A recent phase 2 trial has indicated that BI 764198, a novel, selective transient receptor potential cation channel, subfamily C, member 6 (TRPC6) inhibitor, significantly reduces proteinuria in patients with focal segmental glomerulosclerosis (FSGS).¹ Overactivity of TRPC6 is believed to contribute to podocyte loss and the progressive decline in kidney function characteristic of FSGS.

BI 764198 is a once-daily oral therapy designed to selectively inhibit TRPC6. By targeting this channel, the treatment aims to prevent podocyte injury and loss, a key pathological feature of FSGS, thereby preserving kidney function.

Study Details

This multicentre, double-blind, placebo-controlled, randomised trial (NCT05213624) assessed the efficacy and safety of BI 764198 over 12 weeks. The study enrolled adults aged 18–75 years with biopsy-confirmed primary FSGS or a disease-causing TRPC6 variant. Participants were on stable conservative and immunosuppressive therapy, with a screening urine protein–creatinine ratio (UPCR) of 1.0 g/g or greater and an estimated glomerular filtration rate of 30 mL/min per 1.73 m² or greater.

A total of 62 participants received treatment and were randomised to receive placebo or BI 764198 at doses of 20 mg, 40 mg, or 80 mg once daily. The primary endpoint was the proportion of participants achieving a proteinuria response, defined as a 25% or greater reduction in UPCR from baseline at week 12.

Key Findings

A proteinuria response was observed in 44% (8/18) of participants receiving 20 mg of BI 764198, 14% (2/14) in the 40 mg group, and 43% (6/14) in the 80 mg group, compared to just 7% (1/14) in the placebo group. The odds ratios versus placebo were 10.0 for the 20 mg dose and 6.0 for the 80 mg dose. Overall, 35% of participants across all BI 764198 dose groups achieved the primary endpoint. The treatment was well tolerated, with similar frequencies of treatment-emergent adverse events reported in the combined BI 764198 groups (71%) and the placebo group (71%).

The study provides promising early data on a novel therapeutic approach for FSGS. The authors concluded, "This is the first evidence of efficacy with a podocyte-targeted therapy in FSGS."¹

Larger randomised controlled trials with longer treatment durations are now planned to further evaluate the safety and efficacy of BI 764198 in FSGS and other conditions associated with podocytopathy.

This study was funded by Boehringer Ingelheim.

Disclaimer

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References

1. 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. Lancet. Published online January 27, 2026. https://doi.org/10.1016/S0140-6736(25)02255-X