Pegcetacoplan may lower proteinuria substantially in C3 glomerulopathy
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Key takeaways:
- Pegcetacoplan was associated with a 68.3% reduction in proteinuria at 26 weeks vs. placebo.
- Of patients treated with pegcetacoplan, 50.8% reached proteinuria levels below 1 g per day
SAN DIEGO — Pegcetacoplan may offer a clinical strategy to stabilize kidney function and reduce proteinuria significantly for patients with C3 glomerulopathy or primary immune complex membranoproliferative glomerulonephritis, data show.
“Probably only about anywhere from 3,000 to 5,000 [people] in the entire United States will be affected by this,” Carla M. Nester, MD, MSA, FASN, a nephrologist at the University of Iowa, Stead Family Children’s Hospital, said during a press briefing at ASN Kidney Week, “but it is a disease of the alternative pathway of complement so and up to this point, we have had absolutely no way to actually target the complement system in these patients.”
Prior to this research, “we have had absolutely no way to actually target the complement system in these patients,” Nester said.
The phase 3 VALIANT trial followed 124 patients to assess the efficacy and safety of the C3/C3b inhibitor pegcetacoplan vs. placebo. The double-blind, controlled study included adolescents aged 12 to 17 years or adults 18 years or older, with or without a previous renal transplant, who had native or post-transplant recurrent glomerulopathy, or primary immune complex membranoproliferative glomerulonephritis.
Participants in the multicenter trial were randomly selected to receive pegcetacoplan (n = 63) or placebo (n = 61) via subcutaneous infusion twice weekly for 26 weeks. The main endpoint was proteinuria reduction measured by urine protein-to-creatinine ratio at baseline vs. study end.
Pegcetacoplan was safe and effective among patients and was associated with a significant 68.3% reduction in proteinuria at 26 weeks vs. placebo, according to the researchers.
Of participants who were treated with pegcetacoplan, 50.8% reached proteinuria levels below 1 g per day. The difference in eGFR change between the pegcetacoplan and placebo group was 6.3 mL/min/1.73 m2 by the end of the trial. In addition, 71.4% of pegcetacoplan-treated patients achieved zero intensity of C3c staining.
Results were consistent across disease type, age and transplant status subgroups, Nester said. Treatment-emergent adverse events were also similar across arms.
Three serious infections occurred in the pegcetacoplan group and one in the placebo group, but none were attributed to encapsulated bacteria, according to Nester. There was one unrelated death in the pegcetacoplan arm due to COVID-19 pneumonia.
“With respect to the urine protein, another thing that affects clinicians quite significantly is that were we able to reduce these patients’ proteinuria down to a very significant level,” Nester said, “meaning, move them away from nephrotic syndrome, away from the need for additional steroids, additional hospital admissions, particularly in that pediatric group.”
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Nester CM, et al. SA-OR92. Presented at: ASN Kidney Week; Oct. 24-27, 2024; San Diego.
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