASCEMBL & CABL001X2101)

History of changes in Health Canada indication

• 2022-06-22: Initial notice of compliance

History of changes in PMDA indication

• 2022-03-28: Newly indicated for the treatment of chronic myelogenous leukemia with resistance or intolerance to prior drug therapies.

Also known as

• Code name: ABL-001
• Brand name: Scemblix