Pegcetacoplan C3G data show proteinuria cut holds at 76 weeks in adolescents

DENVER: Adolescents with C3 glomerulopathy or primary IC-MPGN kept a 67.5% drop in proteinuria after 76 weeks on pegcetacoplan, investigators reported at Kidney Week 2026. The pegcetacoplan C3G data come from a post hoc analysis of 53 adolescents in the Phase 3 VALIANT trial and its open label extension, VALE. Kidney function held steady and no new safety signals appeared, the presenters said. The analysis had no placebo group after the first 26 weeks, so it cannot show how much of the long term result the drug itself caused.

What the 76 week adolescent analysis found

The pegcetacoplan C3G figures center on one measure: a 67.5% geometric mean fall in urine protein to creatinine ratio, or UPCR, from baseline at week 76. The 95% confidence interval ran from 54.1% to 77.0%. The abstract, led by Bradley P. Dixon of the University of Colorado School of Medicine, also reported a 68.4% fall at week 26 and a 69.3% fall at week 52. The investigators read the steady figures as a sign that the early response held with continued treatment. Kidney function did not decline over the same period. The least squares mean change in estimated glomerular filtration rate, or eGFR, was a gain of 8.4 mL/min/1.73 m² at week 76. Dixon discussed the results in an interview with HCPLive published on November 4.

The adolescent result sits close to the wider trial. A separate 76 week analysis of the overall VALIANT population, presented at the same meeting, showed proteinuria 64.1% below baseline with eGFR holding steady, HCPLive said. On safety, the presenters said they saw no new signals in adolescents through 76 weeks. The report did not list individual adverse events or their rates for this period, so readers cannot yet weigh the type or frequency of side effects from this abstract alone. The analysis tracked proteinuria, or protein leaking into the urine, alongside eGFR as its efficacy measures. A lasting fall in proteinuria is a marker of disease control. It is not proof that a patient will avoid kidney failure later in life.

How the VALIANT trial and VALE extension were built

VALIANT was a Phase 3, randomized, placebo controlled study in people with C3G or primary IC-MPGN. Participants were assigned 1:1 to pegcetacoplan or placebo, given as injections under the skin, for 26 weeks. A 26 week open label period followed in which everyone received the drug, and eligible participants could then join the VALE extension. In the randomized adolescent group, 55 patients aged 12 to 17 took part, 28 on pegcetacoplan and 27 on placebo. At week 26, the drug was linked to a 75% relative reduction in proteinuria against placebo, with a 95% confidence interval of 59% to 84%. Those figures come from a 2026 subgroup paper by Vivarelli and colleagues in the Clinical Journal of the American Society of Nephrology.

In the randomized phase, 71% of adolescents on pegcetacoplan reached at least a 50% cut in proteinuria, against 4% on placebo.

In the randomized phase, 71% of adolescents on pegcetacoplan reached at least a 50% cut in proteinuria, against 4% on placebo. A composite endpoint that required both that level of proteinuria reduction and no more than a 15% decline in eGFR was met by 57% of the drug group and 4% of the placebo group. The 76 week analysis worked differently. It pooled 53 adolescents who received pegcetacoplan across both studies and lined up their results by time on the drug. That meant patients first assigned to the drug were combined with those who switched over from placebo. The approach gives a longer view of people on treatment, but it removes the comparison group that made the first 26 weeks a controlled test.

Where Empaveli stands with the FDA

Pegcetacoplan is marketed in the United States as Empaveli by Apellis Pharmaceuticals. The FDA approved it on July 28, 2025, for patients aged 12 and older with C3G to reduce proteinuria, according to the agency's orphan drug designation record. The same record shows orphan designation for C3G dating to December 2018 and lists orphan exclusivity for that first indication through July 28, 2032. A second approval on August 20, 2026, widened the labeled use to reducing proteinuria and the loss of kidney function. According to HCPLive, no drug had been approved for primary IC-MPGN before that 2025 decision, and none had been cleared for teenagers with either condition. The drug is a targeted inhibitor of C3 and C3b, two central proteins in the complement cascade.

Both diseases are rare and chronic. In each, the complement system, part of the body's immune defense, is overactive and drives inflammation that can damage the kidney over time. They often appear in childhood or early adulthood. Before a complement inhibitor reached the market, care relied on supportive measures and broad immunosuppression, such as corticosteroids and mycophenolate, HCPLive reported. Dixon told the outlet that rarity can slow diagnosis, more so in adult clinics. “We in the pediatric nephrology world are more tuned into rare diseases, so we will diagnose these patients a little bit more quickly,” he said. For teenagers, long term control matters because they may live with the disease for decades after diagnosis.

What the post hoc data cannot show

The pegcetacoplan C3G analysis has clear limits. It was post hoc, meaning the question was set after the trial data existed, and it had no concurrent placebo group once the randomized period ended. As HCPLive noted, it therefore cannot establish the comparative benefit of extended treatment or show whether starting earlier prevents long term loss of kidney function. The eGFR gain of 8.4 units also carries a standard error of 4.43, which points to wide variation across a small group. Data from 53 patients are useful in a rare disease, yet they are too few to detect uncommon harms. Dixon reports relevant disclosures with Apellis Pharmaceuticals, Novartis and other companies, the outlet said. Our standards page explains how we label source types.

Dixon has argued for using complement therapy sooner. He said earlier Kidney Disease: Improving Global Outcomes guidance placed these drugs after conventional immunosuppression in severe or refractory disease. “That ultimately delays the initiation of targeted and highly effective therapies until some amount of damage has been done by uncontrolled disease activity,” he told HCPLive. The adolescent analysis did not test treatment timing, so it does not settle that debate. The next step is longer follow-up in VALE, which HCPLive said will matter for judging long term kidney outcomes. The same meeting also featured elecoglipron kidney data in type 2 diabetes. More readouts are tracked on our trials desk.

Conclusion

The pegcetacoplan C3G analysis adds 76 weeks of follow-up in 53 adolescents and shows proteinuria staying about two thirds below baseline, with stable eGFR and no new safety signals reported. The primary source is a conference abstract, reported by HCPLive, with the approval history checked against an FDA record. Because the long term data are post hoc and uncontrolled, they describe patients on treatment rather than prove added benefit. Longer VALE follow-up is the next test. This story is research news, not medical advice.