Scemblix demonstrates sustained response rate in 48-week follow-up in patients with chronic myeloid leukemia.- Novartis

In this analysis, presented at the 63rd American Society of Hematology Annual Meeting & Exposition (ASH), the major molecular response (MMR) rate at 48 weeks was 29.3% for patients treated with Scemblix vs. 13.2% for patients in the Bosulif arm, which is consistent with a doubling of the efficacy at 24 weeks (25% vs. 13% [P=0.029]). The proportion of patients treated with Scemblix who experienced adverse reactions leading to discontinuation was more than three times lower than those in the Bosulif arm (7.1% vs. 25%).

Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket. This novel mechanism of action, also known in scientific literature as a STAMP inhibitor, can help address resistance to TKI therapy in patients with CML and overcome mutations at the defective BCR-ABL1 gene, which is associated with the over-production of leukemic cells. Scemblix continues to be studied across multiple lines of treatment for CML-CP.

In this updated analysis, responses were also durable, with 60 out of 62 patients on Scemblix maintaining MMR at time of their last assessment. Scemblix continued to deliver more favorable deep molecular responses (MRs) with MR and MR rates at 48 weeks of 10.8% and 7.6%, compared to 3.9% and 1.3% in patients treated with Bosulif, respectively. Additionally, the cumulative proportion of patients achieving a level of BCR-ABL1 less than 1% at 48 weeks – a predictor of better long-term outcomes in this heavily pretreated patient population – was higher in the Scemblix arm than in the Bosulif arm (50.8% vs 33.7%).

The most common reason for treatment discontinuation was lack of efficacy in 37 (23.6%) patients treated with Scemblix and 27 (35.5%) patients treated with Bosulif. Median duration of exposure was 15.4 months (range, 0.0–37.3 months) for Scemblix and 6.8 months (range, 0.2–34.3 months) for Bosulif. With a longer duration of exposure, the safety and tolerability profile remains consistent with the primary analysis of the ASCEMBL trial. The most common (incidence greater than 20%) adverse reactions reported in this analysis were thrombocytopenia (29.5%) and neutropenia (23.1%) in the Scemblix arm; and diarrhea (71.1%), nausea (46.1%), increased ALT (28.9%), vomiting (26.3%), rash (23.7%), increased AST (21.1%) and neutropenia (21.1%) in the Bosulif arm.

Scemblix received FDA approval in October 2021 and is currently available for physicians to prescribe to appropriate patients in the US. Scemblix is also being evaluated in studies across multiple treatment lines and indications for CML-CP, including the ASC4FIRST Phase III study for newly diagnosed adult patients, as well as in a Phase Ib/II dose assessment study in pediatric patients with Ph+ CML-CP. Trial-in-progress posters for both are being presented at ASH.

Scemblix represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies , and it is being studied across multiple treatment lines for CML-CP. Specifically, the ASC4FIRST Phase III study (NCT04971226) evaluates Scemblix as a first-line treatment and is in the recruitment phase.