vicadrostat (BI 690517) / Boehringer Ingelheim - LARVOL DELTA

Transporter-transporter interplay determines the renal-predominant elimination of the O-glucuronide metabolite (BI 689875) of vicadrostat in humans. (PubMed, Drug Metab Dispos) - "Vicadrostat, an aldosterone synthase inhibitor in development in combination with empagliflozin for chronic kidney disease, heart failure, and cardiovascular risk reduction, undergoes extensive hepatic glucuronidation primarily by UDP-glucuronosyltransferase (UGT)2B7 to form BI 689875, an ether glucuronide metabolite. SIGNIFICANCE STATEMENT: BI 689875, a glucuronide metabolite, is formed in the liver but eliminated in urine. Through proteomics-informed in vitro-in vivo extrapolation, hepatic MRP3 and renal OAT3 were identified as key contributors to its predominant urinary elimination, highlighting interorgan transporter interplay."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease • ABCC3

Aldosterone synthase inhibitors across the translational spectrum: Mechanistic foundations and emerging clinical applications. (PubMed, J Intern Med) - "Next-generation ASIs-including baxdrostat, lorundrostat, dexfadrostat phosphate, and vicadrostat-demonstrate >100-fold selectivity for CYP11B2 over CYP11B1, enabling potent and reversible aldosterone suppression while maintaining cortisol biosynthesis. Collectively, these findings position ASIs as a selective and mechanistically coherent therapeutic strategy that addresses residual aldosterone activity beyond conventional RAAS blockade. Although current evidence relies largely on surrogate endpoints, ongoing phase III outcome trials will determine whether ASIs can translate mechanistic promise into durable cardiovascular and renal protection, potentially redefining the therapeutic landscape of aldosterone-mediated diseases."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Fibrosis • Hypertension • Immunology • Nephrology • Renal Disease • CYP11B1

Comparative Study on the Mode of Action of Vicadrostat and Spironolactone on Protein Profiles and Renal Hemodynamic Effects (COMPARE-VS) (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: University Medical Center Groningen

New P2 trial • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Pharmacodynamics of vicadrostat for aldosterone synthase inhibition in patients with CKD. (PubMed, Eur J Endocrinol) - P2 | "Vicadrostat, with or without background empagliflozin, selectively suppressed aldosterone over cortisol. These findings will be explored in a phase 3 trial program."

Clinical • Journal • PK/PD data • Chronic Kidney Disease • Nephrology • Renal Disease • CYP11B1

Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed. (PubMed, J Clin Med) - "(5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent...Many novel agents-many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)-are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease

Urine Extracellular Vesicle miRNA Changes Induced by Vicadrostat with/Without Empagliflozin in Patients with Chronic Kidney Disease. (PubMed, Int J Mol Sci) - "Vicadrostat plus empagliflozin altered uEV miRNAs involved in immunomodulatory and fibrotic pathways irrespective of participant diabetes status. Regulation of miRNAs may provide insights into synergistic mechanisms of vicadrostat and empagliflozin in CKD treatment."

Journal • Chronic Kidney Disease • Diabetes • Fibrosis • Metabolic Disorders • Nephrology • Renal Disease • MIR192 • MIR194 • MIR199B • MIR27A • MIR381 • MIR513A1

Urine Exosomal miRNA Alterations Induced by Vicadrostat and Empagliflozin in Patients with CKD (KIDNEY WEEK 2025) - P2 | "Conclusion VicaEmpa or VICA alone altered various uEV miRNAs involved in immunomodulatory and fibrotic pathways irrespective of diabetes status. Regulation of miRNAs in the kidney provides insights into mechanisms of action for VICA in CKD."

Clinical • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Metabolic Disorders • Nephrology • Renal Disease

Selectivity of Vicadrostat for Aldosterone Synthase Inhibition: Findings from a Phase 2 Trial in CKD (KIDNEY WEEK 2025) - P2, P3 | "Conclusion Vicadrostat, with or without empagliflozin, selectively suppressed aldosterone levels, without any meaningful effects on cortisol. These findings will be explored further in EASi-HF Preserved™ (NCT06424288), EASi-HF Reduced™ (NCT06935370) and EASi-Kidney™ (NCT06531824) phase 3 trials."

P2 data • Chronic Kidney Disease

Evaluating Aldosterone Synthase Inhibitors in Hypertension: A Meta-Analysis of Efficacy, Safety, and Subgroup Outcomes Across Novel Agents (AHA 2025) - "Four different ASIs - lorundrostat, osilodrostat, baxdrostat, and vicadrostat- were evaluated across the included trials. ASIs appear to be effective and well-tolerated antihypertensive agents, offering significant BP reduction across diverse patient groups, with lorundrostat demonstrating the strongest efficacy. These findings support further large-scale head-to-head trials to better define their role in hypertension management."

Retrospective data • Cardiovascular • Chronic Kidney Disease • Hypertension

EASi-PROTKT Clinical Trail (ChiCTR) - P3 | N=11674 | Not yet recruiting | Sponsor: Peking University Third Hospital; Peking University Third Hospital

Head-to-Head • New P3 trial • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

A Study in Healthy People to Test How 2 Different Formulations of a Combination Treatment (Vicadrostat and Empagliflozin) Are Taken up in the Body and How Food Influences the Amount of the Medicines in the Blood (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study in Healthy People to Test How 2 Different Formulations of a Combination Treatment (Vicadrostat and Empagliflozin) Are Taken up in the Body and How Food Influences the Amount of the Medicines in the Blood (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study in Healthy People to Test How 2 Different Formulations of a Combination Treatment (Vicadrostat and Empagliflozin) Are Taken up in the Body and How Food Influences the Amount of the Medicines in the Blood (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

The Emerging Role of Aldosterone Synthase Inhibitors in Overcoming Renin-Angiotensin-Aldosterone System Therapy Limitations: A Narrative Review. (PubMed, Card Fail Rev) - "Early clinical trials of ASIs (baxdrostat, lorundrostat, vicadrostat, dexfadrostat phosphate, JX09) report significant reductions in aldosterone, blood pressure and albuminuria, with promising safety. Challenges include ensuring high selectivity, mitigating hyperkalaemia and establishing long-term benefits. Ongoing Phase III trials will clarify their efficacy, safety and synergy with additional therapies - including sodium-glucose cotransporter 2 inhibitors - and clinical outcomes, positioning ASIs as an important advance in renin-angiotensin-aldosterone system modulation."

Journal • Review • Cardiovascular • Hypertension • Renal Disease

A Study to Test Whether Vicadrostat in Combination With Empagliflozin Helps People With Chronic Kidney Disease (clinicaltrials.gov) - P2 | N=416 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Nephrology • Renal Disease

A Study to Test Vicadrostat (BI 690517) Taken Together With Empagliflozin in People With Type 2 Diabetes, High Blood Pressure, and Cardiovascular Disease (clinicaltrials.gov) - P3 | N=11800 | Not yet recruiting | Sponsor: Boehringer Ingelheim

Head-to-Head • New P3 trial • Cardiovascular • Congestive Heart Failure • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

A Study in Healthy People to Test How 2 Different Formulations of a Combination Treatment (Vicadrostat and Empagliflozin) Are Taken up in the Body and How Food Influences the Amount of the Medicines in the Blood (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

A Study in Healthy Men to Compare the Amount of Vicadrostat and Empagliflozin in the Blood When Taken Separately and Together (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

A Study in Healthy Men to Compare the Amount of Vicadrostat and Empagliflozin in the Blood When Taken Separately and Together (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study to Test Vicadrostat (BI 690517) Taken Together With Empagliflozin in People With Type 2 Diabetes, High Blood Pressure, and Cardiovascular Disease (clinicaltrials.gov) - P3 | N=11800 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Head-to-Head • Cardiovascular • Congestive Heart Failure • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

A Study in Healthy Men to Compare the Amount of Vicadrostat and Empagliflozin in the Blood When Taken Separately and Together (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed

Pharmacodynamic effects of highly selective aldosterone synthase inhibitor vicadrostat in cynomolgus monkeys: Contrasting effects of once versus twice daily dosing. (PubMed, J Pharmacol Exp Ther) - "Here, the study describes key preclinical studies with the novel aldosterone synthase inhibitor vicadrostat that were instrumental in the design of early clinical studies and provide insight into predicted and unpredicted pharmacodynamic effects. These observations will inform further development of vicadrostat and related drugs for the treatment of kidney disease and other metabolic disease-related morbidities."

Journal • PK/PD data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • CYP11B1

Blood Pressure-Lowering Effects of Aldosterone Synthase Inhibitors-A Systematic Review. (PubMed, Basic Clin Pharmacol Toxicol) - "A significant suppression of cortisol production was found for LCI699 (osilodrostat) but not for baxdrostat, lorundrostat, BI 690517 (vicadrostat) or dexfadrostat. We conclude that ASIs have promising BP-lowering effects with very limited effects on cortisol production and offer reno-protective effects in chronic kidney disease. Studies on hypertensive target organ damage and cardiovascular outcomes are, however, lacking."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Fibrosis • Hypertension • Immunology • Nephrology • Novel Coronavirus Disease • Renal Disease

A Study in Healthy Men to Compare the Amount of Vicadrostat and Empagliflozin in the Blood When Taken Separately and Together (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

A Study to Test Whether Vicadrostat in Combination With Empagliflozin Helps People With Heart Failure (clinicaltrials.gov) - P3 | N=6000 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Nov 2027 ➔ May 2028 | Trial primary completion date: Nov 2027 ➔ May 2028

Head-to-Head • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure