On October 29, 2021, the FDA approved Scemblix (asciminib; from Novartis AG), an oral kinase inhibitor, for the treatment of (1) patients with chronic-phase Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) after ≥2 tyrosine kinase inhibitors (TKIs), and for (2) adults with chronic-phase Ph-positive CML and T315I mutation. Scemblix is the first FDA approval of a drug for CML that is a Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor. This new type of STAMP drug may offer an improvement over other therapies for some patients with these types of CML.
The FDA approved these 2 indications based on results from 2 clinical trials. The first study was a multicenter, randomized, active-controlled, open-label clinical trial of 233 patients with chronic-phase Ph-positive CML who previously received 2 or more TKIs. Patients were stratified according to major cytogenetic response to Scemblix tablets twice daily or to Bosulif (bosutinib) once daily, until unacceptable side effects or treatment failure.
After 24 weeks, the major molecular response rate was 25% with Scemblix compared with only 13% with Bosulif. At an average of 20 months of follow-up, the average duration of response has not been reached (meaning many patients were still responding).
The second study was a multicenter, open-label study that included 45 patients with chronic-phase Ph-positive CML and T315I mutation. All patients received Scemblix twice daily until unacceptable side effects or treatment failure. At 24 weeks, 42% of the patients had a major molecular response to Scemblix. By 96 weeks, that rate was increased to 49%. The average duration of treatment was 108 weeks (range, 2-215 weeks).
The most common side effects with Scemblix were upper respiratory tract infection, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities were reduced platelet counts, increased triglycerides, decreased neutrophil counts and hemoglobin, and increased creatine kinase, alanine aminotransferase, lipase, and amylase.