Fixed-dose balcinrenone–dapagliflozin combo works in high-risk CKD

In the treatment of patients with chronic kidney disease (CKD) at high risk of progression, a fixed dose combination of balcinrenone and dapagliflozin is well tolerated and results in greater reductions in albuminuria as compared with dapagliflozin alone in reducing albuminuria, according to the phase IIb MIRO-CKD study.

MIRO-CKD included 324 adult patients with estimated glomerular filtration rate (eGFR) of 25 to <60 mL/min per 1.73 m², urine albumin-to-creatinine ratio (UACR) of >100 to ≤5,000 mg/g, and serum potassium concentration 3.5 to 5 mmol/L.

The patients were randomly assigned to receive combined balcinrenone 15 mg plus dapagliflozin 10 mg (n=108), balcinrenone 40 mg plus dapagliflozin 10 mg (n=110), or dapagliflozin 10 mg plus placebo (n=106) once daily as adjunct to renin angiotensin system inhibitors for 12 weeks, followed by an 8-week wash-out period. The primary efficacy endpoint was relative change in UACR from baseline to week 12.

The mean age of the patients was 64.6 years, 66 percent were male, and 32 percent were Asian. At baseline, the mean age was 64.6 years, the mean eGFR was 42.2 mL/min per 1.73 m², median UACR was 365 mg/g, and 56 percent of the patients were taking SGLT2 inhibitors.

At week 12, UACR decreased by 22.8 percent (90 percent confidence interval [CI], –33.3 to –10.7; p=0.0038) with balcinrenone 15 mg plus dapagliflozin 10 mg vs dapagliflozin 10 mg plus placebo and by 32.8 percent (90 percent CI, –42 to –22.1; p<0.0001) with balcinrenone 40 mg plus dapagliflozin 10 mg vs dapagliflozin 10 mg plus placebo.

In terms of safety, hyperkalaemia occurred in 6 percent of patients in the balcinrenone 15 mg plus dapagliflozin 10 mg group, 7 percent in the balcinrenone 40 mg plus dapagliflozin 10 mg group, and 5 percent in the dapagliflozin 10 mg plus placebo group. Hypotension and renal events were few and similar across the treatment groups, and none were serious. Two patients died during the study, both more than 28 days after the last dose of study drug.