Pharma Focus Europe

Boehringer Ingelheim Reaches a Significant Milestone in Chronic Kidney Disease: Promising Phase II Trial Results with an Aldosterone Synthase Inhibitor in Conjunction with Empagliflozin

Saturday, November 04, 2023

Boehringer Ingelheim has released encouraging Phase II data for their experimental compound, BI 690517, an innovative selective aldosterone synthase inhibitor (ASi). The results indicate a substantial reduction in albuminuria, which is a marker of kidney damage, by as much as 39.5% when BI 690517 is combined with empagliflozin, an inhibitor of sodium glucose cotransporters (SGLT2), as compared to a placebo. This study marks the first clinical trial examining this new class of treatment in conjunction with the standard of care, including empagliflozin, for individuals with chronic kidney disease (CKD), a condition impacting more than 850 million people worldwide. The findings were presented as a significant clinical trial at the American Society of Nephrology (ASN) Kidney Week 2023.

BI 690517 operates by inhibiting aldosterone synthase, an enzyme that regulates the final steps in aldosterone synthesis. Elevated aldosterone levels can lead to organ damage and contribute to cardio-renal-metabolic conditions such as hypertension, chronic kidney disease, and heart failure.

Dr. Katherine Tuttle, the Principal Study Investigator and a Professor of Medicine at the University of Washington, stated that this unique trial, combining a selective aldosterone synthase inhibitor with SGLT2 inhibition, demonstrated positive and clinically significant efficacy. This combination may provide additional kidney benefits while potentially reducing the risk of hyperkalemia. Additional treatments for CKD are urgently needed to mitigate the risks of disease progression and severe complications.

Although aldosterone synthase inhibition can result in a moderate increase in serum potassium, this study suggests that empagliflozin's mechanism of action might help mitigate the risk of hyperkalemia when used as a background therapy. This is noteworthy since severe hyperkalemia can lead to changes in medical therapy or hospitalization. As a novel drug class, BI 690517, when used alongside empagliflozin, may address this critical unmet medical need.

A key secondary endpoint in the Phase II trial was a significant reduction in urinary albumin-to-creatinine ratio (UACR), achieved by up to 70% of patients treated with BI 690517 in combination with empagliflozin. These changes in albuminuria may translate into a risk reduction of at least 30% for clinical kidney disease events.

Boehringer Ingelheim, emphasized their commitment to developing innovative treatments for cardio-renal-metabolic conditions affecting over 1 billion people globally. They are eager to proceed with a Phase III trial to further explore the potential of BI 690517 combined with standard care, including empagliflozin.

In 2024, Oxford Population Health and Boehringer Ingelheim will commence recruitment for the international Phase III EASi-KIDNEY trial, involving around 11,000 participants with established CKD at risk of disease progression. The trial aims to definitively assess the efficacy and safety of BI 690517 when used in combination with standard care, including empagliflozin, using Oxford Population Health's streamlined model.

The safety profile of BI 690517 in the Phase II trial was generally acceptable, with modest dose-dependent increases in serum potassium levels, which were partially mitigated when used with empagliflozin. Hyperkalemia occurred at a typical rate for a CKD population, and most episodes did not necessitate medical treatment or discontinuation of BI 690517.



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