Apecotrep Delivers 40% Proteinuria Reduction in Phase 2 FSGS Trial

In a 12-week, 31-center phase 2 clinical trial in 10 countries, apecotrep (BI 764198) reduced proteinuria by 40% in individuals with primary focal segmental glomerulosclerosis (FSGS).1

Boehringer Ingelheim announced the findings, which were published in the Lancet on January 27, 2026, highlighting apecotrep’s potential as a new disease-modifying treatment option for primary FSGS.1

“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 from the board of managing directors at Boehringer Ingelheim, in a company statement. “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.”1

Mechanistically, in FSGS, the transient receptor potential channel 6 (TRPC6) is thought to be overactivated on podocytes, allowing for excessive calcium to enter the cells. This progression causes podocyte injury and loss, ultimately leading to proteinuria and kidney disease progression.1

Apecotrep, a potential first-in-class, oral, selective TRPC6 inhibitor, is being investigated as a novel, targeted, nonimmunosuppressive therapy in FSGS. The therapy is designed to protect podocytes and decrease the rate of disease progression by reducing proteinuria.1,2

“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 lead study investigator Howard Trachtman, MD, from the NYU Langone Medical Center. “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.”1

Tratchman and colleagues conducted a 12-week phase 2 multicenter, double-blind, placebo-controlled, randomized controlled trial to assess 20 mg (n = 18), 40 mg (n = 14), or 80 mg (n = 14) once daily apecotrep compared to placebo (n = 14). They randomized patients in a 1:1:1:1 ratio, stratifying them according to use of corticosteroids. Participants were receiving stable conservative and immunosuppressive therapy, with screening urine protein–creatinine ratio (UPCR) ≥ 1·0 g/g and estimated glomerular filtration rate (eGFR) ≥ 30 mL/min per 1·73 m2.1,2

The primary endpoint was the proportion of participants with proteinuria response, defined as ≥25% UPCR reduction from baseline, at week 12. The other key outcomes were safety and tolerability.1,2

There were 67 participants, 18 to 75 years of age, with biopsy confirmed primary FSGS or with a disease-causing TRPC6 variant. Overall, 37 participants (60%) were male, and 25 participants (40%) were female. The mean age was 40·7 years (Standard Deviation [SD] 12·6) and 63% of the trial cohort were White (39/62).2

Investigators observed proteinuria response in 44% (Odds Ratio [OR], 10·0; 95% Confidence Interval [CI], 1·6–118·1), 14% (OR, 1·5; 95% CI, 0·2–19·5), and 43% (OR, 6·0; 95% CI, 0·9–73·6) in patients receiving 20 mg, 40 mg, or 80 mg apecotrep compared to 1 receiving placebo.2

Overall, investigators noted there were treatment-emergent adverse events reported by 71% of participants (44/62), with similar frequencies of adverse events observed in the placebo group (10/14). Overall, apecotrep was well tolerated with no meaningful differences in adverse event frequencies across treatment arms.2

References

1. Boehringer Ingelheim’s investigational asset apecotrep delivers proteinuria reduction in Phase II kidney trial. Boehringer-ingelheim.com. Published January 27, 2026. Accessed January 28, 2026. https://www.boehringer-ingelheim.com/human-health/chronic-kidney-disease/boehringer-announces-phase-2-results-fsgs-rare-kidney-disease

2. Trachtman H, Kretzler M, Gesualdo L, et al. TRPC6 inhibition for the treatment of focal segmental glomerulosclerosis: a randomised, placebo-controlled, phase 2 trial of BI 764198. The Lancet. Published online January 2026. doi:https://doi.org/10.1016/s0140-6736(25)02255-x