ENVISION Trial Results: Treatment for Patients With IgA Nephropathy

IgA nephropathy (IgAN) is characterized by deposition of IgA-containing circulating immune complexes (CICs) in the kidney. This pathogenesis is driven by a proliferation-inducing ligand (APRIL). The phase 2 ENVISION trial examined the effect of sibeprenlimab on patients with IgAN. Sibeprenlimab is an APRIL-neutralizing, humanized IgG2 monoclonal antibody. Results showed that sibeprenlimab demonstrated acceptable safety profile with vigorous reductions in circulating IgA and urine protein creatinine ratio (uPCR), as well as stability in estimated glomerular filtration rate (eGFR) at 12 months.

During an oral session at ASN Kidney Week 2024, Jonathan Barratt, PhD, FRCP, provided data on the effect of sibeprenlimab on change in IgA-containing CICs in patients with IgAN. The session was titled The Anti-APRIL Antibody Sibeprenlimab Reduces Circulating Immune Complexes in Patients With IgAN: The Phase 2 ENVISION Randomized Controlled Trial.

The ENVISION trial was a 12-month global, randomized trial examining the safety and effect of treatment of adults with IgAN with monthly sibeprenlimab at 2, 4, or 8 mg/kg intravenously. The exploratory endpoint of interest was the change in IgG/IgA- and IgM/IgA-CICs over time. A semi-quantitative plate-based sequential electrochemiluminescence immunoassay was used to measure serum CICs. IgG/IgA- and IgM/IgA-CICs were captured with an anti-IgA antibody and detected with ruthenylated anti-IgG or anti-IgM antibody, respectively.

Trial participants receiving sibeprenlimab had sustained, dose-dependent, reversible reductions in IgG/IgA- and IgM/IgA-CICs compared to participants in the placebo group. At 12 months, the median percent of baseline for sibeprenlimab 2 mg/kg was 81.65 for IgG/IgA-CIC and 37.05 for IgM/IgA-CIC. For sibeprenlimab 4 mg/kg and 8 mg/kg, the percents were 72.34 for IgG/IgA-CIC and 30.37 for IgM/IgA-CIC and 66.67 for IgG/IgA-CIC and 30.11 for IgM/IgA-CIC, respectively, versus 102.26 and 95.54 for placebo, respectively.

Summarizing the results, the authors said, “Sibeprenlimab demonstrated robust reduction of IgG/IgA- and IgM/IgA-CICs at all study doses. In the ENVISION trial, reduction of CICs along with galactose-deficient IgA1 and uPCR over time provide further mechanistic evidence for the effects of APRIL inhibition, resulting in stabilization of kidney function as demonstrated by reduction in proteinuria and improvement in eGFR profiles. Together, these results support the disease-modifying activity of sibeprenlimab in the treatment of IgAN.”

Source: Barratt J, Mathur M, Liew A, et al. The anti-APRIL antibody sibeprenlimab reduces circulating immune complexes in patients with IgAN: the phase 2 ENVISION randomized controlled trial. FR-OR59. Abstract of an oral session presented at the American Society of Nephrology Kidney Week 2024; October 25, 2024; San Diego, California. Funding for the study was provided by Otsuka.