balcinrenone (AZD9977) / AstraZeneca - LARVOL DELTA

A Phase III Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With CKD Stage 3b and 4 (BalanceD-CKD) (clinicaltrials.gov) - P3 | N=2800 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

Initial Changes in eGFR during Treatment with Balcinrenone and Dapagliflozin: An Exploratory Analysis of the MIRO-CKD Trial. (PubMed, Clin J Am Soc Nephrol) - "In adults with CKD, balcinrenone/dapagliflozin induced a modest acute eGFR reduction which was reversible after treatment discontinuation, did not lead to increased rates of adverse events, and was associated with greater SBP and UACR lowering."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Study of the Effect of Haemodialysis on the Pharmacokinetics, Safety, and Tolerability of Balcinrenone/Dapagliflozin (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Renal Disease

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor. (PubMed, J Clin Pharmacol) - "Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study."

Clinical • Journal • PK/PD data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Study to evaluate the effect of balcinrenone/dapagliflozin in patients with heart failure and impaired kidney function (BalanceD-HF): background and design (ESC 2026) - "BalanceD-HF is a unique trial evaluating the efficacy and safety of the novel nsMRA balcinrenone combined with dapagliflozin in patients with HF and impaired kidney function across the LVEF spectrum and HF care continuum."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Study of the Effect of Haemodialysis on the Pharmacokinetics, Safety, and Tolerability of Balcinrenone/Dapagliflozin (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Renal Disease

The effect of mild and moderate hepatic impairment on the pharmacokinetics, safety and tolerability of balcinrenone. (PubMed, Br J Clin Pharmacol) - "Compared with participants with normal hepatic function, balcinrenone exposure was similar in participants with mild hepatic impairment. AUC, but not Cmax, was slightly increased in participants with moderate hepatic impairment. We do not consider the minor AUC increase seen in participants with moderate hepatic impairment to be clinically relevant. Thus, we would not recommend any dose adjustment for patients with mild or moderate hepatic impairment."

Journal • PK/PD data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hepatology • Liver Failure

Renoprotective Effects of Balcinrenone on Renal Injury and Fibrosis in Acute Kidney Injury and Acute Kidney Disease Models (ERA 2026) - "Conclusion Balcinrenone provides significant renoprotection by attenuating early kidney in the AKI stage and suppressing the progression to AKD through its potent anti-fibrotic effects. These findings suggest that balcinrenone may represent a promising therapeutic strategy for preventing post-AKI renal fibrotic progression."

Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Glomerulonephritis • Immunology • Inflammation • Nephrology • Renal Disease • Reperfusion Injury

Acute changes in eGFR during treatment with balcinrenone and dapagliflozin: An exploratory analysis of the MIRO-CKD trial (ERA 2026) - No abstract available

Chronic Kidney Disease

Balcinrenone, a Non-steroidal Mineralocorticoid Receptor Modulator, Attenuates Renal Fibrosis in a Rodent Model of Unilateral Ureteral Obstruction (ERA 2026) - No abstract available

Preclinical • Fibrosis • Immunology

A Phase III Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With CKD Stage 3b and 4 (BalanceD-CKD) (clinicaltrials.gov) - P3 | N=2800 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

EFFECTS ON SERUM POTASSIUM AND RISK OF HYPERKALAEMIA WITH BALCINRENONE AND DAPAGLIFLOZIN; A SUB ANALYSIS OF THE PHASE 2B MIRO-CKD TRIAL IN PATIENTS WITH CKD (ISN-WCN 2026) - P2 | "Participants were randomised 1:1:1 to oral balcinrenone/dapagliflozin 15 mg/10 mg, balcinrenone/dapagliflozin 40 mg/10 mg or placebo/dapagliflozin 10 mg for 12 weeks.Results MIRO-CKD has recently been completed, and the primary results will be released later this year. The results will be submitted for presentation at the WCN Annual meeting 2026.Conclusion The secondary analyses of effects on serum potassium and hyperkalaemia to be presented at the WCN Annual meeting will provide further understanding of the safety and tolerability of the novel combination of balcinrenone and dapagliflozin in a contemporary CKD population at increased risk of disease progression and with an increased risk of hyperkalaemia.I have potential conflict of interest to disclose.HJLH is a consultant for AstraZeneca, Alexion, Amgen, Bayer, Boehringer Ingelheim, Dimerix, Eli-Lilly, Novartis, NovoNordisk, Roche, and Travere Therapeutics. He has received research support from AstraZeneca,..."

Clinical • P2b data • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Type 2 Diabetes Mellitus

Established and emerging pharmacologic options and unmet need in HFpEF and HFmrEF. (PubMed, ESC Heart Fail) - "Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduced HF events and cardiovascular deaths in participants with HF and EF ≥40% in the FINEARTS-HF trial, and is under evaluation for HFpEF and HFmrEF in the REDEFINE-HF and CONFIRMATION-HF trials. Trials of glucagon-like peptide-1 receptor agonist (GLP-1 RA), semaglutide, and dual glucose-dependent insulinotropic polypeptide receptor agonist/GLP-1 RA, tirzepatide, for HFpEF with obesity, observed an impact on HF hospitalization events and quality of life. Trials of selective mineralocorticoid modulator, balcinrenone, and aldosterone synthase inhibitor, vicadrostat, will address key evidence gaps and help improve outcomes for patients with HFpEF and HFmrEF."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Genetic Disorders • Heart Failure • Nephrology • Obesity • Renal Disease

Balcinrenone shows a unique regulation of potassium excretion in streptozotocin-induced diabetes in male mice. (PubMed, Endocrinology) - "Conversely, gene expression of Ca2+ ion channel subunits, voltage-dependent L type, calcium channel subunit alpha 1C (Cav1.2) and ryanodine receptor 2 (Ryr2), in LV was lower in diabetic but not eplerenone- or balcinrenone-treated diabetic mice. Although balcinrenone and eplerenone similarly modified cardiac changes, potassium excretion was greater with balcinrenone, consistent with a reduced risk of hyperkalemia with the non-steroidal MR modulator."

Journal • Preclinical • Cardiovascular • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • MYH7

The novel mineralocorticoid receptor modulator balcinrenone protects against diet-induced cardiac microvascular dysfunction and plasma potassium elevation in mouse models. (PubMed, PLoS One) - "Urinary K+ excretion was not affected by balcinrenone or eplerenone treatment, but fecal K+ excretion was elevated in CKD mice that were administered balcinrenone versus eplerenone. These results suggest that balcinrenone may be suitable for patients requiring additional cardiorenal protection through MR modulation but are at high risk of hyperkalemia."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Fibrosis • Heart Failure • Nephrology • Renal Disease • IL6

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

Efficacy and Safety of Balcinrenone in Combination with Dapagliflozin on Albuminuria in Participants with CKD (KIDNEY WEEK 2025) - P2 | "Funding Commercial Support – AstraZeneca Background SGLT2is reduce albuminuria and the risk of CKD progression, and the MRA finerenone has similar effects in T2D with CKD...Methods In this double-blind, active-controlled clinical trial (NCT06350123), adults with eGFR of 25–100–5000 mg/g, and potassium 3.5–5.0 mmol/L, were randomized 1:1:1 to combined balcinrenone/dapagliflozin 15/10 mg, balcinrenone/dapagliflozin 40/10 mg, or placebo/dapagliflozin 10 mg as adjunct to RAS inhibitors for 12 weeks, followed by an 8-week wash-out period...Conclusion In participants with CKD, combined balcinrenone and dapagliflozin was superior to dapagliflozin in reducing albuminuria. The combination was well-tolerated with minor effects on potassium."

Clinical • Combination therapy • Late-breaking abstract • Chronic Kidney Disease • Renal Disease

Augmenting nephroprotection: balcinrenone plus dapagliflozin in chronic kidney disease. (PubMed, Lancet) - No abstract available

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Balcinrenone in combination with dapagliflozin compared with dapagliflozin alone in patients with chronic kidney disease and albuminuria: a randomised, active-controlled double-blind, phase 2b clinical trial. (PubMed, Lancet) - P2 | "In participants with chronic kidney disease at increased risk of disease progression, a fixed dose combination of balcinrenone and dapagliflozin was superior to dapagliflozin alone in reducing albuminuria. Balcinrenone plus dapagliflozin was well tolerated, effects on potassium were minor, and no unexpected safety concerns were identified."

Journal • P2b data • Chronic Kidney Disease • Diabetes • Hypotension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

BalanceD-HF - A phase 3 Study To Evaluate The Effect Of Balcinrenone/dapagliflozin In Patients With Heart Failure And Impaired Kidney Function (NCT06307652) (HFSA 2025) - P3 | "Suspected HF events and the causes of deaths are adjudicated by a blinded Clinical Endpoint Committee. An independent Data Monitoring Committee is monitoring safety data on a regular basis.BalanceD-HF is a unique trial that is evaluating a novel MR modulator (balcinrenone) combined with an SGLT2i (dapagliflozin) in the understudied population of patients with HF (across the LVEF spectrum) and impaired kidney function."

Clinical • P3 data • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Population Pharmacokinetic Analysis of Balcinrenone in Healthy Participants and Participants with Heart Failure and Chronic Kidney Disease. (PubMed, Clin Pharmacokinet) - P1, P2 | "Participants with HF and CKD were observed to have approximately 50% lower apparent clearance compared with healthy participants and those with renal impairment, after adjusting for differences in eGFR. This may indicate that factors other than renal function may impact the apparent clearance of balcinrenone. The impact of the covariates on balcinrenone exposure (AUCss) in the intended patient population was less than 50% relative to a reference participant."

Journal • PK/PD data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

A Study to Investigate the Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics in Fed and Fasted State and Pharmacokinetics of Balcinrenone When Dosed With a P-gp Inhibitor in Healthy Participants. (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

Efficacy and safety of balcinrenone and dapagliflozin for CKD: design and baseline characteristics of the MIRO-CKD trial. (PubMed, Nephrol Dial Transplant) - "MIRO-CKD is a fully recruited global trial enrolling a contemporary CKD population at increased risk of progression and with an increased risk of hyperkalaemia based on their reduced kidney function. The study will assess the efficacy, safety and tolerability of the combination of balcinrenone and dapagliflozin to identify an optimal dose for a future phase 3 study in patients with CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Design and baseline characteristics of MIRO-CKD: a Phase IIb, Randomised, Double-Blind Clinical Trial to Evaluate Effects of Balcinrenone in Combination with Dapagliflozin vs. Dapagliflozin in Patients with CKD (ERA 2025) - P2 | " MIRO-CKD is a phase IIb, international, randomised, double-blind, parallel-group trial in adults with CKD (estimated glomerular filtration rate [eGFR] ≥25 to 100 to ≤5000 mg/g) and potassium ≥3.5 to ≤5mmol/L (NCT06350123), where participants have been randomised 1:1:1 to three treatment arms: balcinrenone/dapagliflozin 15 mg/10 mg, balcinrenone/dapagliflozin 40 mg/10 mg or placebo/dapagliflozin 10 mg for 12 weeks followed by an 8-week wash-out period to assess off-drug effects. MIRO-CKD is a fully recruited global phase IIb trial enrolling a contemporary CKD population at increased risk of disease progression and with an increased risk of hyperkalaemia based on their reduced kidney function. The study will assess the efficacy, safety and tolerability of the combination of balcinrenone and dapagliflozin with the aim to identify an optimal dose for a future phase III study in patients with CKD."

Clinical • Combination therapy • P2b data • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Type 2 Diabetes Mellitus

A Study to Investigate the Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics in Fed and Fasted State and Pharmacokinetics of Balcinrenone When Dosed With a P-gp Inhibitor in Healthy Participants. (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open