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VISIONARY interim results show slowing of eGFR decline with sibeprenlimab in IgA nephropathy

Compared with placebo, sibeprenlimab slowed the decline in estimated glomerular filtration rate (eGFR) in patients with biopsy-confirmed immunoglobulin A (IgA) nephropathy, according to preliminary data reported by Prof. Vlado Perkovic (University of New South Wales, Australia) [1].

VISIONARY (NCT05248646) is an ongoing, phase 3, randomised, multicentre, placebo-controlled trial of sibeprenlimab in adults with biopsy-confirmed IgA nephropathy. Patients were randomised in a 1:1 ratio to receive either sibeprenlimab 400 mg every 4 weeks or placebo for a total of 100 weeks. A prespecified interim exploratory analysis examined the annualised eGFR slope and the change in eGFR from baseline over 12 months.

At 12 months, the annualised eGFR slope was -7.6 mL/min/1.73 m2/year with placebo and -3.0 mL/min/1.73 m2/year with sibeprenlimab, corresponding to a between-group difference of 4.6 mL/min/1.73 m2/year (95% CI 2.5–6.8). Additionally, at week 48, the least-squares mean in eGFR change from baseline was -4.8 mL/min/1.73 m2 in the placebo group and 0.7 mL/min/1.73 m2 in the sibeprenlimab group, corresponding to a between-group difference of 5.5 mL/min/1.73 m2 (95% CI 3.4–7.6).

“The trial is ongoing, and these are interim analyses based on 320 patients over 12 months,” concluded Prof. Perkovic, adding that the data should be considered preliminary until the full dataset is reported. Nevertheless, he noted that these results “represent the first report of a phase 3 eGFR effect of an A Proliferation-Inducing Ligand (APRIL) inhibitor outside China, and the largest magnitude of slowing eGFR slope of any IgA nephropathy trial to date.”

  1. Perkovic V, et al. Effect of sibeprenlimab on eGFR in adults with IgA nephropathy: A prespecified interim analysis of the VISIONARY phase 3 trial. ERA 2026, 3–6 June. Glasgow, Scotland.

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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.

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ALIGN: Atrasentan preserves kidney function with long-term treatment in IgA nephropathy

Compared with placebo, atrasentan modestly slowed the decline in estimated glomerular filtration rate (eGFR) after 2.5 years of treatment in patients with immunoglobulin A (IgA) nephropathy, although it was associated with an increased risk of anaemia and fluid retention.

Prof. Hiddo J.L. Heerspink (University of Groningen, the Netherlands) presented updated results from ALIGN (NCT04573478), an ongoing randomised controlled trial comparing once-daily oral atrasentan with placebo in a 1:1 ratio for 132 weeks [1]. Patients were eligible if they had urinary protein ≥1 g/day, an eGFR ≥30 mL/min/1.73 m2, and had been receiving the maximally tolerated dose of renin–angiotensin system (RAS) inhibitors for at least 12 weeks. A separate exploratory cohort included patients receiving concomitant sodium-glucose co-transporter 2 (SGLT2) inhibitors. The key secondary endpoint presented was the change in eGFR from baseline to week 136 in the main cohort. Overall, 340 patients were randomised in the main cohort and 64 in the SGLT inhibitor stratum.

At week 136, the mean change in eGFR from baseline was -7.5 mL/min/1.73 m2 in the atrasentan group and -9.9 mL/min/1.73 m2 in the placebo group, corresponding to a between-group difference of 2.4 mL/min/1.73 m2 (95% CI -0.1 to 4.8; P=0.054). In the SGLT2 inhibitor stratum, the mean change in eGFR was -1.5 with atrasentan compared with -10.6 with placebo. Furthermore, a clinically meaningful difference was observed in the pooled population, which included both cohorts. Adverse events of special interest related to the mechanism of action of atrasentan included anaemia and fluid retention, both of which occurred more frequently with atrasentan than with placebo.

“With 2.5 years of treatment in ALIGN, the totality of the evidence shows that atrasentan leads to a clinically meaningful reduction in proteinuria and slows kidney function decline,” concluded Prof. Heerspink. “The treatment benefit with atrasentan was consistent regardless of concomitant SGLT2 inhibitor use. Overall, these findings support the use of atrasentan for the treatment of adults with IgA nephropathy.”

  1. Heerspink HJL, et al. Efficacy and safety of atrasentan treatment in participants with IgA nephropathy: 2.5-year eGFR results from the ALIGN trial. ERA 2026, 3–6 June. Glasgow, Scotland.

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