Key VALIANT Results at Kidney Week Show Pegcetacoplan's Efficacy in C3G / IC-MPGN Patients

Apellis Pharmaceuticals Inc. and Sobi® have unveiled promising results from their Phase 3 VALIANT study during the American Society of Nephrology (ASN) Kidney Week. The focus of the study is on the efficacy of pegcetacoplan in treating patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN)—two uncommon kidney diseases.

Dr. Carla Nester, the lead principal investigator, highlighted the significance of these findings, emphasizing that pegcetacoplan is the lone treatment to show noteworthy improvements across all critical markers of these diseases—proteinuria, stabilization of eGFR (a crucial kidney function measure), and reduction of C3c deposits. These conditions often affect individuals from adolescence and can result in either kidney transplants or lifelong dialysis. Therefore, the need for an effective treatment to extend kidney function is essential.

The study demonstrated a significant 68.1% reduction in proteinuria levels (p<0.0001) in patients treated with pegcetacoplan compared to a placebo, with the reduction observable by Week 4 of the treatment. This reduction was consistent across various patient subgroups, including adolescents and adults, as well as patients with native or post-transplant kidneys.

Moreover, pegcetacoplan-treated patients showed stabilization in their estimated glomerular filtration rate (eGFR) with an improvement of +6.3mL/min/1.73m2 over six months compared to those on placebo. This stabilization is a key indicator of kidney functionality. Additionally, a significant number of patients experienced a substantial decrease in C3c deposits—74.3% of those treated with pegcetacoplan saw a reduction in C3c staining intensity, while 71.4% achieved complete clearance of C3c deposits. These reductions are crucial as excessive C3c deposits can lead to kidney inflammation and damage.

Dr. Peter Hillmen from Apellis underscored the importance of these results, which highlight the potential of pegcetacoplan to improve the lives of patients by directly targeting C3, the underlying cause of C3G and IC-MPGN. All secondary endpoints of the study also favored the treatment with pegcetacoplan. The treatment showed statistical significance in composite renal endpoints, combining proteinuria reduction and eGFR stabilization, and in reducing proteinuria by at least 50% compared to baseline. The study also indicated a numerical improvement in the C3G histologic index activity score.

Throughout the 26-week randomized control period, pegcetacoplan exhibited a favorable safety profile and high compliance rates. Adverse events (AEs) were comparable between the pegcetacoplan and placebo groups, with rates of treatment-emergent AEs at 84.1% versus 93.4%, serious AEs at 9.5% versus 9.8%, severe AEs at 4.8% versus 6.6%, and AEs leading to study discontinuation at 1.6% versus 1.6%. Importantly, there were no reported cases of meningococcal meningitis or serious infections due to encapsulated bacteria.

Participants of the VALIANT study have transitioned to the VALE long-term extension study. Apellis plans to submit a supplemental new drug application to the U.S. Food and Drug Administration in early 2025, while Sobi intends to file a marketing application with the European Medicines Agency the same year.

The VALIANT Phase 3 study is the largest trial of its kind for these diseases and includes both adolescent and adult patients, with both native and post-transplant kidneys. Participants were randomized to receive pegcetacoplan or placebo twice weekly for 26 weeks, followed by a 26-week open-label phase where all patients received pegcetacoplan. The primary endpoint was the log-transformed ratio of urine protein-to-creatinine ratio (uPCR) at Week 26 compared to baseline.

C3G and IC-MPGN are rare kidney diseases marked by excessive C3c deposits, leading to kidney damage. About half of those diagnosed with these conditions progress to kidney failure within five to 10 years, necessitating a transplant or lifelong dialysis. These diseases affect approximately 5,000 individuals in the United States and up to 8,000 in Europe.

Pegcetacoplan, a targeted C3 therapy, aims to regulate excessive activation of the complement cascade, which can trigger serious diseases. It is approved for treating paroxysmal nocturnal hemoglobinuria (PNH) in various regions and is being investigated for other rare diseases in hematology and nephrology.

Apellis and Sobi share global co-development rights for systemic pegcetacoplan, with Sobi holding exclusive commercialization rights outside the U.S., and Apellis retaining rights within the U.S. and for ophthalmological applications worldwide.