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Updated: Jun 18, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
FDA Approval Summary: Asciminib for Ph+ CML in Chronic Phase Treated with Two or More Tyrosine Kinase Inhibitors and
Gulsum E Pamuk1, Edwin C Y Chow1, Alexei C Ionan1
1Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Abstract:
On October 29, 2021, FDA granted accelerated approval to asciminib (SCEMBLIX; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% [95% confidence interval (CI), 30-46] in the asciminib arm versus 16% (95% CI, 8-26) in the bosutinib arm (P value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI, 34-64) in the single-arm CABL001X2101 study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, and increases in creatine kinase, alanine aminotransferase, aspartate aminotransferase, lipase, and amylase. This manuscript describes the basis for approval of these indications.
Insights
Asciminib, a tyrosine kinase inhibitor (TKI), received FDA approval for treating chronic myeloid leukemia (CML). It demonstrated significant molecular response rates in patients previously treated with other TKIs.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) is a challenging malignancy.
- Tyrosine kinase inhibitors (TKIs) have revolutionized CML treatment, but resistance and intolerance necessitate new therapeutic options.
Purpose of the Study:
- To detail the basis for the FDA's accelerated and traditional approvals of asciminib for adult Ph+ CML patients.
- To present efficacy and safety data supporting asciminib's use in CML treatment.
Main Methods:
- The ASCEMBL study: a randomized trial comparing asciminib with bosutinib in patients with Ph+ CML previously treated with two or more TKIs.
- The CABL001X2101 study: a single-arm trial evaluating asciminib in Ph+ CML patients with the T315I mutation.
Main Results:
- The first indication (previously treated patients) showed a significantly higher major molecular response (MMR) rate at 96 weeks for asciminib (38%) compared to bosutinib (16%).
- The second indication (T315I mutation) demonstrated an MMR rate of 49% by 96 weeks in the asciminib arm.
- Common adverse reactions included upper respiratory tract infections, musculoskeletal pain, and fatigue. Common laboratory abnormalities included thrombocytopenia, neutropenia, and anemia.
Conclusions:
- Asciminib provides a valuable new treatment option for adult patients with Ph+ CML.
- The drug is approved for CML patients who have failed prior TKI therapies and for those with the T315I mutation, based on robust efficacy and safety findings.
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