Pivotal VALIANT results presented at Kidney Week highlight strength of pegcetacoplan treatment effect in patients with C3G / Primary IC-MPGN- Sobi + Apellis

The results highlighted the potential of systemic pegcetacoplan treatment in patients with C£ glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-mpgn0 which are debilitating kidney diseases.

“These unprecedented results represent a potential breakthrough for patients living with C3G and IC-MPGN. Pegcetacoplan is the only treatment to achieve substantial and clinically meaningful effects across all key markers of disease: proteinuria, eGFR stabilization, and C3c staining,” said Carla Nester, M.D., MSA, FASN, lead principal investigator for the VALIANT study, professor of internal medicine and pediatrics, and director of pediatric nephrology, University of Iowa Stead Family Children's Hospital. “C3G and IC-MPGN affect patients as early as adolescence, often leading to either a kidney transplant or lifelong dialysis, so there is an urgent need for an approved treatment that can prolong kidney function.”

Statistically significant 68% proteinuria reduction across a broad study population, with reduction observed as early as Week 4; Pegcetacoplan-treated patients showed a statistically significant and clinically meaningful 68.1% (p<0.0001) proteinuria reduction (log-transformed ratio of urine protein-to-creatinine ratio) compared to placebo, both in addition to standard of care therapy, at Week 26. The proteinuria reduction was observed as early as Week 4 and continued through the six-month treatment period. Proteinuria reduction was consistent across broad patient subgroups including adolescent and adult patients, C3G and IC-MPGN patients, and patients with native and post-transplant kidneys.

Pegcetacoplan stabilized eGFR and demonstrated substantial reduction in C3c staining; Patients treated with pegcetacoplan achieved stabilization of estimated glomerular filtration rate (eGFR), a key measure of kidney function, with a difference of +6.3mL/min/1.73m² (nominal p value=0.03) over six months compared to placebo.

Additionally, a substantial proportion of patients treated with pegcetacoplan demonstrated a reduction in C3c staining intensity. Excessive C3c deposits are a key marker of disease activity, which can lead to kidney inflammation, damage, and failure. i. 74.3% of patients in the pegcetacoplan group and 11.8% on placebo achieved a reduction in C3c staining intensity by two or more orders of magnitude from baseline, resulting in 27-fold higher odds of achieving this reduction with pegcetacoplan (nominal p value <0.0001). ii.71.4% of pegcetacoplan-treated patients achieved zero C3c staining intensity, demonstrating complete clearance of C3c deposits.

In the largest pivotal study in C3G and IC-MPGN, pegcetacoplan rapidly, significantly, and consistently improved key outcomes for patients with C3G and IC-MPGN,” said Peter Hillmen, M.B., Ch.B., Ph.D., chief medical advisor, rare, Apellis. “We are thrilled by these results, which underscore the potential for pegcetacoplan to significantly improve patients’ lives by directly targeting C3, the underlying cause of C3G and IC-MPGN.”

All secondary endpoints favored treatment with pegcetacoplan; In addition to the positive results on proteinuria, eGFR, and C3c staining, pegcetacoplan demonstrated statistical significance on the key secondary endpoints of composite renal endpoint, which combines proteinuria reduction and eGFR stabilization, and proteinuria reduction of at least 50% compared to baseline, as well as a numerical improvement in the C3G histologic index activity score.

During the randomized, controlled 26-week treatment period, pegcetacoplan demonstrated favorable safety and tolerability, as well as a high compliance rate, consistent with its established profile. Rates of treatment-emergent adverse events (AEs) (84.1% in pegcetacoplan vs. 93.4% in placebo), serious AEs (9.5% vs. 9.8%), severe AEs (4.8 % vs. 6.6%), and AEs leading to study discontinuation (1.6% vs. 1.6%) were similar between the pegcetacoplan and placebo groups. There were no cases of meningococcal meningitis or serious infections attributed to encapsulated bacteria.

All patients who have already completed the VALIANT study have now enrolled into the VALE long-term extension study.