Scemblix
Ph+ CML in chronic phase, previously treated with two or more tyrosine kinase inhibitors; Ph+ CML in chronic phase with the T315I mutation.
Without T315I: 80 mg orally once daily or 40 mg twice daily
With T315I: 200 mg orally twice daily
Take with or without food
Avoid concomitant use of strong CYP3A inducers and CYP2C9 substrates with narrow therapeutic index
Tablets: 20 mg, 40 mg
None listed.
- Myelosuppression: Grade 3-4 thrombocytopenia (21%), neutropenia (18%), anemia (7%). Monitor CBC every 2 weeks × 3 months, then monthly.
- Pancreatic Toxicity: Lipase elevation in 28% (Grade 3-4 in 6%). Monitor lipase monthly × 3 months, then periodically. Withhold for Grade 3+.
- Hepatotoxicity: ALT/AST elevations. Monitor LFTs monthly × 3 months, then periodically.
- Cardiovascular Toxicity: Hypertension (17%), QT prolongation (rare). Monitor BP.
Musculoskeletal pain (26%), upper respiratory tract infection (19%), fatigue (17%), hypertension (17%), diarrhea (16%), rash (16%), nausea (15%), headache (13%), arthralgia (13%), abdominal pain (12%), lipase elevation (28%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Asciminib is a first-in-class BCR-ABL1 inhibitor that binds specifically to the ABL myristoyl pocket (STAMP — Specifically Targeting the ABL Myristoyl Pocket), a unique allosteric regulatory site. Unlike ATP-competitive TKIs (imatinib, dasatinib, nilotinib), asciminib does not bind the ATP-binding site, which means it maintains activity against most ATP-site resistance mutations including T315I. The myristoyl pocket is essential for maintaining ABL kinase in its autoinhibited conformation; binding of asciminib locks ABL in this inactive state.
Tmax: 2-3 hours. Half-life: approximately 7-9 hours. Protein binding: ~97%. Metabolized by CYP3A4 and UGT2B7. Steady-state by Day 3-4. Excreted in feces (80%) and urine (11%).
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- ASCEMBL — Asciminib vs. bosutinib in CML previously treated with ≥2 TKIs. Phase III, n=233.