Novartis announced that Scemblix (asciminib) has received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). This approval marks a significant advancement in CML treatment, offering a new first-line option with demonstrated superior efficacy and a favorable safety profile compared to existing standard of care (SoC) therapies.
The FDA's decision was based on data from the Phase III ASC4FIRST trial, which compared once-daily Scemblix to investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib, and bosutinib). The study's primary endpoint was the major molecular response rate (MMR) at week 48. Scemblix demonstrated significantly higher MMR rates compared to both investigator-selected SoC TKIs and imatinib alone.
Superior Efficacy and Safety Profile
The ASC4FIRST trial revealed that nearly 20% more patients treated with Scemblix achieved MMR compared to those on investigator-selected SoC TKIs (68% vs. 49%, p < 0.001). Furthermore, almost 30% more patients achieved MMR with Scemblix compared to imatinib alone (69% vs. 40%, p < 0.001) at week 48. Scemblix also demonstrated a favorable safety and tolerability profile, with fewer treatment-related grade ≥3 adverse reactions (25.5% vs. 33% and 42%), 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%) compared to imatinib and second-generation TKIs.
"Many patients who are newly diagnosed with CML struggle to navigate this chronic condition and may switch or even stop treatment because of side effects that interrupt their daily lives," said Lee Greenberger, Ph.D., Chief Scientific Officer at The Leukemia & Lymphoma Society. "That’s why approvals of new first-line treatment options are so important. 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."
Addressing Unmet Needs in CML Treatment
While TKIs have transformed CML into a manageable chronic disease, challenges related to efficacy and safety persist, hindering long-term treatment success for many patients. Approximately half of CML patients do not achieve efficacy milestones (MMR), and nearly one in four discontinue or switch treatment within the first year. Scemblix offers a potential solution by providing a highly effective treatment option with improved tolerability.
"While there are a range of effective TKIs currently available for newly diagnosed patients, clinicians frequently have had to weigh sacrificing either efficacy or tolerability," said Jorge Cortes, M.D., Director, Georgia Cancer Center. "In the first-of-its-kind ASC4FIRST trial, Scemblix achieved impressive results across all three parameters of efficacy, safety and tolerability versus all standard of care TKIs. This Scemblix data has the potential to be practice-changing."
Novel Mechanism of Action
Scemblix (asciminib) is the first CML treatment that functions by Specifically Targeting the ABL Myristoyl Pocket (STAMP inhibitor). This mechanism differs from current CML treatments, which are TKIs that target the ATP-binding site. This novel approach may contribute to its improved efficacy and safety profile.
Ongoing Studies and Future Directions
The ASC4FIRST 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. Furthermore, Scemblix is being investigated across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination.
