Apellis and Sobi Report Positive Phase 3 VALIANT Study Results for Pegcetacoplan in C3G and IC-MPGN

Apellis Pharmaceuticals and Sobi recently shared promising results from their Phase 3 VALIANT study that investigated the systemic use of pegcetacoplan for patients suffering from rare kidney disorders, C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). These kidney diseases currently lack approved treatments, and pegcetacoplan has shown considerable efficacy in addressing them.

The study successfully met its primary goal by achieving a significant 68% reduction in proteinuria for C3G and IC-MPGN patients who were administered pegcetacoplan, compared to those who received a placebo. This result was statistically and clinically meaningful, showing consistency across various patient subsets, including different age groups and patients with both native and post-transplant kidneys.

Key secondary endpoints also saw positive outcomes. Pegcetacoplan displayed significant results in combined renal endpoints, which included proteinuria reduction and stabilization of estimated glomerular filtration rate (eGFR). The treatment also achieved a notable reduction in C3c staining on kidney biopsies, indicating histological improvement.

Dr. Carla Nester, lead principal investigator for the VALIANT study and professor of pediatric nephrology at the University of Iowa Stead Family Children's Hospital, expressed optimism about the findings. She emphasized the urgent need for effective treatments for these diseases, which often lead to kidney transplants or lifelong dialysis. The results, she noted, represent a significant advancement for the rare kidney disease community.

Jeffrey Eisele, Chief Development Officer at Apellis, echoed this sentiment, highlighting that pegcetacoplan is the first investigational therapy to demonstrate such a substantial reduction in proteinuria among C3G and IC-MPGN patients. He indicated that the company aims to present these findings to the FDA and expedite the process of making this treatment available to those affected by these debilitating conditions.

Lydia Abad-Franch, head of R&D, medical affairs, and Chief Medical Officer at Sobi, reiterated the potential of pegcetacoplan to address critical needs in patients with severe kidney conditions. She stated that Sobi remains dedicated to advancing the development of pegcetacoplan and expanding its accessibility, driven by a mission to transform the lives of those with rare diseases.

The VALIANT study also confirmed that pegcetacoplan has a favorable safety profile, consistent with previously established data. The rates of adverse events (AEs) and serious AEs were similar between pegcetacoplan and placebo groups. Importantly, there were no reported cases of meningitis or severe infections caused by encapsulated bacteria.

Following the completion of the VALIANT study, all participating patients have enrolled in the VALE long-term extension study. Apellis plans to submit a supplemental new drug application to the U.S. Food and Drug Administration by early 2025, with Sobi also planning a similar submission to the European Medicines Agency within the same timeframe. Detailed data from the study will be presented at an upcoming medical congress.

The VALIANT Phase 3 study is a comprehensive, randomized, placebo-controlled, double-blinded, multi-center trial involving 124 patients aged 12 and older with C3G or primary IC-MPGN. This large-scale study is unique in including both adolescent and adult patients with either native or post-transplant kidneys. Participants received either 1080 mg of pegcetacoplan or a placebo twice weekly for 26 weeks, followed by an open-label phase where all participants received pegcetacoplan.

C3G and primary IC-MPGN are serious kidney diseases marked by excessive C3c deposits, leading to inflammation, damage, and eventual kidney failure. These conditions often result in kidney transplants or lifelong dialysis, with a significant recurrence rate post-transplant. Approximately 5,000 individuals in the United States and up to 8,000 in Europe are estimated to be affected by these diseases.

Pegcetacoplan is designed to regulate excessive activation of the complement cascade, part of the immune system, and is being investigated for various rare diseases. It is already approved for treating paroxysmal nocturnal hemoglobinuria (PNH) in the United States, European Union, and other regions under the names EMPAVELI® and Aspaveli®. Apellis and Sobi share global co-development rights for systemic pegcetacoplan, with Sobi holding exclusive commercialization rights outside the U.S.