FDA approves Novartis' Scemblix for leukaemia

Novartis has been granted accelerated approval by the US Food and Drug Administration (FDA) for Scemblix (asciminib) to treat adults newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukaemia in its chronic phase (Ph+ CML-CP). Scemblix stands out as a "STAMP" inhibitor, specifically targeting the ABL myristoyl pocket, and it is the first therapy for CML to demonstrate both efficacy and a favorable safety profile compared to imatinib and second-generation tyrosine kinase inhibitors (TKIs).

The FDA's decision to accelerate approval is grounded on the major molecular response rate (MMR) at week 48 from the Phase III ASC4FIRST trial. This trial was a head-to-head, multi-center, open-label, randomized study comparing once-daily 80mg Scemblix with other standard-of-care TKIs chosen by investigators. The trial involved 405 adults with Ph+ CML-CP.

Victor Bulto, President of Novartis US, emphasized that despite significant advancements in the field, there remains a need for highly effective treatments with favorable tolerability profiles that help patients achieve meaningful outcomes in managing chronic conditions.

The approval is also supported by preliminary data from the Phase II ASC2ESCALATE study, which evaluated patients who had previously been treated with one prior TKI. In the ASC4FIRST trial, Scemblix demonstrated superior MMR rates at week 48 compared to both standard-of-care TKIs and imatinib alone. Specifically, 20% more patients who received Scemblix achieved MMR compared to those on standard-of-care TKIs, and 30% more achieved MMR compared to those on imatinib alone by week 48. Additionally, patients treated with Scemblix achieved deeper molecular responses, such as MR4, compared to those treated with investigator-selected TKIs and imatinib by the same timeframe.

The expanded indication for Scemblix significantly broadens the eligible patient population, nearly quadrupling it to include both newly diagnosed and previously treated adult patients. The ASC4FIRST trial continues, with the next scheduled analysis at week 96, to evaluate the key secondary endpoint along with other additional secondary endpoints.

In July 2024, the FDA granted priority review for Scemblix in this indication, further underscoring the therapy's potential to address unmet medical needs in patients with Ph+ CML-CP. This expanded approval offers hope for better management of chronic myeloid leukaemia by providing a new treatment option that combines efficacy with a favorable safety profile.