Sibeprenlimab in IgA Nephropathy - Final Phase 3 Trial Analysis

Key numbers

• 95% confidence interval
• 95% CI

Background Sibeprenlimab, a humanized monoclonal antibody, selectively inhibits the cytokine A proliferation-inducing ligand (APRIL), a key driver of IgA nephropathy. Preliminary trial results with regard to the primary end point of the 24-hour urinary protein-to-creatinine ratio at 9 months after treatment as compared with baseline have been reported, but secondary end points, including outcomes regarding estimated glomerular filtration rate (eGFR), have not. Methods We randomly assigned adults with IgA nephropathy to receive subcutaneous sibeprenlimab (at a dose of 400 mg) or placebo every 4 weeks. The key secondary end point was the annualized slope of the eGFR over 24 months. Other secondary end points included the change in eGFR from baseline to 24 months, a composite kidney end point of kidney-function decline or kidney failure, and pharmacodynamic and safety end points. Results A total of 510 patients underwent randomization - 259 to receive sibeprenlimab and 251 to receive placebo. The annualized eGFR slope over 24 months was 0.3 ml per minute per 1.73 m2 of body-surface area per year (95% confidence interval [CI], -0.4 to 0.9) with sibeprenlimab and -4.2 ml per minute per 1.73 m2 per year (95% CI, -4.9 to -3.6) with placebo (between-group difference, 4.5 ml per minute per 1.73 m2 per year; 95% CI, 3.6 to 5.4; P<0.001). The least-squares mean treatment difference for the change in eGFR from baseline to 24 months was 9.2 ml per minute per 1.73 m2 (95% CI, 7.1 to 11.4; P<0.001). A composite kidney end-point event occurred in 1 patient (0.4%) in the sibeprenlimab group and in 28 patients (11.2%) in the placebo group (adjusted difference, -10.8 percentage points; hazard ratio, 0.029; 95% CI, 0.004 to 0.214; P<0.001). Adverse events occurred in 235 patients (90.7%) in the sibeprenlimab group and 226 patients (90.0%) in the placebo group; serious adverse events occurred in 21 patients (8.1%) and 32 patients (12.7%), respectively; and serious infections in 5 patients (1.9%) and 10 patients (4.0%). No deaths were reported. Conclusions Among patients with IgA nephropathy, treatment with sibeprenlimab stabilized the eGFR slope over 24 months, a finding consistent with a reduced risk of kidney-function decline. (Funded by Otsuka Pharmaceutical Development and Commercialization; VISIONARY ClinicalTrials.gov number, NCT05248646.).

Dana V Rizk, Jonathan Barratt, Yusuke Suzuki, Hong Zhang, Muh Geot Wong, Adrian Liew, Richard Lafayette, Vladimír Tesař, Hernán Trimarchi, Kevin Carroll, Ian S D Roberts, Vivekanand Jha, Alejandra Quevedo, Seung Hyeok Han, Rosnawati Yahya, Chee Kay Cheung, Raja Ramachandran, Michael Walsh, Bobby Chacko, Manuel Praga, Jin-Bor Chen, José Suassuna, Jing Xia, Lokesh Shah, Vlado Perkovic, VISIONARY Trial Investigators Group

Leverage2 / 5

Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).

10% of this desk’s rubric

Magnitude3 / 5

Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.

20% of this desk’s rubric

Evidence5 / 5

Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.

32% of this desk’s rubric

Novelty3 / 5

A genuinely new approach to an open problem.

8% of this desk’s rubric

Trajectory2 / 5

Some room to improve with obvious engineering.

5% of this desk’s rubric

Stakes3 / 5

Meaningful benefit to many people within a few years.

25% of this desk’s rubric

• Citations0 (reference 20, via openalex, Oct 25, 2026, 06:17 UTC)

• Reviewed by heuristic-v10 on Oct 25, 2026, 06:17 UTC. Paper type: clinical.
• Categories: Journal Article
• TOP, No.2 in the Medicine edition of October 25, 2026.