Prof BOBBY CHACKO1, Prof PETER ROSSING2,3, Dr SIBYLLE HAUSKE4,5, Dr LISA CRONIN6, Dr JULIANE MEYERHOFF4, Dr BO JI6, Dr DICK DE ZEEUW7, Dr KATHERINE TUTTLE8
1John Hunter Hospital, New Lambton Heights, Australia, 2Steno Diabetes Center Copenhagen, Herlev, Denmark, 3University of Copenhagen, Copenhagen, Denmark, 4Boehringer Ingelheim International, Ingelheim am Rhein, Germany, 5University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany, 6Boehringer Ingelheim Pharmaceuticals, Ridgefield, USA, 7Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, Groningen, Netherlands, 8Providence Inland Northwest Health, University of Washington, Spokane, USA
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 body mass index (BMI) 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–<90ml/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 1:1 (R1) 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 the presence or absence of background empagliflozin use, were assessed as change from R2 baseline at Week 14 by BMI subgroups.
Results:
Of 583 participants, 42.7% had BMI ≥30kg/m2 and 57.3% had BMI <30kg/m2. Vicadrostat reduced UACR in participants with BMI ≥30 and <30kg/m2 (10mg: -37.5% and -39.1% with BMI <30kg/m2 and ≥30kg/m2, respectively, Pinteraction = 0.13). UACR reductions of ≥30% were achieved in >50% participants with 10mg and 20mg vicadrostat (BMI ≥30kg/m2: 10mg vicadrostat 61.5%, placebo 18.4%; BMI <30kg/m2: 10mg vicadrostat 50.7%, placebo 26.2%).
Conclusion:
Vicadrostat with or without empagliflozin reduced albuminuria irrespective of baseline BMI dichotomized at 30 kg/m2 in participants with CKD and with or without T2D. Vicadrostat, in combination with empagliflozin will undergo further testing in a phase 3 trial program (EASi-KIDNEYTM, NCT06531824).