Apecotrep Shows Promise in Reducing Proteinuria in Primary FSGS in Phase 2 trial
In a multicenter, phase 2 trial across 31 centers in 10 countries, apecotrep (BI 764198) reduced proteinuria by 40% over 12 weeks in patients with primary focal segmental glomerulosclerosis (FSGS). The study enrolled 67 participants and met its primary endpoint, with a significant proportion achieving a ≥25% reduction in proteinuria. Apecotrep was well tolerated, supporting its potential as a disease-modifying therapy for primary FSGS.
The results were published in The Lancet and presented at the 2025 American Society of Nephrology (ASN)’s Kidney Week. The Phase III trial is open for recruiting adults and adolescents with primary FSGS. An additional Phase II trial 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. Despite its severity and burden for patients, there are currently no approved targeted therapies. 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.
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. 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. 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. 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. 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.
