AstraZeneca Halts Phase I Trial of MCL-1 Inhibitor AZD5991 Due to Cardiac Safety Concerns

Compiled & Translated by丨newborn

According to an update on the ClinicalTrials.gov database, AstraZeneca has suspended a Phase 1 clinical trial of its investigational blood cancer drug, the MCL-1 inhibitor AZD5991. The trial aims to evaluate the efficacy and safety of AZD5991 as a monotherapy or in combination with AbbVie/Roche's approved blood cancer drug Venclexta (venetoclax) for the treatment of relapsed or refractory hematologic malignancies.

In an interview with FierceBiotech, AstraZeneca stated that signs of cardiac issues were observed in a patient receiving AZD5991. Specifically, in a patient with relapsed/refractory acute myeloid leukemia (AML) and other comorbidities, cardiovascular laboratory parameters—specifically blood pressure—exhibited an asymptomatic elevation.

Consequently, AstraZeneca has halted patient dosing in the trial and voluntarily suspended the study. The company has now confirmed that the trial has also been placed on clinical hold by the FDA. It should be noted that this case of asymptomatic hypertension occurred in the combination therapy group receiving AZD5991 and Venclexta. This cardiovascular adverse event was not observed in the patient group receiving AZD5991 monotherapy.

An AstraZeneca spokesperson noted: “Notably, the asymptomatic blood pressure elevation has been resolved. We are now conducting a comprehensive analysis of the study data and working closely with the FDA to benefit patients.”

Two years ago, Amgen’s hematologic cancer drug AMG 397 also faced development setbacks due to cardiac safety concerns. Like AZD5991, it is an MCL-1 inhibitor, and its clinical trial was placed on clinical hold by the U.S. FDA. Earlier this year, Amgen decided to shift its focus to a backup MCL-1 inhibitor, AMG 176.

References:

1.FDA slaps clinical hold on AstraZeneca cancer drug amid heart safety scare in combo test

2.Amid Amgen's similar struggles, AstraZeneca slams the brakes on MCL-1 blood cancer drug