SWITZERLAND – In a significant advancement for chronic myeloid leukemia (CML) care, Novartis’ Scemblix has now gained accelerated approval from the U.S. Food and Drug Administration (FDA).
This approval allows Scemblix to be used as an initial treatment option for patients diagnosed with Philadelphia chromosome-positive (Ph+) chronic-phase CML, opening new pathways in first-line treatment for this patient group.
Scemblix’s approval as a first-line treatment reflects its strong potential to address unmet needs in CML care, positioning it as a successor to Novartis’ Gleevec—a cornerstone in CML therapy for over two decades.
Approved in 2021 for third-line treatment, Scemblix’s reach is now expanded to the first-line CML setting.
“We see this as an important step toward fulfilling our goal of expanding treatment options for patients, especially in the underserved first-line CML space,” stated Victor Bulto, President of Novartis U.S.
Initially designed to serve third-line patients, only about 15% of CML cases, Scemblix now holds promise to reach the much larger first-line patient population.
Scemblix vs. Standard CML Therapies
Scemblix (asciminib) demonstrated notable efficacy in the phase 3 ASC4FIRST trial, which enrolled 405 newly diagnosed patients.
Compared to a selection of standard treatments, Scemblix achieved a major molecular response (MMR) at 48 weeks in 67.7% of patients, a significant improvement over the 49% response rate in the control group.
Notably, in comparison with imatinib—the standard first-line TKI—Scemblix achieved a 69.3% MMR response, compared to 40.2% for imatinib.
Bulto elaborated on this shift, emphasizing that Scemblix’s distinctive mechanism targets the ABL myristoyl pocket, which is unique compared to the ATP-binding sites of other tyrosine kinase inhibitors (TKIs).
“Scemblix stands out for its novel mechanism of action, offering a differentiated approach to targeting leukemia,” he said, noting that this distinction is expected to drive adoption among healthcare providers who currently favor imatinib.
Addressing challenges in the first-line market
Despite Scemblix’s effectiveness, Bulto acknowledged potential obstacles in transitioning patients from well-established treatments such as Gleevec and Tasigna.
“There’s a number of physicians who are very comfortable with Gleevec’s tolerability and safety, especially after so many years of use,” he shared, noting that Gleevec’s 2023 sales of US $561 million underscore its enduring position in CML care.
Scemblix’s arrival will likely be gradual, as many doctors may continue to prescribe Gleevec or its generic versions due to familiarity and comfort with its tolerability.
Long-term safety and patent protection
The safety profile of Scemblix was a critical factor in its FDA approval, as the trial data revealed fewer serious adverse events compared to other TKIs.
Discontinuation due to adverse events was 4.5% with Scemblix, lower than the 11.1% for Gleevec and 9.8% for other second-generation TKIs.
However, experts, including Dr. Vinay Prasad of UCSF, in a journal urge caution, highlighting the need for more data on overall survival outcomes.
“Without clear overall survival benefit, the need for ongoing research remains crucial,” Dr. Prasad pointed out, suggesting a prudent approach to implementing new therapies with limited survival data.
Novartis anticipates continued growth for Scemblix, bolstered by patent protection through the mid-2030s.
In addition, due to its orphan drug status, Scemblix will not be subject to Inflation Reduction Act price controls—a factor that may support its sustained market viability.
