The U.S. Food and Drug Administration (FDA) has granted accelerated approval to asciminib (Scemblix, Novartis) as a first-line treatment for adult patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia (CML). This approval marks a significant advancement in the treatment landscape for this rare blood cancer, offering a novel therapeutic option with improved efficacy and tolerability.
Asciminib, a tyrosine kinase inhibitor (TKI), was previously approved in 2021 for CML patients who had failed prior therapies. The recent approval expands its use to newly diagnosed patients, potentially benefiting a broader population. Novartis estimates that this approval quadruples the number of patients who can access this treatment.
Mechanism of Action
CML is characterized by the excessive production of abnormal white blood cells due to the activity of tyrosine kinase, driven by the Philadelphia chromosome. Asciminib uniquely inhibits the BCR-ABL protein, a product of the Philadelphia chromosome, at a different binding site compared to other TKIs. This distinct mechanism of action can overcome resistance and reduce off-target effects, leading to improved outcomes.
Clinical Trial Data
The FDA's approval was based on data from a Phase III clinical trial involving 405 newly diagnosed CML patients with Philadelphia chromosome. Patients were randomized to receive either asciminib or one of four other standard-of-care TKIs. The results demonstrated that asciminib was more effective, safer, and better tolerated than the comparator TKIs over a 48-week period. Common side effects observed with asciminib included muscle pain, rash, fatigue, respiratory infections, headaches, stomach pain, and diarrhea.
Jorge Cortes, MD, director of the Georgia Cancer Center, emphasized the potential impact of these findings, stating, "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."
Impact on Patient Care
Lee Greenberger, PhD, the chief scientific officer at The Leukemia & Lymphoma Society, highlighted the importance of finding well-tolerated treatments for newly diagnosed CML patients. "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," Greenberger said. "Finding a medicine that’s right for patients at the beginning of treatment may lead to better long-term disease control with fewer side effects."
Michael Mauro, MD, at Memorial Sloan Kettering Cancer Center (MSK), who co-led the early development of asciminib, believes that it will be different from other chronic myeloid leukemia treatments. “This drug works fantastically well,” he says. “Because it more frequently and more safely puts patients into what we call deep remission, after a period of time and with careful monitoring, they can consider stopping treatment completely.”
Ongoing Research
Novartis is continuing to evaluate asciminib in ongoing clinical trials to assess its long-term efficacy and safety. These trials will provide further insights into the potential for treatment-free remission and sustained disease control with asciminib.
