Sibeprenlimab shows promise in IgA nephropathy

In the treatment of patients with IgA nephropathy, the use of sibeprenlimab, a humanized IgG2 monoclonal antibody that binds to and neutralizes a proliferation-inducing ligand (APRIL), appears to lead to a significant reduction in proteinuria, according to a phase II trial.

The trial included 155 patients with biopsy-confirmed IgA nephropathy who were at high risk for disease progression, despite having received standard-care treatment. These patients were randomly assigned to receive intravenous sibeprenlimab at a dose of 2 mg (n=38), 4 mg (n=41), or 8 mg (n=38) per kilogram of body weight or placebo (n=38). Treatment was given once monthly for 12 months.

The primary endpoint of the change from baseline in the log-transformed 24-hour urinary protein-to-creatinine ratio at month 12 was greater with sibeprenlimab than with placebo: geometric mean ratio reduction was 47.2 percent with the 2-mg dose, 58.8 percent with the 4-mg dose, 62.0 percent with the 8-mg dose, and 20.0 percent with placebo.

The least-squares mean change in the estimated glomerular filtration rate (eGFR) at month 12 was −2.7 ml/min/1.73 m² with 2 mg, 0.2 ml/min/1.73 m² with 4 mg, and −1.5 ml/min/1.73 m² with 8 mg, and −7.4 ml/min/1.73 m² with placebo.

Adverse events occurred in 78.6 of patients in the pooled sibeprenlimab groups and in 71.1 percent of those in the placebo group.