balcinrenone (AZD9977) / AstraZeneca - LARVOL DELTA

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

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 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

MIRO-CKD: Efficacy, Safety and Tolerability of Balcinrenone/Dapagliflozin Compared to Dapagliflozin in Adults With Chronic Kidney Disease (clinicaltrials.gov) - P2 | N=324 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Nephrology • Renal Disease

The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of balcinrenone. (PubMed, Br J Clin Pharmacol) - P2, P3 | "Balcinrenone exposure was approximately two-fold higher in participants with severe renal impairment compared with the group-matched control participants. Based on linear regression analysis of total apparent balcinrenone clearance vs. baseline eGFR, the AUC exposure is predicted to be <50% higher in patients with an eGFR of 20 mL/min/1.73 m2 compared with those with an eGFR of 60 mL/min/1.73 m2. In light of these findings, no dose adjustment based on eGFR is needed in two ongoing studies that target these patients (MIRO-CKD [NCT06350123] and BalanceD-HF [NCT06307652])."

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

BalanceD-HF: Phase III study to evaluate the effect of balcinrenone/dapagliflozin in patients with heart failure and impaired kidney function (ChiCTR) - P3 | N=4800 | Sponsor: Peking Union Medical College Hospital; Peking Union Medical College Hospital

New P3 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

A Phase I PK Study of Balcinrenone/Dapagliflozin in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: AstraZeneca | Not yet recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Oct 2024 | Trial primary completion date: Apr 2025 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date

MIRO-CKD: Efficacy, Safety and Tolerability of Balcinrenone/Dapagliflozin Compared to Dapagliflozin in Adults With Chronic Kidney Disease (clinicaltrials.gov) - P2 | N=324 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ May 2025 | Trial primary completion date: Jan 2026 ➔ May 2025

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease

Balcinrenone/dapagliflozin in patients with heart failure and impaired kidney function – the Phase 3 BalanceD-HF study design (NCT06307652) (CVCT USA 2024) - P3 | No abstract available

Clinical • P3 data • Cardiovascular • Congestive Heart Failure • Heart Failure

MIRACLE: Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease (clinicaltrials.gov) - P2 | N=153 | Completed | Sponsor: AstraZeneca | Phase classification: P2b ➔ P2

Phase classification • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease • NPPB

Concentration-QT modeling demonstrates that the selective mineralocorticoid receptor modulator, balcinrenone (AZD9977), does not prolong QT interval. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Balcinrenone (AZD9977) is a selective mineralocorticoid receptor modulator in development in combination with dapagliflozin for treatment of heart failure with impaired kidney function and chronic kidney disease. Furthermore, the upper 90% ΔΔQTcF CI was estimated to be below the threshold of regulatory concern of 10 ms at all observed concentrations (up to 16.7 μmol/L). Hence, it can be concluded that balcinrenone does not induce QTcF prolongation at the high clinical exposure scenario."

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

Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Balcinrenone (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion • Hepatology

A Phase IIb, Multicentre, Randomised, Double-Blind, Dose-finding Study to Evaluate the Efficacy, Safety and Tolerability of Balcinrenone in Combination with Dapagliflozin Compared with Dapagliflozin in Patients with Chronic Kidney Disease and Albuminuria (ChiCTR) - P2 | N=300 | Not yet recruiting | Sponsor: Zhongshan Hospital, Fudan University; Zhongshan Hospital, Fudan University

Combination therapy • New P2 trial • Chronic Kidney Disease • Nephrology • Renal Disease