AstraZeneca MPO inhibitor shows promise for heart failure patients
pharmafile | July 2, 2021 | News story | Medical Communications |
Results released from AstraZeneca’s Phase IIa SATELLITE trial demonstrated that AZD4831, a myeloperoxidase (MPO) inhibitor, achieved pre-specified target engagement in patients with heart failure with preserved ejection fraction (HFpEF), supporting the further development of this novel therapy.
Findings from a planned interim analysis of the SATELLITE trial showed a 69% reduction in MPO activity in the AZD4831 group from baseline to day 30.1 AZD4831 was generally well tolerated, with no new clinically significant safety findings. The trial was stopped early based on data confirming target engagement and satisfactory safety profile.
In HFpEF, microvascular inflammation is proposed as an underlying mechanism of disease. In a release, AstraZeneca said that AZD4831 represents a novel class of MPO inhibitors, which have been shown to reduce inflammation and fibrosis, and improve microvascular function in preclinical models.
Professor Carolyn Lam, Senior Consultant at the National Heart Centre Singapore and SATELLITE study lead investigator, said: “Heart failure with preserved ejection fraction is associated with high hospitalisation rates, poor quality of life and increased mortality, yet it remains an area of significant unmet need, with limited treatment options. The SATELLITE trial findings shared today show the potential of MPO inhibition with AZD4831 to help address this important need.”
Heart failure (HF) is a chronic disease where half of patients will die within five years of diagnosis. HFpEF occurs when the heart is unable to fill with blood sufficiently, due to increased stiffness of the muscle in the left ventricle and its inability to relax. HFpEF represents about half of all HF cases,6 and is highly prevalent in patients with hypertension, diabetes, obesity, metabolic syndrome or chronic kidney disease.
HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer). Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.
There were no statistically significant differences seen between the AZD4831 and placebo groups in change from baseline in coronary flow velocity reserve and 6-minute walk distance, both secondary endpoints, or in change from baseline in N-terminal pro B-type natriuretic peptide and Kansas City Cardiomyopathy Questionnaire Overall Summary Score, two exploratory endpoints. There were however, numerical increases in exercise capacity and wellness scores in patients treated with AZD4831.
Regina Fritsche Danielson, Senior Vice President and Head of Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said: “These new data from the SATELLITE trial support the further development of AZD4831 as a first-in-class molecule in the treatment of heart failure with preserved ejection fraction. We are also investigating the potential of this exciting therapy in other life-threatening conditions which are driven by inflammatory responses, such as non-alcoholic fatty liver disease, chronic kidney disease and coronary artery disease.”
Kat Jenkins
