Twelve-month eGFR data from the Phase III VISIONARY trial of sibeprenlimab (Voyxact) in IgA nephropathy show that Otsuka's anti-APRIL monoclonal antibody stabilized kidney function compared to placebo. The result is likely to support sibeprenlimab's conversion of its existing accelerated approval based on proteinuria reduction, since demonstrating eGFR preservation is the confirmatory evidence needed for full FDA approval in IgA nephropathy.
The pre-specified interim analysis enrolled 320 adults with primary IgAN at risk of disease progression. At 12 months, sibeprenlimab-treated patients showed a mean eGFR change from baseline of +0.7 mL/min/1.73 m² (95% CI, –0.9 to 2.3), compared with –4.8 mL/min/1.73 m² (95% CI, –6.3 to –3.3) in the placebo arm — a treatment effect of 5.5 mL/min/1.73 m² (95% CI, 3.4 to 7.6). The annualized eGFR slope showed –3.0 mL/min/1.73 m²/year with sibeprenlimab versus –7.6 mL/min/1.73 m²/year with placebo, a treatment effect of 4.6 mL/min/1.73 m²/year. The sibeprenlimab eGFR change from baseline met the KDIGO treatment goal of limiting annual kidney function decline to below 1 mL/min/1.73 m²/year. Safety was consistent with prior data; infections (49% vs. 45%) and injection site reactions (24% vs. 23%) were the most common adverse events, with the majority mild or moderate. Otsuka has initiated a rolling supplemental Biologics License Application (sBLA) submission to the US FDA for traditional approval based on the 24-month eGFR endpoint data, which remain pending.
Sibeprenlimab selectively inhibits APRIL, blocking upstream B-cell-driven production of pathogenic galactose-deficient IgA1 without depleting B cells. The IgAN landscape now includes multiple approved agents with distinct mechanisms: Novartis' Fabhalta (iptacopan), an oral complement factor B inhibitor, reported a 49.3% slowing of eGFR slope decline over two years in the APPLAUSE-IgAN Phase III trial and has a priority review filing pending traditional approval; Vera Therapeutics' atacicept, a dual BAFF/APRIL inhibitor, has a PDUFA date of July 7, 2026 for accelerated approval. Vertex Pharmaceuticals' povetacicept, a dual BAFF/APRIL TACI-Fc fusion protein, also has a BLA under rolling review. Cross-trial comparisons are limited by differences in patient populations, background therapy, and follow-up duration. The VISIONARY 24-month final analysis, which serves as the primary confirmatory endpoint for Otsuka's traditional approval submission, will be the next key data readout.
This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/
Spot something wrong? Report an issue with this article