Aceminib for the treatment of chronic myelogenous leukemia

On October 29, 2021, the U.S. Food and Drug Administration granted accelerated approval of asciminib (Scemblix, Novartis) as a kinase inhibitor (TKI) for the treatment of patients with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) who have received two or more prior tyrosine therapies, and approved asciminib (asciminib) for the treatment of adult patients with Ph+ CML in T315I-mutated CP.

ASCEMBL (NCT03106779) is a multicenter, randomized, active-controlled, open-label clinical trial evaluating aciminib in patients with CP Ph+ CML who have received two or more prior TKIs. A total of 233 patients were randomized (2:1) and stratified by major cytogenetic response (MCyR) status to receive either aximinib 40 mg twice daily or bosutinib 500 mg once daily. Patients continued treatment until unacceptable toxicity or treatment failure. The primary efficacy outcome measure was major molecular response (MMR) at 24 weeks. The MMR rate was 25% (95% CI: 19, 33) in patients treated with aximinib and 13% (95% CI: 6.5, 23; p=0.029) in patients treated with bosutinib. With a median follow-up of 20 months, the median duration of MMR has not been reached.

CABL001X2101 (NCT02081378) is a multicenter, open-label clinical trial evaluating aceminib in patients with T315I-mutated CP Ph+ CML. Efficacy was based on 45 patients with the T315I mutation who received aceminib 200 mg twice daily. Patients continued treatment until unacceptable toxicity or treatment failure. The primary efficacy outcome measure was MMR. 42% (19/45, 95% CI: 28% to 58%) of patients achieved MMR at 24 weeks. At 96 weeks, 49% (22/45, 95% CI: 34% to 64%) of patients achieved MMR. Median treatment duration was 108 weeks (range, 2 to 215 weeks).

The most common adverse reactions (≥20%) were upper respiratory tract infection, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities are decreased platelet count, increased triglycerides, decreased neutrophil count, and hemoglobin, and increased creatine kinase, alanine aminotransferase, lipase, and amylase.

For patients with CP Ph+ CML who have received two or more prior TKIs The recommended dose of aximinib is 80 mg orally once daily at approximately the same time each day, or 40 mg twice daily approximately 12 hours apart. For patients with Ph+ CML in CP harboring the T315I mutation, the recommended dose of aximinib is 200 mg orally administered twice daily approximately 12 hours apart.

In summary, with its unique target selection, significant clinical effect, and good safety and tolerability, aceminib provides a new and effective treatment option for patients with chronic myelogenous leukemia.