Novartis study suggests expanded role for targeted leukemia drug

Patients suffering from chronic myeloid leukemia (CML), a persistent bone marrow cancer, typically receive treatment with targeted medications that have significantly extended survival rates over the past twenty years. Recently released study findings suggest that Scemblix, the latest of these therapies, may offer improved safety and effectiveness, potentially becoming a preferred initial treatment option. These results stem from a late-stage clinical trial conducted by Scemblix's manufacturer, Novartis, and will be highlighted at the American Society of Clinical Oncology's (ASCO) annual conference.

The clinical trial, named ASC4FIRST, demonstrated that Scemblix induced treatment responses in a higher percentage of participants compared to other targeted medications, including the commonly used Gleevec and newer drugs. Furthermore, patients treated with Scemblix experienced a deep molecular response, which could eventually signify remission and allow for discontinuation of treatment. The researchers noted that Scemblix showed significantly better safety and tolerability compared to Gleevec and other kinase inhibitors.

The combination of effectiveness and safety in Scemblix may enable more patients to achieve treatment-free remission, the ultimate goal in CML therapy, according to Timothy Hughes, the lead author of the study and an oncologist at the University of Adelaide, Australia. Scemblix is already approved in the U.S. and other countries for CML that has been treated with at least two other kinase inhibitors. Based on the success of the ASC4FIRST trial, Novartis has applied for U.S. approval for Scemblix as a treatment for newly diagnosed CML patients.

Should Scemblix receive first-line approval, it would join Gleevec and three additional kinase inhibitors already available for initial CML treatment. The introduction of these therapies in the 2000s and 2010s has significantly improved the five-year survival rate for CML, increasing it to around 70% for diagnoses made between 2012 and 2018. However, patients often need to switch therapies due to cancer resistance or intolerable side effects.

According to Oreofe Odejide, a medical oncologist at the Dana-Farber Cancer Institute, a substantial number of CML patients must remain on long-term treatment, and over 40% of newly diagnosed patients do not achieve a major molecular response after a year of therapy. Some patients must change treatments due to adverse effects.

The recent findings suggest that Scemblix could address both resistance and tolerability issues. Unlike previous kinase inhibitors, Scemblix targets a specific pocket on a mutant protein that drives CML, potentially making it more selective and less toxic. Jorge Cortes, director of the Georgia Cancer Center and an investigator in the ASC4FIRST study, noted that Scemblix’s unique mechanism might contribute to its improved safety profile.

In the ASC4FIRST trial, more than 400 adults with newly diagnosed CML were randomized to receive either Scemblix or another selected kinase inhibitor. After 48 weeks, 68% of patients treated with Scemblix achieved a major molecular response compared to 49% of those on other kinase inhibitors. This response is measured by the level of mutant protein in the body, with major molecular response indicating levels at or below 0.1% on an International Scale. This metric is a strong predictor of long-term deep molecular responses, which can eventually allow for treatment discontinuation.

Nearly 40% of patients treated with Scemblix met the criteria for deep molecular responses, compared to 21% of those on other kinase inhibitors. The trial was designed to compare Scemblix to either Gleevec or second-generation kinase inhibitors, depending on participants’ profiles. Scemblix showed superior results in both groups, particularly among patients selected for Gleevec.

Overall, Scemblix was associated with lower rates of study discontinuation, dose adjustments, and treatment interruptions, as well as fewer significant side effects compared to other kinase inhibitors. The most common side effects included low platelet and neutrophil counts. 

Novartis aims to make Scemblix the leading CML treatment globally, according to CEO Vas Narasimhan. The company plans to continue monitoring patients for longer-term outcomes and to conduct additional studies on progression-free and overall survival.

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