Novartis Reports Strong Three-Year Scemblix Results in Newly Diagnosed CML

Novartis reported positive 144-week results from the Phase 3 ASC4FIRST trial showing that Scemblix® (asciminib) continued to widen its efficacy advantage over standard tyrosine kinase inhibitors (TKIs), including second-generation TKIs, in adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Presented at the 2026 ASCO Annual Meeting, the findings provide further evidence of durable disease control with long-term treatment.

Superior Molecular Responses

At week 144, Scemblix achieved a major molecular response (MMR) rate of 77.1% compared with 53.4% for investigator-selected standard-of-care TKIs, including imatinib, nilotinib, dasatinib, and bosutinib.

In the imatinib subgroup, MMR rates reached 79.2% versus 47.1%. Notably, Scemblix also outperformed second-generation TKIs, achieving an MMR rate of 75.0% compared with 59.8%, representing a clinically meaningful 15.2% advantage.

Patients receiving Scemblix achieved deeper molecular responses, with MR4 rates of 55.7% versus 36.3% and MR4.5 rates of 42.3% versus 24.5% for standard TKIs. More patients also remained on treatment at week 144 compared with standard therapy (78.6% vs. 55.9%), supporting sustained efficacy and treatment persistence.

Improved Tolerability and Safety

Safety findings remained consistent with previous analyses, and no new safety signals emerged.

Grade ≥3 adverse events occurred in 49% of patients receiving Scemblix, compared with 52% for imatinib and 63% for second-generation TKIs. Discontinuations due to adverse events were substantially lower with asciminib at 6%, versus 13% and 14%, respectively. Scemblix also required fewer dose modifications and treatment interruptions related to adverse events.

The most common adverse events included diarrhea, headache, fatigue, musculoskeletal pain, and rash.

Novel Mechanism of Action

Scemblix is the first CML therapy to specifically target the ABL myristoyl pocket through its STAMP (Specifically Targeting the ABL Myristoyl Pocket) mechanism. Unlike conventional TKIs that inhibit the ATP-binding site of BCR-ABL1, asciminib acts through a distinct pathway that may contribute to its differentiated efficacy and tolerability profile.

Regulatory and Strategic Positioning

The latest ASC4FIRST findings strengthen the evidence supporting frontline use of Scemblix and may influence future treatment guidelines, physician adoption, and global market uptake. The growing efficacy advantage over both first- and second-generation TKIs positions asciminib as a strong contender to reshape frontline treatment expectations in CML.

Patient Impact and Long-Term Outlook

Because many patients with CML remain on therapy for years or decades, long-term tolerability is critical. The low discontinuation rate observed with Scemblix suggests more patients may be able to maintain therapy and sustain deep molecular responses over time.

Expert Commentary and Next Steps

Jorge Cortes, MD, Chief of Hematology at the UAB O’Neal Cancer Center, said the widening efficacy advantage observed over nearly three years highlights asciminib’s ability to deliver durable disease control while maintaining a favorable safety profile.

The ASC4FIRST study remains ongoing, with additional efficacy and safety follow-up planned. Novartis will also present the 144-week findings at the European Hematology Association (EHA) 2026 Congress as longer-term data continue to mature.

Reference

Scemblix® continued to show superior efficacy and favorable safety and tolerability profile at week 144 in newly diagnosed CML | Novartis