Boehringer Ingelheim's Apecotrep Shows 40% Proteinuria Reduction in Phase II Trial for Rare Kidney Disease FSGS
核心洞察
Boehringer Ingelheim's investigational drug apecotrep (搜索) demonstrated a 40% reduction in proteinuria (搜索) compared to placebo in a 12-week Phase II trial for primary focal segmental glomerulosclerosis (搜索) (FSGS (搜索)).
The oral TRPC6 (搜索) inhibitor represents a potential first-in-class, non-immunosuppressive therapy targeting the underlying mechanism of this rare kidney disease that currently has no approved treatments.
Results published in The Lancet have prompted initiation of a Phase III trial recruiting adults and adolescents with primary FSGS (搜索), alongside plans for additional Phase II studies in other proteinuric kidney diseases.
Boehringer Ingelheim announced positive results from a Phase II clinical trial of apecotrep (搜索) (BI 764198), an investigational oral TRPC6 (搜索) inhibitor that achieved a statistically significant 40% reduction in proteinuria (搜索) compared to placebo in patients with primary focal segmental glomerulosclerosis (搜索) (FSGS (搜索)). The 12-week trial results, published in The Lancet and presented at the 2025 American Society of Nephrology Kidney Week, represent a potential breakthrough for a rare kidney disease with no approved targeted therapies.
Novel Mechanism Targets Root Cause of Disease
Apecotrep (搜索) is designed as a potential first-in-class, oral, selective TRPC6 (搜索) inhibitor that targets the underlying pathophysiology of primary FSGS (搜索). In this rare kidney condition, the protein Transient Receptor Potential Channel 6 (搜索) (TRPC6) becomes overactivated on podocytes, the specialized cells responsible for the kidney's filtration system. This overactivation allows excessive calcium to enter the cells, causing progressive podocyte injury and loss, ultimately leading to proteinuria (搜索) and kidney disease progression.
"By targeting the underlying mechanism of primary FSGS (搜索), apecotrep (搜索) reduced proteinuria (搜索) by 40% compared to placebo, with a favorable tolerability profile in adults," said Howard Trachtman, Lead Investigator at the 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."
Significant Clinical Response Rates
The Phase II trial demonstrated that 35% of participants receiving apecotrep (搜索) across all dose groups achieved a treatment response, defined as greater than or equal to 25% reduction in urine protein-creatinine ratio (UPCR), compared to only 7.1% (1 out of 14) in the placebo arm after 12 weeks. The highest response rate was observed in the 20 mg dose group, where 44.4% of patients responded to treatment. This same dose group achieved the statistically significant 40% reduction in UPCR compared to placebo (p=0.0024).
Addressing Critical Unmet Medical Need
Primary FSGS (搜索) represents a significant unmet medical need, affecting up to 0.8 per 100,000 people globally and serving as a leading cause of nephrotic syndrome (搜索) in adults. The disease is characterized by injury and loss of podocytes, leading to proteinuria (搜索) and progressive kidney failure (搜索). Approximately 50% of people with primary FSGS progress to end-stage kidney disease (搜索) within 5-10 years, yet no approved disease-modifying therapies currently exist.
"Primary FSGS (搜索) is a serious glomerular disease and an important cause of kidney failure (搜索) in both children and adults," Trachtman noted, emphasizing the clinical significance of the trial results.
Regulatory Recognition and Development Pipeline
The therapeutic potential of apecotrep (搜索) has been recognized by multiple regulatory agencies. The drug has received Breakthrough Therapy Designation from the Center for Drug Evaluation of China's National Medical Products Administration, as well as Orphan Drug Designations from both the European Medicines Agency and Japan's Ministry for Health, Labour and Welfare.
"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 (搜索)," said Paola Casarosa, Head of Innovation Unit, Board of Managing Directors at Boehringer Ingelheim. "With the Phase III trial now underway, we are advancing apecotrep (搜索) driven by the potential to deliver the first disease-modifying treatment for primary FSGS and redefine the standard of care for patients."
Advancing to Phase III and Beyond
Based on these encouraging Phase II results, Boehringer Ingelheim has initiated a Phase III trial (NCT07220083) that is currently recruiting adults and adolescents with primary FSGS (搜索). Additionally, the company plans to begin an additional Phase II trial (NCT07355296 (搜索)) in the first quarter of this year to evaluate apecotrep (搜索)'s safety and efficacy in other proteinuric kidney diseases, potentially expanding the drug's therapeutic applications.
The compound, discovered and developed by Boehringer Ingelheim as part of its Cardiovascular-Renal-Metabolic portfolio, was generally well-tolerated in the Phase II trial, supporting its continued development as a once-daily, non-immunosuppressive treatment option for patients with this devastating kidney disease.