#3315 Vicadrostat with and without empagliflozin reduces albuminuria across KDIGO risk class in chronic kidney disease

Abstract Background and Aims Vicadrostat (BI 690517) is a highly selective aldosterone synthase inhibitor in clinical development for CKD treatment. Coadministration of vicadrostat with a sodium-glucose cotransporter-2 inhibitor may provide additive efficacy and mitigate risk of hyperkalemia. This phase II trial (NCT05182840) investigated the efficacy and safety of vicadrostat, given alone or in combination with empagliflozin, in participants with CKD and with or without type 2 diabetes [1, 2]. The aim of the present analyses was to assess effects of vicadrostat on albuminuria by KDIGO risk class. Method Adults with CKD (eGFR 30–<90 ml/min/1.73 m², UACR 200–<5000 mg/g) receiving a maximally tolerated dose of a renin-angiotensin system inhibitor were randomized (R1) 1:1 to receive background empagliflozin 10 mg or matching placebo (PBOEMPA) during an 8-week run-in. They were then re-randomized (R2) 1:1:1:1 to receive vicadrostat (3 mg, 10 mg, or 20 mg) or matching placebo (PBOVICA) for 14 weeks, in addition to their assigned empagliflozin or PBOEMPA. The primary outcome was the change from R2 baseline in urine albumin:creatinine ratio (UACR) at Week 14. Data for empagliflozin and PBOEMPA were pooled and the effects of vicadrostat, adjusted for background empagliflozin use, were assessed by KDIGO risk class (moderate to high or very high) [3]. Results Of 583 participants in the present analyses, 229 (40%) were classed as having moderate or high KDIGO risk and 345 (60%) had very-high KDIGO risk. Baseline demographics and clinical characteristics were similar between the KDIGO risk class groups except for higher serum aldosterone (mean [SD] 172 [174] versus 152 [127] pmol/L), lower eGFR (mean [SD] 41 [9] versus 69 [13] ml/min/1.73 m2) and higher UACR (median [IQR] 905 [313, 1098] versus 566 [166, 607] mg/g) in the very high-risk group versus the moderate or high risk group. With vicadrostat 10 mg, the placebo-adjusted percent UACR change from baseline was −24.7% (95% CI −43.9, 1.1) in the moderate or high KDIGO risk group and −47.2% (−57.2, −34.9) in the very-high risk group (Pinteraction 0.24; Figure). A greater proportion of patients in both the moderate to high and very high risk groups achieved a UACR reduction of ≥30% at all vicadrostat doses tested (10 mg dose group: with moderate or high risk, 24/50 [48%] vs 13/55 [24%] PBOVICA, p < 0.01; very high risk, 45/69 [65%] vs 11/77 [14%] PBOVICA, p < 0.001). Conclusion Vicadrostat with and without empagliflozin reduced albuminuria across KDIGO risk class in chronic kidney disease. Vicadrostat given in combination with empagliflozin shows promise as a potential treatment option for patients with CKD that will undergo further testing in a Phase 3 trial program (EASi-KIDNEYTM, NCT06531824).