FDA Approval Summary: Asciminib for Ph+ CML in Chronic Phase Treated with Two or More Tyrosine Kinase Inhibitors and for the T315I Mutation.

On October 29, 2021, FDA granted accelerated approval to asciminib (Scemblix; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL Study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% (95% CI: 30, 46) in the asciminib arm vs. 16% (95% CI: 8, 26) in the bosutinib arm (p-value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI: 34, 64) in the single-arm CABL001X2101 Study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, increases in creatine kinase, ALT, AST, lipase, and amylase. This manuscript describes the basis for approval of these indications.