APPLAUSE-IgAN: Slower kidney function decline with iptacopan in IgA nephropathy

Iptacopan, compared with placebo, slowed the decline in kidney function over 24 months of treatment in patients with immunoglobulin A (IgA) nephropathy while demonstrating an acceptable safety profile, according to final clinical trial data reported by Prof. Jonathan Barratt (University of Leicester, UK) [1].

APPLAUSE-IgAN (NCT04578834) was a phase 3, randomised, double-blind, placebo-controlled trial in patients with IgA nephropathy. Patients were eligible if they had biopsy-confirmed disease, a 24-hour urine protein-to-creatinine ratio (UPCR) ≥1 g/g despite optimised supportive care for at least 90 days, and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m². Patients were randomised to receive either iptacopan 200 mg twice daily or placebo for 24 months. The primary endpoint reported in the final analysis was the annualised total eGFR slope over the 24-month treatment period. In total, 238 patients in the iptacopan group and 239 patients in the placebo group were included in the analyses.

Analysis of the primary endpoint showed an annualised eGFR decline of 6.12 mL/min/1.73 m²/year in the placebo group compared with 3.10 mL/min/1.73 m²/year in the iptacopan group, corresponding to a between-group difference of 3.02 mL/min/1.73 m²/year (95% CI 2.02–4.01; P<0.001). Furthermore, the time to first occurrence of a composite kidney failure endpoint (sustained ≥30% decline in eGFR, sustained eGFR <15 mL/min/1.73 m², maintenance dialysis, kidney transplantation, or death due to kidney failure) was longer with iptacopan (HR 0.57; 95% CI 0.40–0.81; P=0.003). Regarding safety, the most common adverse events in both groups were COVID-19, upper respiratory tract infection, and nasopharyngitis, whereas hypertension occurred more frequently in the placebo group. No deaths were reported.

“We have shown that iptacopan demonstrated a significant and clinically meaningful improvement in kidney function over 2 years, and it was well-tolerated,” concluded Prof. Barratt. “These results demonstrate the clinical benefit of sustained alternative complement pathway inhibition with iptacopan in patients with IgA nephropathy.”

1. Barratt J, et al. Iptacopan achieves near-normal kidney function decline in prespecified IgA nephropathy (IgAN) patient subgroups: APPLAUSE-IgAN final data. ERA 2026, 3–6 June. Glasgow, Scotland.