Boehringer Ingelheim’s investigational asset apecotrep delivers proteinuria reduction in Phase II ki

Not intended for the UK

• Apecotrep (BI 764198) is a potential first-in-class, oral, selective TRPC6 inhibitor being investigated as a novel, targeted, non-immunosuppressive therapy in people with primary focal segmental glomerulosclerosis (FSGS).
• Primary FSGS is a rare kidney condition in which injury and loss of podocytes, the cells responsible for the kidney’s filtration system, lead to proteinuria and kidney failure over time.
• Phase II trial results, published in The Lancet, demonstrated a 40% reduction in proteinuria with apecotrep (20 mg dose group) compared to placebo after 12 weeks of treatment.
• The Phase III trial is open for recruiting adults and adolescents with primary FSGS. An additional Phase II trial in other proteinuric kidney diseases will start in the first quarter of this year.

Boehringer Ingelheim today announced results from a 12-week Phase II clinical trial evaluating apecotrep (BI 764198), an oral, potential first-in-class, non-immunosuppressive TRPC6 inhibitor for people with primary focal segmental glomerulosclerosis (FSGS). Apecotrep reduced proteinuria, a key indicator associated with kidney damage, by 40% in the 20 mg dose group compared to placebo.1 

The results were published in The Lancet and presented at the 2025 American Society of Nephrology (ASN)’s Kidney Week. The Phase III trial (NCT07220083) is open for recruiting adults and adolescents with primary FSGS. An additional Phase II trial (NCT07355296) evaluating the safety and efficacy of apecotrep in other proteinuric kidney diseases will start in the first quarter of this year.

Apecotrep demonstrates Boehringer’s commitment to addressing high unmet medical needs across a broad spectrum of kidney diseases. This includes primary kidney conditions where no approved disease-modifying therapies currently exist.

“The results underscore Boehringer’s scientific leadership in kidney health and deep commitment to people living with cardiovascular, renal, and metabolic diseases, including rare kidney conditions like FSGS,” said Paola Casarosa, Head of Innovation Unit, Board of Managing Directors, Boehringer Ingelheim. “With the Phase III trial now underway, we are advancing apecotrep driven by the potential to deliver the first disease-modifying treatment for primary FSGS and redefine the standard of care for patients.”

Primary FSGS is a rare, progressive kidney disease which can end in kidney failure.2,3,4 Despite its severity and burden for patients, there are currently no approved targeted therapies.5,6,7 There remains a significant unmet need for a targeted therapy that addresses the root cause of the disease.

“Primary FSGS is a serious glomerular disease and an important cause of kidney failure in both children and adults. By targeting the underlying mechanism of primary FSGS, apecotrep reduced proteinuria by 40% compared to placebo, with a favorable tolerability profile in adults,” said Howard Trachtman, Lead Investigator, University of Michigan. “These clinically relevant findings reinforce the importance of further investigation of its potential as a first-in-class targeted treatment for primary FSGS, where the unmet need remains high.”

In primary FSGS, the protein Transient Receptor Potential Channel 6 (TRPC6) is hypothesized to be overactivated on podocytes, cells responsible for the kidney’s filtration system.8 This allows excessive calcium to enter the cells, causing progressive podocyte injury and loss, and ultimately, proteinuria and kidney disease progression. Apecotrep intends to protect podocytes and slow down disease progression by decreasing proteinuria.9 

Highlighting its potential as a new treatment option for primary FSGS, apecotrep was granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China and Orphan Drug Designations by the European Medicines Agency (EMA) and the Japanese Ministry for Health, Labour and Welfare (MHLW).

About apecotrep (BI 764198) and the Phase II trial

Apecotrep is an investigational, potential first-in-class, oral, once daily, non-immunosuppressive TRPC6 inhibitor that is being developed as a potential treatment for people living with primary FSGS.9 Its mechanism of action intends to counter the overactivation of TRPC6, a protein channel essential for the structure and function of podocytes, which are specialized cells responsible for the kidney’s filtration system.9 The compound was discovered and developed by Boehringer Ingelheim, and is part of its Cardiovascular-Renal-Metabolic portfolio. 

In the Phase II trial, a response to treatment defined as greater than or equal to 25% reduction in urine protein-creatinine ratio (UPCR) was observed in 35% of participants receiving apecotrep across all dose groups after 12 weeks, compared to 1 out of 14 (7.1%) in the placebo arm. The greatest proportion of patients responding to apecotrep were in the 20mg dose (44.4%). Furthermore, a 40% (p=0.0024) reduction in UPCR compared to placebo was observed with 20 mg dose.1 Finally, apecotrep was generally well-tolerated.

About FSGS

Focal segmental glomerulosclerosis (FSGS) is a type of podocytopathy in which podocyte injury and loss result in excess protein in the urine (proteinuria). Approximately, 50% of people with primary FSGS progress to end-stage kidney disease (ESKD) within 5-10 years.10 FSGS is a leading cause of nephrotic syndrome in adults and is estimated to affect up to 0.8 per 100,000 population globally.7 The condition is associated with scarring in the kidney’s filtering units called glomeruli and causes swelling of legs and other parts of the body, foamy urine, fatigue, weight gain, high blood pressure, and cholesterol increase.11 Primary FSGS means that the disease occurs without a known cause, while secondary FSGS is caused by another known cause such as infection, diabetes or obesity.11 Additionally, genetic FSGS results from mutations in podocyte or glomerular basement membrane proteins or specific susceptibility genes such as TRPC6.12,13 

About Boehringer Ingelheim

Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at www.boehringer-Ingelheim.com.  

References

1 Trachtman H, et al. TRPC6 inhibition for the treatment of focal segmental glomerulosclerosis: a randomized, placebo-controlled, phase 2 trial of BI 764198. Lancet. 2026;S0140-6736(25)02255-X.

2 Rosenberg AZ, Kopp JB. Focal segmental glomerulosclerosis. Clinical Journal of the American Society of Nephrology. 2017;12:502–517. 

3 Munis MA, et al. Incidence and proportion of primary focal segmental glomerulosclerosis (FSGS) among a racially and ethnically diverse adult patient population between 2010 and 2021. Clinical Journal of the American Society of Nephrology. 2025;20(2):229-238.

4 Ossareh S, et al. Kidney outcome in primary focal segmental glomerulosclerosis (FSGS) by using a predictive model. Iranian Journal of Kidney Diseases. 2021;15(6):408-418.

5 Buttgereit F, et al. Optimised glucocorticoid therapy: the sharpening of an old spear. Lancet 2005;365:801–803.

6 Trachtman H. Emerging drugs for treatment of focal segmental glomerulosclerosis. Expert Opinion on Emerging Drugs. 2020;25(3):367-375.

7 McGrogan A, et al. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrology Dialysis Transplantation. 2011;26(2):414-30.

8 Kim EY, et al. Changes in podocyte TRPC channels evoked by plasma and sera from patients with recurrent FSGS and by putative glomerular permeability factors. Molecular Basis of Disease. 2017;1863(9):2342-2354.

9 Trachtman H, et al. TRPC6 inhibitor BI 764198 in focal segmental glomerulosclerosis: Phase 2 study design. Kidney International Reports. 2023;;8(12):2822-2825. 

10 Bensink ME, et al. Kidney failure attributed to focal segmental glomerulosclerosis: a USRDS retrospective cohort study of epidemiology, treatment modalities, and economic burden. Kidney Medicine. 2023;6(2):100760. 

11 Mayo Clinic. Focal segmental glomerulosclerosis (FSGS). Available at: https://www.mayoclinic.org/diseases-conditions/fsgs/symptoms-causes/syc-20354693. Accessed January 2026.

12 Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International. 2021;100:S1-S276.

13 Winn MP et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science. 2005;308(5729):1801-4.