On October 29, 2021, the FDA accelerated the approval of asciminib (Scemblix; Novartis AG), an oral kinase inhibitor, for the treatment of patients with chronic-phase Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) after receiving ≥2 tyrosine kinase inhibitors (TKIs), as well as for adults with chronic-phase Ph-positive CML that is associated with T315I mutation. The FDA granted asciminib breakthrough therapy and orphan drug designations for these indications.
The FDA approval of these 2 indications was based on results from 2 clinical trials. The first study was ASCEMBL, a multicenter, randomized, active-controlled, open-label clinical trial of 233 patients with chronic phase Ph-positive CML who previously received ≥2 TKIs. Patients were randomized in a 2:1 ratio and were stratified according to major cytogenetic response to asciminib 40 mg twice daily or to bosutinib (Bosulif) 500 mg once daily, until unacceptable adverse effects or treatment failure.
The main end point was major molecular response (MMR) at 24 weeks. The MMR rate was 25% (95% confidence interval [CI], 19-33) with asciminib versus 13% (95% CI, 6.5-23; P = .029) with bosutinib. At a median of 20-month follow-up, the median duration of MMR has not been reached.
The second study was CABL001X2101, a multicenter, open-label clinical trial that included 45 patients with chronic-phase Ph-positive CML and T315I mutation. All patients received asciminib 200 mg twice daily until unacceptable adverse events or treatment failure. The main end point was MMR. At 24 weeks, 42% (95% CI, 28%-58%) of the patients reached MMR. By 96 weeks, that rate was increased to 49% (95% CI, 34%-64%). The median duration of treatment was 108 weeks (range, 2-215 weeks).
The most common (≥20%) adverse events were upper respiratory tract infection, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities were decreased platelet counts, increased triglycerides, decreased neutrophil counts and hemoglobin, and increased creatine kinase, alanine aminotransferase, lipase, and amylase.
The recommended asciminib dose for patients with Ph-positive CML is 80 mg once daily, or 40 mg twice daily. The recommended dose for patients with T315I mutation is 200 mg twice daily.