asciminib

Asciminib, sold under the brand name Scemblix, is a targeted therapy for BCR-ABL1–positive leukemias, including chronic myeloid leukemia (CML). It is the first approved allosteric inhibitor of BCR-ABL1, binding selectively to the myristoyl pocket of the kinase and inducing autoinhibition. This mechanism is distinct from ATP-competitive TKIs, offering a treatment option for patients with resistance or intolerance to prior TKIs.

In CML, asciminib is indicated for adults with resistance or intolerance to at least two prior tyrosine kinase inhibitors. It has demonstrated activity in patients harboring the T315I mutation, which limits response to many ATP-competitive inhibitors. The FDA approved Scemblix in 2021 for this setting; other regions have implemented similar indications.

Administration and monitoring: It is taken orally, once daily, with or without food; dose and duration are determined by clinical context. Patients are monitored for response and adverse events, including cytopenias and hepatic enzyme elevations. As with other TKIs, potential drug interactions exist, particularly with strong CYP3A inhibitors or inducers, requiring dose adjustments.

Adverse effects: Common adverse events include fatigue, headache, nausea, and cytopenias (anemia, thrombocytopenia). Serious adverse events can occur; hepatic toxicity and hypertension have been reported in some cases.

Research: Ongoing trials are evaluating asciminib in earlier lines of therapy, combination regimens, and other BCR-ABL1–driven conditions.