A Phase III clinical trial has yielded significant benefits for patients with chronic kidney disease, with an experimental drug showing the ability to reduce albuminuria, a marker of kidney damage, for a majority of participants. The results, published in The Lancet, highlight the potential of the drug candidate, BI 690517, to slow the progression of kidney disease.
Led by Dr. Katherine Tuttle, a clinical professor of nephrology at the University of Washington School of Medicine, the study involved patients who were already receiving standard-care medications for kidney disease. The experimental drug was combined with one of these medications, and the combination produced even more promising results. Seventy percent of participants experienced a significant reduction in albuminuria when the experimental drug was paired with the standard-care medication.
BI 690517 is designed to inhibit the production of aldosterone, a hormone that plays a role in regulating blood pressure. However, excess aldosterone can speed up the progression of kidney disease. The challenge lies in balancing the reduction of aldosterone levels without causing unfavorable side effects, such as hyperkalemia (high blood potassium levels).
The trial addressed this challenge by ensuring that participants had been on standard-care medications, specifically angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), for at least four weeks prior to the study. Additionally, an SGLT2 inhibitor called empagliflozin, known for its kidney-protective properties, was included as background therapy for participants.
SGLT2 inhibitors were primarily developed to lower blood sugar but have emerged as powerful drugs for kidney protection. Dr. Tuttle referred to them as the most significant breakthroughs in kidney disease treatment in the past three decades. One of their secondary benefits is mitigating the risk of hyperkalemia.
The trial, which began in February 2022 and concluded in July 2023, involved 714 patients with a formal diagnosis of kidney disease. They were initially randomized to receive either empagliflozin or a placebo for eight weeks, following which 586 participants were randomly assigned to receive BI 690517 or a placebo for 14 weeks.
The primary measure of efficacy was the reduction in albuminuria levels. The experimental drug alone achieved a clinically meaningful reduction (30% or more) in albuminuria levels for 50% of participants, with the most significant response observed at a dose of 10 mg. When combined with empagliflozin, the reduction in albuminuria levels reached significant levels for 70% of participants.
It is worth noting that the experimental drug was associated with higher rates of hyperkalemia compared to the placebo. However, most cases did not require medical intervention. The researchers also observed that empagliflozin appeared to mitigate the occurrence of hyperkalemia, and its effects on potassium reduction align with previous meta-analyses.
These promising findings will inform a Phase III trial led by Oxford Population Health in England, which will involve 11,000 patient-participants from around the world. Dr. Tuttle believes that these findings have high impact potential, especially considering that 75% of individuals on dialysis have diabetes or hypertensive kidney disease. If awareness, access, and detection improve, the combination therapy could potentially render dialysis obsolete in the future.
Aldosterone has long been recognized as a major driver of inflammation and fibrosis in the kidney and heart, but effectively targeting it therapeutically has been challenging. Dr. Tuttle expressed optimism about the potential of BI 690517 to address this challenge and improve the treatment outcomes for patients with kidney disease.
1. Source: Coherent Market Insights, Public sources, Desk research
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