Kidney Week

Abstract: PO0749

Phase Ib Study of the Soluble Guanylate Cyclase Activator BI 685509 in Patients with Diabetic Kidney Disease

Session Information

• Diabetic Kidney Disease: Clinical
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Cherney, David, University of Toronto, Toronto, Ontario, Canada

David Cherney, MD, PhD

• de Zeeuw, Dick, University Medical Center Groningen, Groningen, Netherlands

Dick de Zeeuw,

• L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

• Desch, Marc, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany

Marc Desch,

• Wenz, Arne, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany

Arne Wenz,

• Schulze, Friedrich, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany

Friedrich Schulze,

• Nangaku, Masaomi, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

Masaomi Nangaku,

Background

Soluble guanylate cyclase (sGC) plays a key role in the kidney nitric oxide–cyclic guanosine monophosphate (NO-cGMP) pathway. Increased albuminuria is associated with kidney function loss. The NO-independent sGC activator BI 685509 lowers albuminuria in experimental models. This Phase Ib study (NCT03165227) assessed the safety and efficacy of BI 685509 in patients with diabetic kidney disease and albuminuria.

Methods

This placebo (PBO)-controlled, multiple dose study enrolled patients with type 1 or 2 diabetes, estimated glomerular filtration rate (eGFR) 20–75 mL/min/1.73m² and urinary albumin creatinine ratio (UACR) 200–3500 mg/g. Patients (N=74) were randomised to three active dose groups receiving oral BI 685509 (tested doses after titration: 1 mg three times daily [TID], n=20; 3 mg once daily [QD], n=19; 3 mg TID, n=20) or PBO (n=15) for 28 days. Efficacy was assessed by the proportion of responders, defined as patients with ≥20% decrease from baseline in UACR measured in first morning void (UACR_FMV) and 10-h (UACR_10h) (PBO, 3 mg QD and 3 mg TID only) urine.

Results

At baseline, median eGFR was 47.0 mL/min/1.73m² and median UACR was 641.5 mg/g, although this varied between groups. Drug-related adverse events (AEs) occurred in 12 patients (16.2%; BI 685509 15.3%, PBO 20.0%); the most frequent were hypotension (4.1%) and diarrhoea (2.7%). AEs leading to study discontinuation occurred in 4 patients (5.4%; BI 685509 5.1%, PBO 6.7%). Compared with PBO, the proportion of patients receiving BI 685509 classed as responders was higher (Figure).

Conclusion

BI 685509 treatment was generally well-tolerated with over 50% of patients in the 3 mg QD and 3 mg TID dose groups appearing to show a response in UACR_10h.

Proportion of responders (≥20% decrease from baseline in UACR)

Funding

• Commercial Support –