Novartis has secured accelerated approval from the U.S. Food and Drug Administration (FDA) for Scemblix (asciminib) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase (Ph+ CML-CP). This approval marks a significant advancement in the CML treatment landscape, providing a new therapeutic option for patients.
Scemblix is a "specifically targeting the ABL myristoyl pocket" (STAMP) inhibitor. It is the first CML therapy to demonstrate both efficacy and a favorable tolerability and safety profile when compared to imatinib and second-generation tyrosine kinase inhibitors (TKIs).
The FDA's accelerated approval is grounded in the major molecular response (MMR) rate at week 48 observed in the Phase III ASC4FIRST trial. This head-to-head, multi-center, open-label, randomized study compared once-daily 80mg Scemblix to investigator-selected standard-of-care TKIs in 405 adults with Ph+ CML-CP.
Victor Bulto, President of Novartis US, emphasized the importance of new treatment options, stating, "Despite many advances in the field, patients still need treatment options that are highly effective with a favorable tolerability profile to help enable them to achieve meaningful outcomes as they manage chronic conditions."
ASC4FIRST Trial Results
The ASC4FIRST trial demonstrated that Scemblix achieved superior MMR rates at week 48 compared to standard-of-care TKIs and imatinib alone. Specifically, 20% more subjects who received Scemblix achieved MMR compared to those on investigator-selected standard-of-care TKIs, and 30% more achieved MMR compared to imatinib alone at week 48.
Patients treated with Scemblix also achieved deeper rates of molecular responses, including MR4, compared to those treated with investigator-selected TKIs and imatinib alone by week 48.
Supporting Data
The approval was also supported by preliminary data from the Phase II ASC2ESCALATE study, which included patients previously treated with one prior TKI.
Implications of Approval
This expanded indication significantly increases the eligible population for Scemblix, including both newly diagnosed and previously treated adult patients, potentially quadrupling the number of patients who could benefit from this therapy.
It is important to note that full approval for this new indication may depend on the verification and description of clinical benefit from confirmatory evidence. The ASC4FIRST trial is ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint and additional secondary endpoints.
