On October 29, 2024, the Food and Drug Administration granted accelerated approval to asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP).
Full prescribing information for Scemblix will be posted on Drugs@FDA.
Efficacy and Safety
The efficacy of asciminib for newly diagnosed Ph+ CML in CP was evaluated in ASC4FIRST (NCT04971226), a multicenter, randomized, active-controlled, open-label trial. A total of 405 patients were randomized (1:1) to receive either asciminib or investigator-selected tyrosine kinase inhibitors (IS-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% CI: 61, 74) in the asciminib arm and 49% (95% CI: 42, 56) in the IS-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 IS-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 Ph+ CML in CP, 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+ CML in CP 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. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada (HC) and Switzerland’s Swissmedic (SMC). The application reviews are ongoing at the other regulatory agencies.
Expedited Programs
This review used the Real-Time Oncology Review (RTOR) 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 FDA approved this application one month ahead of the FDA goal date.
This application was granted priority review, breakthrough designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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 or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email [email protected].
Follow the Oncology Center of Excellence on X: @FDAOncology.
