Novartis has received US Food and Drug Administration (FDA) accelerated approval for Scemblix (asciminib) to treat adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in its chronic phase (Ph+ CML-CP).
Scemblix, a "specifically targeting the ABL myristoyl pocket" (STAMP) inhibitor, is the first CML therapy to demonstrate efficacy along with a favourable tolerability and safety profile in comparison with imatinib and second-generation tyrosine kinase inhibitors (TKIs).
The FDA’s accelerated approval is based on the major molecular response rate (MMR) at week 48 from the Phase III, head-to-head, multi-centre, open-label, randomised ASC4FIRST trial.
The study compared once-daily 80mg Scemblix to all other investigator-selected standard-of-care TKIs in 405 adults with Ph+ CML-CP.
Novartis US president Victor Bulto stated: “Despite many advances in the field, patients still need treatment options that are highly effective with a favourable tolerability profile to help enable them to achieve meaningful outcomes as they manage chronic conditions.”
The approval was also backed by preliminary data from the Phase II ASC2ESCALATE study, which includes patients previously treated with one prior TKI.
In the ASC4FIRST trial, Scemblix showed superior MMR rates at week 48 compared to the standard of care TKIs and imatinib alone.
20% more subjects who received the therapy achieved MMR compared to investigator-selected standard-of-care TKIs, and 30% achieved MMR compared to imatinib alone at week 48.
Patients treated with Scemblix also achieved deeper rates of molecular responses, including MR4, against investigator-selected TKIs and imatinib alone by week 48.
Full approval for this new indication may depend on the verification as well as a description of clinical benefit from confirmatory evidence.
The expanded indication increases the eligible population for Scemblix by nearly four times, including newly diagnosed and previously treated adult patients.
The ASC4FIRST trial is ongoing and the next scheduled analysis will be at week 96 for evaluating the key secondary endpoint along with additional secondary endpoints.
In July 2024, the FDA granted priority review for the therapy in the given indication.
