Scemblix Receives European Commission Approval for CML Treatment After TKI Failure
Key Insights
The European Commission has approved Scemblix (asciminib) for adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML-CP).
Scemblix is intended for patients previously treated with two or more tyrosine kinase inhibitors (TKIs) who have experienced resistance or intolerance.
Phase III ASCEMBL trial results showed Scemblix nearly doubled the major molecular response rate compared to bosutinib (25.5% vs. 13.2%) at 24 weeks.
NovartisView company profile' ScemblixSearch drug (asciminibSearch drug) has been granted approval by the European Commission (EC) for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemiaSearch disease in chronic phase (Ph+ CMLSearch disease-CP) who have been previously treated with two or more tyrosine kinase inhibitorsSearch drug (TKIsSearch drug). This approval marks a significant advancement in CML therapy, offering a novel mechanism of action for patients who have developed resistance or intolerance to existing TKI treatments.
The EC's decision was based on the pivotal Phase III ASCEMBL trial results, which demonstrated a significant improvement in major molecular response (MMR) rates with ScemblixSearch drug compared to bosutinibSearch drug. Specifically, Scemblix nearly doubled the MMR rate at 24 weeks (25.5% vs. 13.2%, P=.029), and this was confirmed at 96 weeks (37.6% vs 15.8%). Furthermore, the trial showed a more than three-fold lower discontinuation rate due to adverse reactions with Scemblix (5.8%) compared to bosutinib (21.1%) at 24 weeks, which was also confirmed at 96 weeks (7.7% vs 26.3%).
Novel Mechanism of Action
ScemblixSearch drug is the first CMLSearch disease treatment approved in Europe that functions as a STAMP (Specifically Targeting the ABL Myristoyl PocketSearch term) inhibitor. This unique mechanism allows the drug to specifically target the ABL myristoyl pocket, offering a different therapeutic approach for patients who have not responded well to traditional TKI therapies. The STAMP inhibition helps in overcoming mutations at the defective BCR::ABL1 gene, which is associated with the over-production of leukemic cells.
Clinical Significance
Dr. Andreas Hochhaus, Head of the Department of Hematology and Medical Oncology at Jena University Hospital in Germany, noted the importance of this approval, stating, "Until now, patients with CMLSearch disease in Europe had oral TKI therapies with the same mechanism of action to turn to, and those experiencing significant side effects or resistance to these treatment options would often cycle between these very similar therapies, with little success in controlling their disease or improving their quality of life. The approval of ScemblixSearch drug in Europe is a timely milestone that will help many patients find hope for the management of their CML."
Ongoing Research and Global Approvals
NovartisView company profile is actively pursuing regulatory filings for ScemblixSearch drug in multiple countries and regions globally. In October 2021, the US FDA granted accelerated approval for adult patients with Ph+ CMLSearch disease-CP previously treated with two or more TKIsSearch drug and full approval for those with the T315I mutation. Scemblix has also received approval in countries including Japan, Switzerland, and the United Kingdom.
Future Studies
ScemblixSearch drug is currently being evaluated in various treatment lines for CMLSearch disease-CP, both as a monotherapy and in combination therapies. The ASC4FIRST Phase III study (NCT04971226View clinical trial) is evaluating Scemblix in newly diagnosed adult patients with Ph+ CML-CP compared to an investigator-selected TKI, potentially expanding its use to first-line treatment.