Kidney Week

Abstract: SA-OR046

TRPC6 Inhibition for the Treatment of FSGS: Phase 2 Randomized Controlled Trial of BI 764198

Session Information

• Glomerular Targeted Therapies: The New Era
  November 08, 2025 | Location: Room 310A, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Cross, Nicholas, Department of Medicine, University of Otago, Christchurch, New Zealand

Nicholas Cross, MBChB, PhD

• Trachtman, Howard, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, United States

Howard Trachtman, MD, FASN

• Kretzler, Matthias, Medicine/Nephrology and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Gesualdo, Loreto, Dipartimento Dell'Emergenza E Dei Trapianti Di Organi, Università Degli Studi Di Bari Aldo Moro, Bari, Apulia, Italy

Loreto Gesualdo, DrMed

• Workeneh, Biruh, Department of Nephrology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States

Biruh Workeneh, MD, FASN

• Kaufeld, Jessica Katharina, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany

Jessica Katharina Kaufeld, MD

• Meijers, Björn Ki, Department of Microbiology, Immunology, Transplantation, KU Leuven, and Department of Nephrology, UZ Leuven, Leuven, Belgium

Björn Ki Meijers, MD, PhD

• Ye, Zhiming, Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

Zhiming Ye

• Chen, Qinkai, Department of Nephrology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China

Qinkai Chen, MD

• Derebail, Vimal K., UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, Chapel Hill, North Carolina, United States

Vimal K. Derebail, MD, MPH, FASN

• Ng, Monica Suet Ying, Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Faculty of Medicine, University of Queensland, Herston, Queensland, and Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Herston, Queensland, Australia

Monica Suet Ying Ng, MBBS, PhD

• Ji, Bo, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States

Bo Ji, PhD

• Lobmeyer, Maximilian T, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Maximilian T Lobmeyer, PhD

• Retlich, Silke, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany

Silke Retlich, PhD

• Licariao Rocha, Fabia Tais, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Fabia Tais Licariao Rocha, MD

• Prasad, Srinivasa, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States

Srinivasa Prasad, PhD

• Soleymanlou, Nima, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States

Nima Soleymanlou, PhD

Background

Focal segmental glomerulosclerosis (FSGS) is a relevant histopathological finding in individuals presenting with proteinuria, resulting in kidney failure in 50% within 5–10 years. In FSGS, transient receptor potential cation channel, subfamily-C, member-6 (TRPC6) overactivity may cause podocyte loss and progressive kidney function decline. TRPC6 inhibition may be a novel podocyte-targeted therapy as TRPC6 gain-of-function mutations cause autosomal dominantly inherited FSGS (genetic FSGS).

Methods

Multicenter, Phase 2, double-blind, placebo-controlled, randomized (1:1:1:1) trial assessing efficacy and safety of an oral selective TRPC6 inhibitor (BI 764198) administered once daily (20 mg/40 mg/80 mg versus placebo) over 12 weeks in patients with primary FSGS or genetic FSGS due to known TRPC6 mutations. Patients were receiving stable conservative and immunosuppressive therapy with screening urinary protein:creatinine ratio (UPCR) of ≥1.0 g/g and estimated glomerular filtration rate of ≥30 mL/min/1.73 m². The primary endpoint was the proportion of patients with a proteinuria response (≥25% UPCR reduction from baseline) at Week 12. Other key outcomes were safety, tolerability, and pharmacokinetics.

Results

Sixty patients (7 with TRPC6 mutations) were treated and evaluable. Proteinuria responses at Week 12 were observed in 44.4% (8/18), 14.3% (2/14), and 42.9% (6/14) of patients receiving BI 764198 20 mg, 40 mg, and 80 mg, respectively, versus 7.1% (1/14) receiving placebo. In patients with TRPC6 mutations, 100% (4/4) receiving BI 764198 achieved a proteinuria response at Week 12 versus 0% (0/3) receiving placebo. The highest placebo-corrected mean change in UPCR at Week 12 was observed with the 20 mg dose: −39.82% (95% CI −56.17 to −17.36; p=0.002). BI 764198 was safe and well tolerated with no meaningful differences in adverse event frequencies across treatment arms.

Conclusion

BI 764198 lowered proteinuria in FSGS and was well tolerated. This is the first evidence of efficacy with a podocyte-targeted therapy in FSGS.

Funding

• Commercial Support – The study was supported and funded by Boehringer Ingelheim. Medical writing support in the preparation of this abstract was provided by Laura George, PhD, CMPP of OPEN Health Communications, and funded by Boehringer Ingelheim, in accordance with Good Publication Practice (GPP) guidelines (www.ismpp.org/gpp-2022).

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025dwp4gpkf