FDA Grants Accelerated Approval to Novartis' Scemblix for Newly Diagnosed CML
Key Insights
The FDA granted accelerated approval to Scemblix (asciminib) for adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (search) in chronic phase (Ph+ CML (search)-CP).
Approval was based on the ASC4FIRST Phase III trial, which showed Scemblix had superior major molecular response (MMR) rates at week 48 compared to standard of care tyrosine kinase inhibitors (TKIs).
Scemblix is the first CML (search) treatment to demonstrate superior efficacy and a favorable safety profile versus imatinib and second-generation TKIs in newly diagnosed patients.
Novartis announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to Scemblix (asciminib) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (search) in chronic phase (Ph+ CML (search)-CP). This decision expands the treatment options for newly diagnosed CML patients, offering a therapy that has demonstrated superior efficacy and a favorable safety profile compared to existing standard of care treatments. The accelerated approval is based on data from the Phase III ASC4FIRST trial.
Superior Efficacy and Safety Profile
The approval of Scemblix is rooted in the ASC4FIRST Phase III trial, a head-to-head comparison of once-daily Scemblix against investigator-selected standard of care (SoC) tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, dasatinib, and bosutinib. The trial's results demonstrated that Scemblix achieved significantly higher major molecular response (MMR) rates at week 48 compared to both investigator-selected SoC TKIs (68% vs. 49%, p < 0.001) and imatinib alone (69% vs. 40%, p < 0.001).
Scemblix also distinguished itself as the first CML (search) treatment to show superior efficacy alongside a more favorable safety and tolerability profile compared to imatinib and second-generation TKIs. The incidence of treatment-related Grade ≥3 adverse reactions was lower with Scemblix (25.5%) compared to SoC TKIs (33% and 42%). Additionally, Scemblix resulted in fewer dose reductions (6% vs. 14% and 24%) and a lower rate of adverse reactions leading to treatment discontinuation (4.5% vs. 11% and 9.8%).
Patients treated with Scemblix also achieved deeper molecular responses, including MR4 rates of 41% compared to 22% for investigator-selected TKIs and 16% for imatinib alone by week 48.
Clinical Significance and Patient Impact
The expanded indication for Scemblix in Ph+ CML (search)-CP significantly increases the eligible patient population, providing newly diagnosed adults access to a treatment that has demonstrated superior efficacy and a favorable safety and tolerability profile. According to Lee Greenberger, Ph.D., Chief Scientific Officer at The Leukemia & Lymphoma Society, "For patients, finding a medicine that’s right for them at the very beginning of treatment may lead to better long-term disease control with fewer side effects."
Despite the effectiveness of existing TKIs, challenges persist in achieving long-term treatment success. Many newly diagnosed patients do not meet molecular response goals, and a significant number discontinue or switch treatments due to intolerance. Data indicates that nearly half of CML (search) patients do not achieve MMR, and almost one in four discontinue or switch treatment within the first year.
The ASC4FIRST Trial Details
The ASC4FIRST trial (NCT04971226) is a Phase III, multi-center, open-label, randomized study comparing oral Scemblix 80 mg QD to investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib, or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML (search)-CP. The primary endpoints of the study are the comparison of efficacy of asciminib vs. investigator-selected SoC TKIs and the comparison of efficacy vs. imatinib alone, based on the proportion of patients achieving MMR at week 48.
The trial is ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints.
About Scemblix (asciminib)
Scemblix is the first CML (search) treatment that functions as a Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor. It has received approval in over 75 countries, including the EU, for patients previously treated with two or more TKIs with Ph+ CML-CP. In some countries, including the US, Scemblix is also approved for patients with Ph+ CML-CP with the T315I mutation. It is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination.