Novartis Launches Phase 3 Trial in China for Asciminib (ABL001), Recently Approved by U.S. FDA for Chronic Myeloid Leukemia

By Medicine Observer

On November 15, the Chinese Clinical Trial Registry and Information Disclosure Platform showed that Novartis had launched a Phase 3 clinical trial in China for ABL001 (asciminib) to treat newly diagnosed Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) in adult patients in the chronic phase. Public information indicates that ABL001 (asciminib) is an ABL1 allosteric inhibitor. Not long ago, the drug was just approved by the U.S. FDA for marketing to treat two different indications of chronic myeloid leukemia.

Screenshot source: Drug Clinical Trial Registration and Information Disclosure Platform

CML is a malignant myeloproliferative neoplasm that occurs in pluripotent hematopoietic stem cells, characterized by a significant increase in granulocytes in the peripheral blood. In some CML patients, the Philadelphia chromosome and/or BCR-ABL fusion gene can be detected. Although there are currently multiple tyrosine kinase inhibitors (TKIs) available for the treatment of CML, patients with disease relapse may develop resistance or intolerance to subsequent TKI therapies.

ABL001 is an allosteric inhibitor targeting ABL1. It inhibits the activity of BCR-ABL1 by binding to the myristoyl pocket of ABL1. Since its binding site to BCR-ABL1 differs from that of common TKIs, ABL001 may address the issues of TKI resistance and intolerance in later-stage CML treatment. In February this year, the FDA granted it Breakthrough Therapy designation.

▲ABL001 (asciminib) Mechanism of Action (Image Source: Reference [2])

At the end of October 2021, the FDA granted accelerated approval to ABL001 for marketing, indicated for Philadelphia chromosome-positive CML patients in the chronic phase who had previously received treatment with two or more TKIs. Concurrently, the FDA also granted full approval to ABL001 for treating the aforementioned patients carrying the T315I mutation. The press release noted that ABL001 is the first CML therapy to bind to the myristoyl pocket of ABL1.

Phase 3 clinical trial results showed that, compared with the active control, ABL001 nearly doubled the major molecular response rate (MMR) in patients at 24 weeks (25.5% vs 13.2%). Additionally, the proportion of patients who discontinued treatment due to adverse reactions was one-third in the ABL001 group compared to the control group (7% vs 25%).

In July this year, ABL001 was approved for clinical research in China. According to the Drug Clinical Trial Registration and Information Disclosure Platform, the trial Novartis has initiated is a randomized, open-label, parallel-group international multicenter Phase 3 clinical study. It aims to compare the safety and efficacy of ABL001 with investigator-selected TKIs in newly diagnosed adult patients with chronic-phase Philadelphia chromosome-positive CML. The study will recruit 402 patients globally, including 36 patients planned to be enrolled within China.

We hope that the clinical research of ABL001 in China will proceed smoothly and achieve good results, bringing new treatment options to patients as soon as possible.

References:

[1] Official website of the Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Nov 15, 2021, from http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml

[2] 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

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

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