Prof BOBBY CHACKO, Dr KATHERINE TUTTLE2, Dr SIBYLLE HAUSKE3,4, Dr LISA CRONIN5, Dr JULIANE MEYERHOFF3, Dr BO JI5, Dr DICK DE ZEEUW6, Dr PETER ROSSING7,8
1John Hunter Hospital, New Lambton Heights, Australia, 2Providence Inland Northwest Health, University of Washington, Spokane, USA, 3Boehringer Ingelheim International, Ingelheim am Rhein, Germany, 4Vth Department of Medicine, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany, 5Boehringer Ingelheim Pharmaceuticals, Ridgefield, USA, 6Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, Groningen, Netherlands, 7Steno Diabetes Center Copenhagen, Herlev, Denmark, 8University of Copenhagen, Copenhagen, Denmark
Biography:
Professor Chacko is Director of Renal Services and Senior Staff Specialist in Nephrology and Transplantation at John Hunter Hospital, and Professor of Medicine at the University of Newcastle, Australia. His expertise is in diabetic kidney disease, IgA nephropathy, hypertension, cardio-renal syndrome, and transplantation. As National Scientific Leader for clinical trials in IgA nephropathy and diabetic kidney disease, he is a prolific researcher and influential voice in nephrology. He chairs the NSW/ACT Renal Advanced Training Recruitment Committee and is a sought-after speaker at national and international forums, recognized for his commitment to excellence in clinical care, education, and research.
Aim:
The NCT05182840 phase II trial investigated the efficacy and safety of vicadrostat (BI690517) alone or in combination with empagliflozin, in participants with chronic kidney disease (CKD) with or without type 2 diabetes (T2D). This subgroup analysis assessed the effects of vicadrostat on albuminuria by KDIGO class at baseline.
Background:
Coadministration of vicadrostat, a highly selective aldosterone synthase inhibitor, with empagliflozin may provide additive efficacy and mitigate risk of hyperkalaemia.
Method:
Adults with CKD (estimated glomerular filtration rate [eGFR] 30–<90 ml/min/1.73m², urine albumin:creatinine ratio (UACR) 200-<5000 mg/g) receiving a maximally tolerated dose of a renin-angiotensin system inhibitor were randomised (R1) 1:1 to receive background empagliflozin 10mg or placebo (PBOEMPA) for 8 weeks. Participants were then re-randomised (R2) 1:1:1:1 to receive vicadrostat (3mg, 10mg, or 20mg) or placebo (PBOVICA) for 14 weeks. Empagliflozin and PBOEMPA data were pooled and the effects of vicadrostat, adjusted for background empagliflozin use, were assessed as change from R2 baseline at Week 14 by KDIGO class.
Results:
Of 583 participants, 40% were moderate/high KDIGO risk and 60% very-high KDIGO risk. Baseline characteristics were similar between the KDIGO risk classes except for higher serum aldosterone, lower eGFR and higher UACR in the very high-risk versus the moderate/high risk group.
Vicadrostat 10mg reduced placebo-adjusted UACR by 24.7% and 47.2% in the moderate/high KDIGO risk group and very-high risk group, respectively (Pinteraction 0.24). UACR reductions of ≥30% were achieved at all vicadrostat doses (10mg: 65% very high-risk group, vs 14% PBOVICA, p<0.001).
Conclusion:
Vicadrostat with and without empagliflozin reduced albuminuria across KDIGO risk class in CKD. Vicadrostat, in combination with empagliflozin will undergo further testing in a Phase 3 trial program (EASi-KIDNEYTM, NCT06531824).