FDA Accelerates Approval of Aceminib for Adult Patients with Newly Diagnosed Ph+CML-CP

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Asciminib (Scemblix; Novartis) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+CML-CP) in the chronic phase. The accelerated approval was based on data from the Phase 3 clinical trial ASC4FIRST (NCT04971226), in which aximinib performed better than other investigator's choice (IS) standard of care (SoC) tyrosine kinase inhibitors (TKIs) and imatinib (Gleevec) at 48 weeks.

Asiminib is the first CML treatment that works by specifically targetingthe myristoyl pocket of ABL. In the United States, it is approved for the treatment of newly diagnosed adults and is also approved for the treatment of adults with previously treated Ph+ CML-CP. In addition, aceminib was granted Breakthrough Therapy designation and prioritized review for the treatment of patients with newly diagnosed Ph+ CML-CP. Many patients newly diagnosed with chronic myelogenous leukemia have difficulty adjusting to this chronic disease and may experience interruptions in daily life or even discontinuation of treatment due to side effects. This is why approval of new first-line treatment options is so important. For patients, finding a drug that works for them during the initial stages of treatment may lead to better long-term disease control with fewer side effects.

The ASC4FIRST (NCT04971226) trial is an ongoing head-to-head, multicenter, open-label, randomized Phase 3 trial investigating oral aceminib versus an investigator's choice of SoC The TKIs inhibitors imatinib, nilotinib (Tasigna), dasatinib (Sprycel; Bristol-Myers Squibb), and bosutinib (Bosulif; Pfizer)—in adults with newly diagnosed Ph+ CML-CP. A total of 405 patients were randomly assigned to receive aximinib 80 mg orally once daily, imatinib 400 mg orally once daily with food, nilotinib 300 mg orally twice daily on an empty stomach, dasatinib 100 mg orally once daily with or without food, or bosutinib 400 mg orally once daily.

The primary endpoint of the study isMMR measured at 48 weeks. Secondary endpoints measured at 96 weeks included MMR and time to study discontinuation due to adverse events (AEs), and endpoints assessed at 5 years of follow-up included failure-free survival, event-free survival, progression-free survival, and overall survival.

Based onAt 48 weeks, nearly 20% more patients achieved MMR in patients treated with aximinib (68%) compared with those treated with SoC TKI (49%), and approximately 30% more patients achieved MMR compared with patients treated with imatinib alone (69% vs. 40%; p<0.001). In addition, compared with imatinib and other second-generation TKIs, aximinib is also the first treatment option for CML, showing superior efficacy and good safety and tolerability. At week 48.1, patients receiving aximinib had a higher incidence of MMR, including MR4, compared with patients receiving TKIs and imatinib alone (41% vs. 22% and 16%).

The most commonAEs include musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea. Patients treated with aximinib also reported fewer treatment-related grade 3 or higher AEs (25.5%), dose reductions (6%), and halved the incidence of AEs leading to treatment discontinuation (4.5%) compared with imatinib alone (33%, 14%, and 11%, respectively) and second-generation TKIs (42%, 24%, and 9.8%, respectively). In newly diagnosed patients, safety was consistent with previous studies, and investigators observed no new safety concerns.

Although there is currently a range of effectiveTKIs available for use in newly diagnosed patients, clinicians often have to weigh the trade-off of sacrificing efficacy or tolerability. In the first-of-its-kind ASC4FIRST trial, [aceminib] achieved impressive results across three parameters: efficacy, safety and tolerability compared with all standard-of-care TKIs. These data from Assimini have the potential to change practice.