Biopsy Scarring and Pegcetacoplan Response in C3G, With Carla Nester, MD

Carla Nester, MD, discusses sustained proteinuria reduction and kidney function findings through 76 weeks of pegcetacoplan treatment. Complement inhibition has moved C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) care beyond supportive therapy and nonspecific immunosuppression.

In 2025, the US Food and Drug Administration (FDA) approved pegcetacoplan (Empaveli), a C3 and C3b inhibitor, for both diseases in patients aged ≥12 years.3 With approval in place, the central clinical question has shifted to durability. Carla Nester, MD, MSA, FASN, professor of internal medicine and pediatrics and director of pediatric nephrology at University of Iowa Stead Family Children’s Hospital, served as lead principal investigator for the phase 3 VALIANT trial.

In its 26-week randomized period, pegcetacoplan reduced proteinuria by 68.1% vs placebo ( P < .0001).2 “Pegcetacoplan is the only treatment to achieve substantial and clinically meaningful effects across all key markers of disease: proteinuria, eGFR stabilization, and C3c staining,” Nester said in a statement.2 An interim analysis of VALIANT and its VALE extension, presented at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado , included 120 patients with up to 76 weeks of pegcetacoplan.

At week 76, proteinuria was 64.1% below baseline (95% CI, –71.2% to –55.2%), and the least squares mean change in estimated glomerular filtration rate (eGFR) was –1.4 mL/min/1.73 m2 (95% CI, –6.6 to 3.9).1 Results differed by baseline interstitial fibrosis and tubular atrophy (IFTA).

Patients with IFTA ≤25% (n = 94) had an eGFR change of +1.7 mL/min/1.73 m2 (95% CI, –3.9 to 7.3), compared with –11.0 mL/min/1.73 m2 (95% CI, –20.3 to –1.6) among those with IFTA of 26% to 50% (n = 23).1 Investigators concluded eGFR stabilization may be strongest in patients with less baseline fibrosis, supporting early detection and targeted treatment.1 Bradley Dixon, MD, also discussed the IFTA findings and treatment timing in a separate interview with HCPLive .

In the following interview, Carla Nester, MD, MSA, FASN, discusses how complement-targeted therapy has changed the management of C3G and IC-MPGN and what the 76-week data add to the original VALIANT findings. Q&A: Pegcetacoplan Proteinuria and eGFR Durability in C3G HCPLive: How has complement-targeted therapy changed treatment for C3G and primary IC-MPGN, and what questions about long-term disease control remain unresolved?

Carla Nester, MD, MSA, FASN: I think the beauty of what’s been happening since mid to late 2025 is this idea that we can actually target the underlying mechanism of disease, particularly for C3G and immune complex MPGN. Prior to that, we were doing lots of things that maybe helped a little bit, but it was really still classified as supportive care or had unacceptable side effects.

So this concept of having targeted therapeutics opens the door for the possibility of, first of all, a primary treatment approach with one of the newer agents, but also secondary monotherapy. Maybe we can even skinny down the number of medications that we actually use to get these patients in remission.

Because there’s no doubt that, for instance, in the pegcetacoplan study, we were able to get a lot of patients into a very nice remission of their urine protein and stabilization of their GFR. HCPLive: What was the 76-week VALIANT and VALE analysis designed to address, and what does the extended follow-up add to VALIANT?

Carla Nester, MD, MSA, FASN: The important aspect, and this is critical for us in any medication that we think about applying to patients, is we want to know that the effect is lasting. Obviously it doesn’t help if you get a urine protein reduction, but then after seven months or eight months, it’s gone.

What you really want to understand is that it’s a lasting effect, because the urine protein reduction is our surrogate for the fact that we’re going to get stabilization of the kidney filtering function. That’s the important background. If we move forward to what was presented at ASN, we have the 76-week data.

Those patients that were treated in VALIANT, those that agreed, moved over into VALE, the longer-term extension study. Now we get to see 76 weeks’ worth of treatment data for that group of patients, and the urine protein reduction in the entire group still stayed excellent. There was a 64.1% reduction in the urine protein and stabilization in the GFR in that group.

I think we logged for the entire group a –1.4 mL/min/1.73 m2 at the 76-week mark, and that’s incredibly important, because we’ve known that these patients are marching to end stage. For instance, from one of the largest epidemiology studies, RaDaR, we’re told that these patients are losing 5 mL/min/1.73 m2 of their kidney function.

So seeing this stabilization is excellent. But I’ll add on the extra piece. One of the things this particular 76-week data brought to us is that there’s clearly a difference in what happens to those patients who have less scar on their kidney biopsy versus more scar on their kidney biopsy before we start pegcetacoplan.

I think we listed that if you had ≤25% interstitial fibrosis and tubular atrophy, which is a measure of how much scarring is on the biopsy, that group of patients actually had a plus GFR, so +1.7 mL/min/1.73 m2. So not only did that less scarred group of patients have as good, even a little bit better, urine protein reduction, but they also had excellent stabilization of the GFR.

For the average clinician, what that should mean, and it certainly did for me, is that treating early is key. Using targeted therapy early feels to me, by this data, to be the right thing to do. Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

Nester reports relevant disclosures with Apellis Pharmaceuticals. References Nester CM, et al. Pegcetacoplan for 76 weeks maintains proteinuria reduction and stabilizes kidney function in C3 glomerulopathy or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN).

Abstract SA-OR054. Presented at: American Society of Nephrology Kidney Week 2026; October 22-25, 2026; Denver, CO. Apellis Pharmaceuticals.

Pivotal VALIANT results presented at Kidney Week highlight strength of pegcetacoplan treatment effect in patients with C3G/primary IC-MPGN. Published October 26, 2024. Accessed November 5, 2026. https://investors.apellis.com/node/15031 Empaveli (pegcetacoplan) injection, for subcutaneous use.

Prescribing information. Apellis Pharmaceuticals; 2025. Related to this article