Asciminib Receives Accelerated Approval for Newly Diagnosed Chronic Myeloid Leukemia
Expert Perspectives · Keira Smith · 2024-10-31
The FDA has granted accelerated approval to asciminib (Scemblix®, Novartis) for adult patients with newly diagnosed, Philadelphia chromosome–positive chronic myeloid leukemia (Ph-positive CML) in chronic phase (CP).
Why Is the Approval of Asciminib Important?
“Patients with newly diagnosed CML need long-term therapy with high efficacy and safety,” wrote Andreas Hochhaus, MD, Professor of Internal Medicine, Hematology, and Oncology at the University Medical Center Jena in Germany, and colleagues, in their published results of the ASC4FIRST trial (NCT04971226) on which the approval was based. “Asciminib, a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket, may offer better efficacy and safety and few side effects than currently available frontline ATP-competitive tyrosine kinase inhibitors (TKIs).”
ASC4FIRST is the first study in newly diagnosed CML to compare all current standard-of-care frontline TKIs with a novel agent, asciminib.
Investigating Asciminib in ASC4FIRST
The multicenter, randomized, active-controlled, open-label, phase 3 trial enrolled 405 patients with PH-positive CML in CP. Patients were randomized 1:1 to receive either asciminib or investigators’ choice of tyrosine kinase inhibitor—imatinib, nilotinib, dasatinib, or bosutinib. The primary end point investigated with major molecular response rate at 48 weeks.
What They Found
At 48 weeks, asciminib produced a major molecular response rate of 68% compared with 49% in the investigator-selected TKI arm. In the prespecified imatinib stratum, the major molecular response rate was 69% in the asciminib arm versus 40% in the investigator-selected TKI arm.
Adverse Events
In the pooled safety population including patients with newly diagnosed and previously treated Ph-positive CML in CP, the most common adverse events (≥20%) with asciminib were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea. The most common laboratory abnormalities (≥40%) were decreased lymphocyte count, decreased leukocyte count, decreased platelet count, decreased neutrophil count, and decreased calcium corrected.
Putting It Into Context
“Asciminib is the only agent to show a statistically significant superior efficacy and excellent safety and tolerability versus all current standard-of-care frontline therapy, with potential to be the therapy of choice for CML,” concluded Timothy P. Hughes, MD, Clinical Professor of Medicine at the University of Adelaide, and colleagues, in their abstract presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
Dosing Instructions
The recommended dose of asciminib is 80 mg taken orally once daily at approximately the same time of day, or 40 mg taken orally twice daily at approximately 12-hour intervals.