Novartis Receives FDA Approval for Scemblix (asciminib), a First-in-Class STAMP Inhibitor for Chronic Myeloid Leukemia with Novel Mechanism of Action

On October 30, Novartis announced that the U.S. FDA has approved Scemblix (asciminib) for two distinct indications in chronic myeloid leukemia (CML). The FDA granted accelerated approval to Scemblix for the treatment of Philadelphia chromosome-positive (Ph+) CML patients in the chronic phase who have previously received two or more tyrosine kinase inhibitors (TKIs). Concurrently, the FDA granted full approval for its use in treating the aforementioned patients harboring the T315I mutation. The press release noted that Scemblix is the first CML therapy designed to bind to the myristoyl pocket of ABL1, providing an important new treatment option for patients who are resistant or intolerant to current TKI therapies.

Chronic myeloid leukemia (CML) is a malignant myeloproliferative neoplasm originating from pluripotent hematopoietic stem cells, characterized by a marked increase in granulocytes in the peripheral blood. The Philadelphia (Ph) chromosome and/or the BCR-ABL fusion gene can be detected in a subset of CML patients. For many patients, current therapies are limited by intolerance and resistance. Moreover, patients harboring the T315I mutation develop resistance to most tyrosine kinase inhibitors (TKIs), thereby increasing the risk of disease progression.

Scemblix is an allosteric inhibitor targeting ABL1 that inhibits BCR-ABL1 activity by binding to the myristoyl pocket of ABL1. Since its binding site on BCR-ABL1 differs from that of conventional TKIs, it may address TKI resistance and intolerance in CML patients receiving later-line treatment.

▲ Mechanism of action of Scemblix (Image source: Reference [2])

This approval is based on results from a Phase 3 clinical trial and a Phase 1 clinical trial. The Phase 3 trial results demonstrated that Scemblix nearly doubled the major molecular response (MMR) rate in patients at 24 weeks compared with the active comparator (25.5% vs. 13.2%, p=0.029). Furthermore, the proportion of patients discontinuing treatment due to adverse events was one-third that of the comparator group (7% vs. 25%).

Note: The original text has been abridged.

References:

[1] FDA approves Novartis Scemblix® (asciminib), with novel mechanism of action for the treatment of chronic myeloid leukemia. Retrieved October 29, 2021, from https://www.globenewswire.com/news-release/2021/10/29/2323914/0/en/FDA-approves-Novartis-Scemblix-asciminib-with-novel-mechanism-of-action-for-the-treatment-of-chronic-myeloid-leukemia.html

[2] Hughes, et al. (2019). Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. NEJM, DOI: 10.1056/NEJMoa1902328

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