Aldosterone inhibitor BI 690517 reduced albuminuria when combined with SGLT2 inhibitor
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Key takeaways:
- Half of participants experienced a clinically meaningful decrease in albuminuria after taking BI 690517.
- Of patients taking BI 690517 with empagliflozin, 70% had a clinically meaningful decrease in albuminuria.
An experimental drug that inhibits aldosterone production reduced albuminuria in patients with chronic kidney disease, according to phase 2 study results published in The Lancet.
The multinational randomized controlled trial tested the efficacy of BI 690517 to reduce risk hyperkalemia in 586 adults taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).
ACE inhibitors and ARBs tend to increase aldosterone levels long-term, while adverse events of aldosterone inhibitors can allow for hyperkalemia, Katherine Tuttle, MD, of the University of Washington School of Medicine and Providence Inland Northwest Health, said in a university press release.
“We’ve known for several decades that aldosterone is a major driver of inflammation and fibrosis in the kidney and also in the heart,” Tuttle said. “It has just been very hard to target therapeutically.”
Researchers tested BI 690517 in three doses alone and combined with SGLT2 inhibitor empagliflozin alongside patients’ ARB or ACE inhibitors. Patients were randomly assigned daily 10 mg doses of empagliflozin or placebo for 8 weeks. After 8 weeks, patients were then randomly assigned a BI 690517 dosage of 3 mg, 10 mg or 20 mg or placebo daily for 14 weeks. Among patients who received BI 690517 without empagliflozin, their urine albumincreatinine ratio change with placebo was –3% (95% CI, –19 to 17). The uACR change was –22% (95% CI, –36 to –7) with the 3 mg dose, –39% (95% CI, –50 to –26) with the 10 mg dose and –37% (95% CI, –49 to –22) with the 20 mg dose.
Among patients who received BI 690517 and empagliflozin, the change in uACR was –11% (95% CI, –23 to 4) with placebo, –19% (95% CI, –31 to –5) with the 3 mg dose, –46% (95% CI, –54 to –36) with the 10 mg dose and –40% (95% CI, –49 to –30) with the 20 mg dose.
Half of patients who received BI 690517 had a 30% or reduction in albuminuria after 14 weeks. Among patients who received BI 690517 and empagliflozin, 70% had a 30% or reduction in albuminuria.
Although BI 690517 was associated with higher rates of hyperkalemia, researchers wrote that most cases did not require medical intervention.
“We think these are high-impact findings,” Tuttle said in the release. “Seventy-five percent of all people on dialysis have diabetes or hypertensive kidney disease, and the agents — if we can get it right in terms of awareness and access and detection at a stage where it’s treatable — might make dialysis almost obsolete. This is in reach.”
Reference:
Outsize benefit seen in trial of drug for kidney disease. https://newsroom.uw.edu/news-releases/outsize-benefit-seen-in-trial-of-drug-for-kidney-disease#:~:text=Although%20sodium%2Dglucose%20cotransporter%2D2,kidney%20disease%20in%2030%20years.%E2%80%9D Published Dec. 18, 2023. Accessed Dec. 18, 2023.
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Tuttle KR, et al. Lancet. 2023:doi:10.1016/S0140-6736(23)02408-X.
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