Boehringer Ingelheim announced positive results from a global Phase II study of apecotrep (BI 764198), an investigational, oral TRPC6 inhibitor, in patients with primary focal segmental glomerulosclerosis (FSGS). The trial met the primary endpoint of proteinuria reduction compared with placebo.

Boehringer results provide early evidence of target engagement and disease biology modulation in a rare kidney disorder with substantial unmet need. The data, published in The Lancet and detailed in the company release, may inform ongoing development plans for apecotrep and other targeted approaches for proteinuric kidney diseases.

Trial specifics

In the 12-week, randomized, placebo-controlled Phase II study, adults with primary FSGS received daily oral doses of apecotrep, with the 20 mg dose cohort evaluated against placebo. The trial used urine protein-to-creatinine ratio (UPCR) as the primary measure of proteinuria, a surrogate marker for kidney damage and disease progression.

Results showed a 40% reduction in proteinuria in the 20 mg dose group compared with placebo after 12 weeks of treatment, with statistical significance reported at p = 0.0024 for the highest dose. Across all dose groups, a response defined as ≥25% UPCR reduction was observed in 35% of participants versus 7.1% in the placebo arm. Apecotrep was generally well tolerated in this mid-stage cohort, with no unexpected safety signals reported. An ongoing Phase III trial (NCT07220083) is currently recruiting adults and adolescents with primary FSGS, and an additional Phase II study in other proteinuric kidney diseases is scheduled to begin in Q1.

Research context

Apecotrep is designed to selectively inhibit transient receptor potential cation channel subfamily C member 6 (TRPC6), a calcium-permeable ion channel expressed on podocytes, the specialized cells in the kidney glomerulus responsible for filtration. Overactivation of TRPC6 has been implicated in podocyte injury and progressive loss in FSGS and other proteinuric disorders. By modulating TRPC6 activity, apecotrep aims to reduce pathological calcium influx and protect podocyte integrity, thereby decreasing proteinuria and potentially slowing disease progression.

Primary FSGS is a rare glomerular disease characterized by podocyte injury, excessive protein in the urine, and a progressive course that often leads to end-stage kidney disease (ESKD) within years of diagnosis. There are currently no approved targeted therapies for FSGS, with standard care often reliant on corticosteroids, immunosuppressants, and supportive measures such as renin-angiotensin system inhibition. In the broader chronic kidney disease (CKD) landscape, recently approved therapies such as AstraZeneca’s Farxiga (dapagliflozin) and Boehringer’s own Jardiance (empagliflozin) have shown benefits in slowing progression of CKD but are not specific to primary FSGS pathology. Other investigational agents include Novartis’s Vanrafia (atrasentan), an endothelin receptor antagonist approved for proteinuria reduction in IgA nephropathy, and experimental modalities such as antisense oligonucleotides targeting complement pathways in IgA nephropathy, including sefaxersen (RO7434656) in Phase 2/3 testing. Other emerging therapies for proteinuric kidney disease also include candidates emphasizing novel mechanisms, such as oligonucleotide inhibitors or non-immunosuppressive small molecules.