Efficacy of complement inhibition with pegcetacoplan in children with C3 glomerulopathy.

backgroundC3 glomerulopathy (C3G) is a rare kidney disease due to a dysregulation of the alternative complement pathway, orphan of specific treatment. Pegcetacoplan is an inhibitor of the third complement component C3, currently on a phase III registration protocol in C3G. Here we describe our experience with the off-label use of pegcetacoplan in pediatric patients with C3G.

methodsThis retrospective, observational study evaluated the efficacy and safety of pegcetacoplan in five pediatric patients, not eligible in the registration protocol, over a 12-week treatment period. The drug was given subcutaneously, twice a week for the first month, then weekly. The change in urinary protein-to-urinary creatinine ratio (mean of three samples) was the primary endpoint. We also evaluated the changes in serum C3, albumin, sC5-b9, creatinine, and urinary erythrocytes (number/µL).

resultsAt baseline, median proteinuria/creatininuria ratio (mean of three samples) was 4.97 mg/mg (3.53-7.69), and after 12 weeks of treatment with pegcetacoplan, it decreased to less than 30% of baseline (p = 0.043) as did erythrocyturia (p = 0.043). C3 levels increased more than 600% of baseline (p = 0.043), whereas the levels of sC5-b9 decreased to normal range (p = 0.043). Three of four patients with impaired kidney function showed an improvement in eGFR. No adverse event was recorded.

conclusionsIn C3G patients, pegcetacoplan therapy improves clinical and laboratory features during a 12-week treatment. The present study, although small and with a limited follow-up, supports the use of complement-targeted therapy in C3G. Further studies with a larger number of patients and longer follow-up are needed.