ASCO: Novartis' Scemblix outperforms Gleevec in newly diagnosed leukemia

Novartis has developed Scemblix, a new treatment for chronic myeloid leukemia (CML), aiming to improve safety and tolerance compared to existing tyrosine kinase inhibitors (TKIs). Results from a head-to-head study comparing Scemblix with Novartis' standard TKI, Gleevec, suggest a favorable alternative for newly diagnosed patients.

The ASC4FIRST study is the first randomized phase 3 trial to compare Scemblix directly with Gleevec or a stronger second-generation TKI in recently diagnosed CML patients. Novartis announced the results at the American Society of Clinical Oncologist (ASCO) annual conference, following a primary analysis released in January.

Involving 405 patients, the trial assessed molecular response rates (MRRs). At 48 weeks, 68% of patients on Scemblix achieved MRR, compared to 49% of those using older TKIs. Scemblix also outperformed in deep molecular response rates, with 39% of patients achieving this level compared to 21% in the TKI group.

Dr. Timothy Hughes of the South Australian Health and Medical Research Institute and the University of Adelaide, Australia, highlighted the potential for Scemblix to enable more patients to achieve treatment-free remission, the ultimate goal of CML therapy.

Molecular response rates, especially deep molecular responses, could provide insights into potential treatment-free remission. This measure is more sensitive than traditional tumor response rate endpoints and evaluates the presence of BCR-ABL1 in the blood. Scemblix initially earned conditional approval for third-line CML treatment based on MRR data three years ago.

While overall survival and progression-free survival are the gold standards for oncology treatments, deep molecular response and tolerability are crucial for chronic diseases like CML. The advent of Gleevec in 2001 significantly improved life expectancy for CML patients, making it comparable to the general population. It was the first approved TKI, paving the way for other drugs like AstraZeneca’s Tagrisso and transforming CML from a fatal diagnosis into a manageable condition.

However, traditional TKIs do not work effectively for all patients, posing challenges for long-term treatment due to the chronic nature of CML. Adverse events and drug intolerance often lead to therapy discontinuation, with up to 25% of patients stopping treatment within five years. Scemblix was designed to address these issues, showing fewer adverse events in the study. The most common side effects for Scemblix were low platelet and neutrophil counts, at 13% and 10%, respectively.

Moreover, only 1% of patients on Scemblix experienced severe side effects like blood clots. Importantly, the study showed a lower rate of treatment discontinuation and fewer dose adjustments or interruptions for Scemblix.

If Scemblix becomes a first-line treatment, it could potentially benefit the estimated 9,280 new CML patients diagnosed annually. However, Novartis CEO Vas Narasimhan acknowledged that Gleevec’s long-standing market presence might make some doctors hesitant to switch to the new drug. Nevertheless, he anticipates rapid adoption among patients currently on second-generation TKIs, who are more open to new treatments.

Researchers will continue to monitor ASC4FIRST participants to evaluate Scemblix’s long-term safety and determine if early MMR achievement predicts better outcomes. Further analyses will focus on overall survival, progression-free survival, and treatment-free remission. As of late November, 86% of Scemblix-treated patients were continuing their treatment.