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Pegcetacoplan for 52 Weeks Results in Sustained Proteinuria Reduction to Remission (≤0.5 g/g) and Normalization (≤0.2 g/g): Phase 3 VALIANT Trial: SA-OR048
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Pegcetacoplan for 52 Weeks Results in Sustained Proteinuria Reduction to Remission (≤0.5 g/g) and Normalization (≤0.2 g/g): Phase 3 VALIANT Trial: SA-OR048

Carla M. Nester, Fadi Fakhouri, Daniel P. Gale, Andrew S. Bomback, Christoph Licht, Giuseppe Remuzzi, Nicole Van De Kar, Katie Gordon, Anwesha Mukherjee, Johan Szamosi, …
Journal of the American Society of Nephrology, Vol.36(10S)
10/2025
DOI: 10.1681/ASN.2025da4gcc32

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Abstract

Background: Natural history studies report improved outcomes in C3 glomerulopathy (C3G) and primary immune complex-membranoproliferative glomerulonephritis (IC-MPGN) with proteinuria <0.88 or 1 g/g or proteinuria reduction ≥50%. In the 26-week randomized controlled period (RCP) of VALIANT (phase 3; NCT05067127), pegcetacoplan (C3/C3b inhibitor) led to significant proteinuria reduction vs placebo in C3G/primary IC-MPGN. In the following 26-week open-label period (OLP), all patients received pegcetacoplan. Methods: 59 of 63 pegcetacoplan-to-pegcetacoplan and 55 of 61 placebo-to-pegcetacoplan patients completed 52 weeks of treatment. Efficacy end points included proteinuria change from baseline. Results: At week 26, 20 (31.8%) pegcetacoplan-to-pegcetacoplan patients achieved complete remission (≤0.5 g/g); 11 (17.5%) achieved normalization (≤0.2 g/g) (Figure). Results were maintained at week 52. At week 52, 34 (54.0%) patients achieved ≥50% proteinuria reduction. Similar proportions of placebo-to-pegcetacoplan patients achieved remission and normalization compared to the pegcetacoplan group; 25 (41.0%) achieved ≥50% reduction. Conclusion: Proteinuria reductions to normalization/remission achieved in the RCP were maintained by patients who received pegcetacoplan for 52 weeks, confirming pegcetacoplan’s sustained efficacy. Consistent results were achieved in placebo-to-pegcetacoplan patients in the OLP.

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