Sibeprenlimab-szsi (VOYXACT) slowed estimated glomerular filtration rate decline versus placebo over 24 months in adult patients with primary IgA nephropathy, according to Phase 3 VISIONARY results announced by Otsuka.
Otsuka has reported that its selective APRIL inhibitor sibeprenlimab-szsi (VOYXACT) met the key secondary endpoint of the Phase 3 VISIONARY trial, demonstrating a significant benefit in kidney-function trajectory over two years in adult patients with primary IgA nephropathy (IgAN) at risk of progression.
The data, presented in a late-breaking session at GlomCon Hawaii 2026, showed an annualized estimated glomerular filtration rate (eGFR) slope of +0.3 mL/min/1.73 m²/year with sibeprenlimab, compared with −4.2 mL/min/1.73 m²/year with placebo. The between-group difference was +4.5 mL/min/1.73 m²/year (95% CI, 3.6-5.4; P<0.0001).
According to Otsuka, the result is consistent with slowing eGFR decline to a near-physiologic rate, a therapeutic goal referenced in KDIGO guidance for most adults. However, the confidence interval around the sibeprenlimab slope ranged from a decline of 0.4 mL/min/1.73 m²/year to an improvement of 0.9 mL/min/1.73 m²/year.
At 24 months, the least-squares mean change in eGFR from baseline was +1.3 mL/min/1.73 m² with sibeprenlimab and −7.9 mL/min/1.73 m² with placebo, for a treatment difference of +9.2 mL/min/1.73 m² (95% CI, 7.1-11.4; P<0.0001). This complementary endpoint was assessed using a mixed model for repeated measures.
VISIONARY (NCT05248646) is a global, randomized, double-blind, placebo-controlled Phase 3 trial in adults with primary IgAN. Its primary endpoint was change in 24-hour urine protein-to-creatinine ratio at nine months; the trial previously demonstrated a statistically significant proteinuria reduction with sibeprenlimab compared with placebo.
Safety findings through 24 months were generally similar between treatment groups, according to the company. Overall adverse events occurred in 90.7% of sibeprenlimab-treated patients and 90.0% of placebo-treated patients. Rates of infections and infestations were 51.4% and 51.0%, respectively, while injection-site reactions occurred in 35.1% and 32.2%. Serious infections were reported less frequently with sibeprenlimab than with placebo (1.9% vs 4.0%). Otsuka reported no new safety signals.
Sibeprenlimab is a selective inhibitor of A Proliferation-Inducing Ligand (APRIL), a pathway implicated in the pathogenesis of IgAN. The therapy received FDA accelerated approval in November 2025 based on the proteinuria findings from VISIONARY. Otsuka said the completed two-year dataset supports its rolling supplemental biologics license application seeking traditional approval.
The company has not yet released a full two-year analysis, including detailed subgroup data and complete trial results; it said those findings will be presented at a future scientific meeting. Participants may continue in an open-label long-term extension study (NCT05248659).
