Novel aldosterone synthase inhibitor may aid patients with CKD
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Key takeaways:
- BI 690517 dose-dependently reduced urine albumin-to-creatine ratio, showing a potential albuminuria reduction.
- Patients on BI 690517 at 10 mg on background empagliflozin had the largest reduction in this ratio.
PHILADELPHIA — A novel aldosterone synthase inhibitor, BI 690517, was well-tolerated and reduced urine albumin-to-creatinine ratio in patients with chronic kidney disease, according to a presentation at ASN Kidney Week.
“People with CKD remain at high risk of progression despite treatment with [angiotensin-converting enzyme] ACE inhibitors, [angiotensin receptor blockers] ARBs and SGLT2 inhibitors,” Katherine R. Tuttle, MD, FASN, FACP, FNKF, of the University of Washington in Seattle, said. “This clinical trial assessed the efficacy and safety of an aldosterone synthase [AS] inhibitor, BI 690517, with or without empagliflozin in participants with CKD.”
Tuttle and colleagues performed a double-blind, phase 2 trial of 714 adults with CKD on a renin angiotensin system inhibitor (RASi). Patients were selected at random to either receive an 8-week run-in of background empagliflozin 10 mg or a placebo. Participants were then randomly selected again to receive either BI 690517 at 3 mg, 10 mg or 20 mg, or a placebo. Of the 714 patients initially selected, 586 made the second wave of randomization.
The main endpoint was change from the second randomization baseline in urine albumin- to-creatinine ratio (UACR) from the first morning void at week 14. Researchers also measured a UACR of at least 30% reduction from the second randomization at week 14.
During the second randomization, the mean age of patients was 63.8 years; 58.4% of patients were white, 66.6% were men and 70.6% had type 2 diabetes. In addition, median UACR was 426.3 mg/g and mean eGFR was 51.9 mL/min/1.73m2, according to the study abstract.
Results indicated that BI 690517 dose-dependently reduced UACR, pointing to a potential reduction in albuminuria, according to the researchers. The largest drop in UACR was observed in patients who took BI 690517 at 10 mg on background empagliflozin, with a median reduction of 39.5%. For patients on 3 mg to 20 mg of BI 690517, 53.5% of patients on background empagliflozin and 43.2% on placebo empagliflozin background saw UACR changes of at least 30%.
BI 690517 and background empagliflozin together showed additive anti-albuminuric efficacy, the researchers noted, suggesting that the combination may provide greater kidney protection.
In terms of adverse events related to BI 690517 at 3 mg to 20 mg, 19.2% of patients on background empagliflozin and 18.5% of those on placebo empagliflozin background reported issues.
“AS inhibition is a promising new therapy that may add benefit to SGLT2 inhibition for CKD with or without type 2 diabetes,” Tuttle said.
The researchers plan to conduct a phase 3 international trial in 2024 with 11,000 patients.
Reference:
Tuttle KR, et al. FR-OR111. Presented at: ASN Kidney Week; Nov. 2-5, 2023; Philadelphia.
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