AZ says MPO inhibitor AZD4831 shows promise in heart failure study

AstraZeneca (AZ) has revealed results from a mid-stage study of its investigational myeloperoxidase (MPO) inhibitor in patients with heart failure with preserved ejection fraction (HFpEF).

The Phase IIa SATELLITE trial is assessing the target engagement, safety and tolerability of AZD4831 in patients with HFpEF – patients involved in the study were randomised 2:1 to receive either a once daily 5 mg dose of the MPO inhibitor, escalated from 2.5 mg on day ten, or placebo for 90 days.

According to a planned interim analysis of the trial, the AZD4831 group showed a 69% reduction in MPO activity from baseline to 30 days.

However, investigators found no statistically significant difference between the AZD4831 and placebo groups on two secondary endpoints.

This included change from baseline in coronary flow velocity reserve (CFVR) and six-minute walk distance (6MWD).

AZD4831 also failed to provide statistically significant benefit on two exploratory endpoints – change from baseline in N-terminal pro B-type natriuretic peptide and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS).

AZ noted that there were numerical increases in exercise capacity (6MWD) and wellness (KCCQ-OSS) scores in AZD4831-treated patients.

An ad hoc exploratory analysis of molecular signatures using data from the Phase IIa trial also showed that proteomic abnormalities associated with increased morbidity and mortality in HFpEF patients were partially reversed by AZD4831 treatment.

“[This] new data from the SATELLITE trial [supports] the further development of AZD4831 as a first-in-class molecule in the treatment of heart failure with preserved ejection fraction,” said Regina Fritsche Danielson, senior vice president and head of research and early development, cardiovascular, renal and metabolism (CVRM), BioPharmaceuticals R&D at AZ.

“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,” she added.