The investigational non-steroidal MRA balcinrenone in cardiorenal medicine: current evidence and future perspectives.

For almost two decades, renin-angiotensin-system (RAS) blockade was the basic pillar of therapy for cardiorenal protection in patients with chronic kidney disease (CKD) and albuminuria. Novel therapies, such as sodium-glucose co-transporter type 2 inhibitors (SGLT2is) and the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone, have been added to our therapeutic armamentarium in the last few years. Despite this substantial progress, there is still an unmet need for the development of additional therapies to mitigate the substantial residual risk of CKD patients. Balcinrenone is a novel, non-steroidal MRA that is currently under investigation for potential cardiorenal protective effects. In preclinical studies, balcinrenone was similarly effective with eplerenone in improving albuminuria and in reversing renal histopathology. Animal studies have shown a beneficial effect of balcinrenone on urinary sodium/potassium ratio that contrasts with the typical increase seen with traditional steroidal MRAs. The MIRO-CKD was a phase 2b trial showing that among 324 patients with albuminuric CKD, combination therapy with dapagliflozin and balcinrenone was safe and more effective than monotherapy with dapagliflozin in improving albuminuria over 3 months of follow-up. A large phase 3 clinical program is ongoing to investigate the long-term safety and efficacy of balcinrenone in a broad spectrum of patients with symptomatic heart failure and moderate-to-advanced CKD. In this article, we explore the tolerability, safety, and efficacy of the investigational non-steroidal MRA balcinrenone. We critically evaluate the design and key findings of the MIRO-CKD trial and provide directions for future research in this important area.