CUMULATIVE EFFECTS OF THE ALDOSTERONE SYNTHASE INHIBITOR VICADROSTAT COMBINED WITH EMPAGLIFLOZIN ON ALBUMINURIA IN PEOPLE WITH CKD

Introduction:

A phase II trial reported efficacy and safety of the aldosterone synthase inhibitor (ASi) vicadrostat (BI 690517) in chronic kidney disease (CKD), showing albuminuria reduction with or without empagliflozin in the background of up to 40%. This post hoc analysis estimates the cumulative effects of vicadrostat and empagliflozin 10mg on urine albumin:creatinine ratio (UACR) with comparisons to vicadrostat alone, empagliflozin alone, and placebo (PBO).

Methods:

Participants receiving a maximally tolerated dose of a renin-angiotensin system inhibitor were first randomized (R1) to an 8-week run-in period to receive empagliflozin 10 mg daily or empagliflozinPBO, followed by a second randomization (R2) to a 14-week treatment period to receive vicadrostat (3, 10, or 20 mg daily) or vicadrostatPBO. For the run-in period, empagliflozin effects were assessed by pooling participants into empagliflozin vs empagliflozinPBO groups, regardless of vicadrostat dose levels at R2. Randomized vicadrostat dose groups on top of empagliflozin/empagliflozinPBO were assessed from R2 to week 14. R2 served as the baseline reference time point, and mixed-effect model for repeated measures was used to assess change in UACR. Cumulative effects of both vicadrostat and empagliflozin were calculated by adding UACR changes from R1 to R2 and R2 to the end of treatment period.    

Results:

UACR data were available from 249 participants randomized at R1 to receive empagliflozin 10 mg and 254 who received empagliflozinPBO. Estimated cumulative effects on UACR reduction from R1 to week 14 were larger with 10 mg vicadrostat+empagliflozin (-61%) compared to 10-mg vicadrostat alone (-40%) and vs vicadrostatPBO+empagliflozinPBO (-3%) (Figure). 

Conclusions:

Larger UACR reductions across all doses of vicadrostat were achieved in participants with CKD who received both active components (vicadrostat+empagliflozin) compared to treatment with either vicadrostat or empagliflozin alone, suggesting additive effects of the combination on UACR reduction. Combination of an ASi with an SGLT2 inhibitor is a promising, novel therapy strategy that may afford superior benefits over aldosterone synthase or SGLT2 inhibition alone and will be tested further in a phase III clinical trial (EASi-KIDNEY, NCT06531824).

This abstract was also submitted to the ASN 2024 congress as ‘Cumulative effects of aldosterone synthase and SGLT2 inhibition on albuminuria in people with CKD’. 

I have potential conflict of interest to disclose.
PR declares receiving consultancy and/or speakers’ fees to his institution from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Novo Nordisk, Sanofi and Vifor Pharma; and research grants from AstraZeneca and Novo Nordisk

I did not use generative AI and AI-assisted technologies in the writing process.