January 08, 2023
Novartis' Scemblix Excels in Phase III Trial, Significantly Outperforming Standard-of-Care TKIs in Newly Diagnosed CML Patients
Novartis has reported promising outcomes from the primary analysis of ASC4FIRST, a pivotal Phase III trial investigating Scemblix (asciminib) against investigator-chosen tyrosine kinase inhibitor (TKI) treatments for newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). The ASC4FIRST trial, the first of its kind, compares a CML treatment head-to-head with approved standard-of-care first- and second-generation TKIs.
In this Phase III trial, Scemblix exhibited superior major molecular response (MMR) rates at week 48 compared to standard-of-care TKIs (imatinib, nilotinib, dasatinib, and bosutinib) in newly diagnosed Ph+CML-CP patients. The trial met both primary endpoints, demonstrating clinically meaningful and statistically significant results for MMR rates for Scemblix compared to investigator-selected TKIs and compared to imatinib.
The safety and tolerability profile of Scemblix were favorable, showcasing fewer adverse events (AEs) and treatment discontinuations in comparison to investigator-selected standard-of-care TKIs. Notably, no new safety signals were identified, aligning with the established safety profile of Scemblix.
Current standard-of-care TKIs see more than 60% of newly diagnosed CML patients failing to achieve molecular response goals within the first year of treatment. Intolerance and adverse events frequently lead to discontinuation of TKI therapy, with discontinuation rates due to AEs reaching up to 25% within five years.
The ASC4FIRST trial highlights the potential of Scemblix to address these challenges, offering improved MMR rates and a more favorable safety profile compared to standard-of-care TKIs. The findings underscore the significance of continued advancements in CML treatment, aiming to transform the condition into a manageable chronic disease with a life expectancy similar to that of the general population. Tolerability remains a crucial treatment goal, acknowledging the impact of intolerance and adverse events on patient outcomes.