FDA Approves Scemblix (asciminib) for Chronic Myeloid Leukemia with Novel Mechanism
Key Insights
The FDA has approved Scemblix (asciminib) for Philadelphia chromosome-positive chronic myeloid leukemia (search) (Ph+ CML-CP) in adults after two or more tyrosine kinase inhibitors (TKIs (search)).
Scemblix demonstrated a significantly higher major molecular response (MMR) rate of 25% compared to bosutinib's 13% at 24 weeks in the Phase III ASCEMBL trial.
Scemblix is also approved for Ph+ CML-CP patients with the T315I mutation (search) and offers a novel mechanism of action as a STAMP inhibitor.
The U.S. Food and Drug Administration (FDA) has granted approval to Scemblix (asciminib) for the treatment of chronic myeloid leukemia (search) (CML) in adult patients. Specifically, Scemblix is indicated for Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) who have been previously treated with two or more tyrosine kinase inhibitors (TKIs (search)), and for patients with Ph+ CML-CP harboring the T315I mutation (search). This approval marks a significant advancement, offering a novel mechanism of action for patients who have developed resistance or intolerance to existing TKI therapies.
Clinical Efficacy and Safety
The FDA's decision was primarily based on the results of the Phase III ASCEMBL trial, which evaluated Scemblix in patients with Ph+ CML-CP resistant or intolerant to at least two prior TKIs (search). The trial demonstrated that Scemblix nearly doubled the major molecular response (MMR) rate compared to bosutinib at 24 weeks (25% vs. 13%, P=0.029). Furthermore, the proportion of patients discontinuing treatment due to adverse reactions was significantly lower in the Scemblix arm (7%) compared to the bosutinib arm (25%).
Novel Mechanism of Action
Scemblix functions as a STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor, binding to the ABL myristoyl pocket. This unique mechanism helps address resistance in CML patients previously treated with multiple TKIs (search) and overcome mutations at the BCR-ABL1 gene (search). Pre-clinical studies have also indicated that Scemblix has limited off-target activity.
Addressing Unmet Needs in CML Treatment
"CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both," said Dr. Michael J. Mauro, Hematologist and Myeloproliferative Neoplasms Program Leader at Memorial Sloan Kettering Cancer Center (MSK). He added, "The addition of Scemblix into the CML treatment landscape gives us a novel approach to combat this blood cancer, helping address clinical challenges in patients struggling after switching to a second treatment, as well as in patients who develop the T315I mutation (search) and face significantly worse outcomes."
Adverse Reactions
The most common adverse reactions (incidence ≥ 20%) observed in the Scemblix arm included upper respiratory tract infections and musculoskeletal pain. Common laboratory abnormalities included decreases in platelet and neutrophil counts, decreases in hemoglobin, and increases in triglycerides, creatine kinase, and alanine aminotransferase (ALT).
Ongoing Research
Novartis has initiated regulatory filings for Scemblix in multiple countries and regions globally. The ASC4FIRST Phase III study (NCT04971226) is currently evaluating Scemblix as a first-line treatment for CML-CP.