The U.S. Food and Drug Administration (FDA) has granted accelerated approval to the BCR::ABL1 kinase inhibitor asciminib (Scemblix) for adult patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (Ph-positive CML) in chronic phase. The FDA approval was granted on October 29, 2024.
Asciminib is a first-in-class specific allosteric inhibitor of BCR::ABL1 that selectively binds to a myristoyl pocket. This action leads to conformational changes induced by myristate-binding to the N-terminus of ABL1.
Efficacy and Safety
The efficacy of asciminib for newly diagnosed Ph-positive CML in chronic phase was evaluated in ASC4FIRST (ClinicalTrials.gov identifier NCT04971226), a multicenter, randomized, active-controlled, open-label trial. A total of 405 patients were randomly assigned (1:1) to receive either asciminib or investigator-selected tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, or bosutinib).
The main efficacy outcome measure was major molecular response (MMR) rate at 48 weeks. The MMR rate at 48 weeks was 68% (95% confidence interval [CI] = 61%–74%) in the asciminib arm and 49% (95% CI = 42%–56%) in the investigator-selected tyrosine kinase inhibitors arm (difference = 19% [95% CI = 10%–28%], P < .001). Within the imatinib stratum, the MMR rate was 69% (95% CI = 59%–78%) in the asciminib arm and 40% (95% CI = 31%–50%) in the investigator-selected tyrosine kinase inhibitors arm (difference = 30% [95% CI = 17%–42%], P < .001).
In the pooled safety population in patients with newly diagnosed and previously treated Ph-positive CML in chronic phase, the most common adverse reactions (≥ 20%) were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea. The most common laboratory abnormalities (≥ 40%) in patients with newly diagnosed Ph-positive CML in chronic phase were decreased lymphocyte count, decreased leukocyte count, decreased platelet count, decreased neutrophil count, and decreased calcium corrected.
The recommended asciminib dosage is 80 mg taken orally once daily at approximately the same time of day or 40 mg taken orally twice daily at approximately 12-hour intervals.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. For this review, the FDA collaborated with Health Canada and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
Expedited Programs
This 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 the FDA’s assessment. The application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation and was approved 1 month ahead of the goal date.
