Pegcetacoplan Beneficial for C3 Glomerulopathy, Immune-Complex MPGN

WEDNESDAY, Dec. 10, 2025 (HealthDay News) — Among patients with C3 glomerulopathy or primary immune-complex membranoproliferative glomerulonephritis (MPGN), pegcetacoplan, a C3 and C3b inhibitor, yields a significantly greater reduction in proteinuria than placebo, according to a study published in the Dec. 4 issue of the New England Journal of Medicine.

To examine the efficacy and safety of pegcetacoplan, Fadi Fakhouri, M.D., from Lausanne University Hospital in Switzerland, and colleagues conducted a phase 3 trial involving adolescents and adults with C3 glomerulopathy or primary immune-complex MPGN, including those with native kidney disease and those with disease recurrence after transplantation. A total of 124 patients were randomly assigned to receive pegcetacoplan or placebo in a 1:1 ratio.

The researchers found that the change in proteinuria was significantly greater with pegcetacoplan than placebo (geometric mean of the urinary protein-to-creatinine ratio, −67.2 versus 2.9 percent), representing a 68.1 percent relative reduction versus placebo. In hierarchical testing of five secondary end points, the pegcetacoplan group had significantly higher percentages of patients who met the composite renal end point criteria (49 versus 3 percent) and had at least a 50 percent reduction in the protein-to-creatinine ratio (60 versus 5 percent). The change in the activity score of the C3 glomerulopathy histologic index did not differ significantly between the two groups among 69 patients with evaluable kidney-biopsy samples. Compared with placebo, pegcetacoplan was not associated with more adverse events.

“We still need to follow the long-term outcomes for these patients, but the data from this trial is absolutely amazing,” lead author Carla M. Nester, M.D., from the University of Iowa in Iowa City, said in a statement.

Several authors disclosed ties to biopharmaceutical companies, including Apellis Pharmaceuticals and Sobi, which manufacture pegcetacoplan and funded the study.

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