FDA Approves Asciminib for Ph+ CML

On October 29, 2021, the FDA granted accelerated approval to asciminib (Scemblix, Novartis AG) for the use in the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) with or without the T315I mutation who were previously treated with 2 or more tyrosine kinase inhibitors (TKIs).

This approval was based on efficacy outcomes from 2 studies.

The first was the multicenter, randomized, active-controlled, open-label ASCEMBL clinical trial, which evaluated asciminib in patients with Ph+ CML in CP, previously treated with 2 or more TKIs. The main efficacy outcome was major molecular response (MMR) at 24 weeks.

Patients (n=233) were randomized 2:1 and stratified according to major cytogenetic response (MCyR) status to receive either asciminib 40 mg twice daily or bosutinib 500 mg once daily. Patients continued treatment until unacceptable toxicity or treatment failure occurred. The MMR rate was 25 percent (95% CI, 19-33) for the asciminib arm compared with 13 percent (95& CI, 6.5-23; P=0.029) in the bosutinib arm. At the median follow up of 20 months, the median duration of MMR was not met.

The second was the multicenter, open-label CABL001X2101 clinical trial, which evaluated asciminib in patients with Ph+ CML in CP with the T315I mutation. The main efficacy outcome measure was MMR.

Efficacy was based on patients (n=45) with the T315I mutation who received asciminib 200 mg twice daily. Patients continued treatment until unacceptable toxicity or treatment failure occurred. MMR was achieved by 24 weeks in 42 percent (n=19, 95% CI, 28%-58%) of patients, and by 96 weeks in 49 percent (n=22, 95% CI, 34%-64%). The median duration of treatment was 108 weeks.

The most common (≥20%) adverse reactions from both studies include upper respiratory tract infections, 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 FDA said it recommends the dosage of asciminib for patients with Ph+ CML in CP is 80 mg taken orally once daily at the same time each day or 40 mg twice daily at 12-hour intervals. The recommended dosage of asciminib for patients with Ph+ CML in CP with the T315I mutation is 200mg taken orally twice daily at 12-hour intervals.—Emily Bader