On October 29, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to asciminib (Scemblix®) for patients with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) who were previously treated with two or more tyrosine kinase inhibitors (TKIs). FDA also approved asciminib for adult patients with Ph+ CML in CP with the T315I variation.
A multicenter, randomized, active-controlled, open-label clinical trial (ASCEMBL; NCT03106779) evaluated asciminib in patients with Ph+ CML in CP previously treated with two or more TKIs. A total of 233 patients were randomized 2:1 and stratified according to major cytogenetic response status to receive either asciminib 40 mg twice daily or bosutinib 500 mg once daily. Patients continued treatment until they experienced unacceptable toxicity or treatment failure. The main efficacy outcome measure was major molecular response (MMR) at 24 weeks. The MMR rate was 25% (95% CI = 19, 33) in patients treated with asciminib compared with 13% (95% CI = 6.5, 23; p = 0.029) in those receiving bosutinib. With a median duration of follow-up of 20 months, the median duration of MMR has not yet been reached.
A mult-center, open-label clinical trial (CABL001X2101; NCT02081378) evaluated asciminib in patients with Ph+ CML in CP with the T315I variation. Efficacy was based on 45 patients with the T315I mutation who received asciminib 200 mg twice daily. Patients continued treatment until they experienced unacceptable toxicity or treatment failure. The main efficacy outcome measure was MMR, which was achieved by 24 weeks in 42% (n = 19, 95% CI = 28%–58%) of the patients and by 96 weeks in 49% (n = 22, 95% CI: 34%–64%) of the patients. The median duration of treatment was 108 weeks (range = 2–215 weeks).
The most common adverse reactions reported in 20% or more of patients are upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities are decreased platelet counts, neutrophil counts, and hemoglobin and increased triglycerides, creatine kinase, alanine aminotransferase, lipase, and amylase.
The recommended asciminib dose in patients with Ph+ CML in CP, previously treated with two or more TKIs, is 80 mg taken orally once daily at approximately the same time each day or 40 mg twice daily at approximately 12-hour intervals. The recommended asciminib dose in patients with Ph+ CML in CP with the T315I variation is 200 mg taken orally twice daily at approximately 12-hour intervals.
The review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application four months ahead of the goal date.
FDA granted the application priority review, breakthrough designation, fast track designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.