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 leukaemia (Ph+ CML) in chronic phase (CP).

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 diarrhoea. 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.

Source: FDA