On 29 October 2024, the US Food and Drug Administration (FDA) granted accelerated approval to asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase.
The efficacy of asciminib for newly diagnosed Philadelphia chromosome-positive CML in chronic phase was evaluated in ASC4FIRST (NCT04971226), a multicentre, randomised, active-controlled, open-label trial. A total of 405 patients were randomised (1:1) to receive either asciminib or investigator-selected tyrosine kinase inhibitors (TKIs) (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 TKIs arm (difference 19%, 95% CI 10, 28, p-value < 0.001). 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 TKIs arm (difference 30%, 95% CI 17, 42, p-value < 0.001).
In the pooled safety population in patients with newly diagnosed and previously treated Philadelphia chromosome-positive CML in chronic phase, the most common adverse reactions (≥20%) were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhoea. The most common laboratory abnormalities (≥40%) in patients with newly diagnosed Philadelphia chromosome-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’s Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada and Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review pilot programme, 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 FDA approved this application one month ahead of the FDA goal date.
This application was granted priority review, breakthrough designation, and orphan drug designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.