Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).
Asciminib is a protein kinase inhibitor.
Pregnancy category AU: D
Routes of administration- By mouth
Tyrosine kinase inhibitor
The most common adverse reactions include upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea.
Asciminib targets the ABL myristoyl pocket.
The wild-type ABL has a myristoylated N-terminus, which binds to an allosteric site, but the ABL fusion protein does not have the myristoylated domain.
In the wild-type protein, when myristoylated N-terminus binds to the allosteric site, the kinase has reduced activity.
Since the mutant fusion protein does not have the myristoylated N-terminus domain, it is not subject to this form of regulation, and thus the fusion protein is constitutively active.
Asciminib binds to the allosteric site, resulting in an inhibition of bcr-abl activity.
Unlike other bcr-abl inhibitors, such as imatinib, asciminib does not bind to the ATP-binding site on the active site of the enzyme.
Asciminib and active site bcr-abl inhibitors have non-overlapping resistance mutations.
The mutations A337V and P223S overcome the inhibitory activity of asciminib, but asciminib is not affected by the notorious T315I mutation that affects most ATP-competitive active site inhibitors, except ponatinib.
Common side effects of Asciminib are symptoms of a cold, muscle pain, joint pain, bone pain, fatigue, nausea, diarrhea, rash as well as the patient displaying abnormal blood tests.
Serious side effects of the medication include high blood pressure, low blood cell count, problems with the pancreas, and heart issues.
Side effects of the medication on the pancreas may be observed via changes in serum lipase and amylase levels.
Asciminib is a substrate of the CYP3A4 enzyme,an inhibitor of CYP3A4, CYP2C9, and P-glycoprotein.
Asciminib reaches steady state in 3 days.
In a clinical trial of 48 participants with chronic myeloid leukemia with a certain type of mutation (T315I mutation.
The benefit of asciminib was evaluated in Philadelphia chromosome-positive chronic myeloid leukemia participants with the T315 mutation by measuring the reduction of abnormal cells in participants’ blood to a very low level after 96 weeks of treatment.
It is intended for the treatment of adults with Philadelphia chromosome‑positive chronic myeloid leukemia in chronic phase who have previously been treated with two or more tyrosine kinase inhibitors.
In July 2024, the US Food and Drug Administration granted Priority Review status to asciminib for the treatment of newly diagnosed adult patients with Philadelphia chromosome-positive CML in chronic phase.