In this article, we will discuss Asciminib (Mechanism of Action). So, let’s get started.
Mechanism of Action
Asciminib is an ABL/BCR-ABL1 tyrosine kinase inhibitor. Asciminib inhibits the ABL1 kinase activity of the BCR-ABL1 fusion protein, by binding to the ABL myristoyl pocket. In studies conducted in vitro or in animal models of CML, asciminib showed activity against wild-type BCR-ABL1 and several mutant forms of the kinase, including the T315I mutation.
Pharmacodynamics
Exposure-Response Relationships
Over asciminib dosages of 10 mg to 200 mg twice daily (0.25 to 5 times the recommended 80 mg daily dosage), a lower exposure was associated with a smaller decrease in BCR-ABL1 level and a lower MMR rate at Week 24. Over asciminib dosages of 10 mg to 280 mg twice daily (0.25 to 7 times the recommended 80 mg daily dosage), a higher exposure was associated with slightly higher incidence of some adverse reactions (e.g., Grade ≥3 lipase increase, Grade ≥3 hemoglobin decrease, Grade ≥2 ALT increase, Grade ≥2 AST increase, Grade ≥2 bilirubin increase, and any grade lipase increase).
Cardiac Electrophysiology
Asciminib does not cause a large mean increase in QTc interval (i.e., >20 msec) at the maximum recommended clinical dosage (200 mg twice daily). Based on available clinical data, small mean QTc increase (<10 msec) cannot be excluded.