Novartis Scemblix® Phase III data shows superior efficacy and safety in newly diagnosed CML

Novartis recently announced significant findings from the Phase III ASC4FIRST trial, presented at the 2024 American Society of Clinical Oncology (ASCO) meeting. The study evaluated Scemblix® (asciminib) against various standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP).

Scemblix showed superior major molecular response (MMR) rates at week 48 compared to investigator-selected SoC TKIs, including imatinib, nilotinib, dasatinib, and bosutinib, as well as imatinib alone. Specifically, Scemblix achieved MMR rates of 67.7% against 49.0% with SoC TKIs and 69.3% against 40.2% with imatinib alone. These results were statistically significant and clinically meaningful.

Additionally, Scemblix demonstrated a favorable safety profile. It resulted in fewer grade ≥3 adverse events (AEs), fewer dose adjustments, and half the rate of AEs leading to treatment discontinuation compared to both imatinib and second-generation (2G) TKIs. The safety data indicated 38% of patients on Scemblix experienced grade ≥3 AEs, in contrast to 44% and 55% for imatinib and 2G TKIs, respectively. Scemblix also had a lower discontinuation rate due to AEs, recorded at 5% versus 11% for imatinib and 10% for 2G TKIs.

Professor Tim Hughes, MD, from the South Australian Health & Medical Research Institute (SAHMRI), emphasized the significance of these findings, noting that Scemblix is the first CML treatment to demonstrate significantly better efficacy compared to standard-of-care TKIs while also maintaining an excellent safety and tolerability profile. He highlighted the potential of Scemblix as a promising frontline option for achieving treatment goals in newly diagnosed patients.

The ASC4FIRST trial had a median follow-up of 16.3 months for Scemblix and 15.7 months for investigator-selected SoC TKIs. Notably, nearly 20% more patients treated with Scemblix achieved MMR at week 48 compared to SoC TKIs, and nearly 30% more achieved MMR compared to imatinib alone. Furthermore, patients on Scemblix reached deeper molecular responses (MR4 and MR4.5) compared to those on SoC TKIs and imatinib alone.

Scemblix was granted Breakthrough Therapy Designation by the US FDA, with its submission currently under review via the agency’s Oncology Center of Excellence Real-Time Oncology Review (RTOR) program. These data will also feature as a plenary presentation at the European Hematology Association (EHA) 2024 Congress.

In the ASC4FIRST Phase III trial, 405 adult patients with newly diagnosed Ph+ CML-CP were randomized to receive either oral Scemblix (80 mg QD) or one of the investigator-selected SoC TKIs. The study aimed to compare the efficacy of Scemblix against SoC TKIs based on the proportion of patients achieving MMR at week 48. The trial is ongoing, with the next analysis set for week 96 to evaluate further secondary endpoints and safety profiles.

Scemblix, a STAMP inhibitor, is currently approved in over 70 countries for treating adults with Ph+ CML-CP who have had previous treatments with two or more TKIs. In some regions, it is also approved for patients with the T315I mutation. The drug represents an important treatment option for patients experiencing resistance or intolerance after prior TKI therapies.

Novartis, with its long-standing commitment to chronic myeloid leukemia (CML), continues to pioneer innovative treatments in this field. Their collaboration with the Max Foundation has significantly impacted patient outcomes in low- and middle-income countries, underscoring their dedication to global health improvement.