On October 9, the U.S. Food and Drug Administration (FDA) placed a clinical hold on a trial assessing AstraZeneca’s AZD5991 in combination with venetoclax and as monotherapy for patients with relapsed or refractory acute myeloid leukemia (AML).
AZD5991 is a direct inhibitor of MCL-1 designed to target apoptosis. The trial was placed on hold following a report of “asymptomatic elevation in cardiovascular laboratory parameters,” in a patient with AML and additional comorbidities who was treated with the combination of AZD5991 and venetoclax, according to a statement by AstraZeneca. No safety issues were reported in patients who received AZD5991 monotherapy.
This class of drugs produced similar safety concerns two years ago, when Amgen was asked to place its study of AMG 397, another oral MCL-1 inhibitor, on hold. The company opted to terminate this study to focus on trials of its intravenous MCL-1 inhibitor AMG 176.