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

STOCKHOLM, Sweden I August 8, 2024 I Sobi® (STO: SOBI) and Apellis Pharmaceuticals, Inc. (NASDAQ: APLS) have announced promising topline results from the Phase 3 VALIANT study. This study explored the efficacy of systemic pegcetacoplan in patients suffering from C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), both of which are rare kidney diseases lacking approved treatments.

The primary endpoint of the study was successfully met, with results showing a statistically significant and clinically meaningful 68% reduction in proteinuria (log-transformed ratio of urine protein-to-creatinine ratio) in patients treated with pegcetacoplan compared to those receiving a placebo, both groups also receiving background therapy at Week 26. The positive effects were seen consistently across all subgroups, including different disease types (C3G and IC-MPGN), age ranges (adolescents and adults), and kidney types (native and post-transplant).

Pegcetacoplan also achieved statistical significance in several key secondary endpoints. These included a composite renal endpoint combining proteinuria reduction and estimated glomerular filtration rate (eGFR) stabilization, as well as at least a 50% reduction in proteinuria from baseline. Additionally, the treatment showed nominal significance in reducing C3c staining on kidney biopsy and stabilizing kidney function as measured by eGFR compared to placebo.

Dr. Carla Nester, the lead principal investigator for the VALIANT study and a professor of pediatric nephrology at the University of Iowa Stead Family Children’s Hospital, expressed her enthusiasm for the results. She highlighted the urgency of finding treatments targeting the underlying causes of these diseases, noting that many patients currently face the prospect of kidney transplants or lifelong dialysis. “These positive data are a major advance for the rare kidney disease community,” she stated.

Lydia Abad-Franch, MD, Head of R&D, Medical Affairs, and Chief Medical Officer at Sobi, also commented on the findings, emphasizing their belief in pegcetacoplan’s potential to address the critical needs of patients with severe kidney conditions. “We remain committed to progressing pegcetacoplan’s development and expanding its reach,” she said.

Jeffrey Eisele, Ph.D., Chief Development Officer at Apellis, added that the results exceeded expectations and highlighted pegcetacoplan as the first investigational therapy to demonstrate a strong reduction in proteinuria in C3G and IC-MPGN. He noted their commitment to sharing the data with the FDA and working quickly to make the treatment available to patients.

The VALIANT study also showed favorable safety and tolerability for pegcetacoplan, consistent with its known profile. The rates of adverse events (AEs), serious AEs, and AEs leading to discontinuation of the study drug were similar between the pegcetacoplan and placebo groups. Notably, there were no cases of meningitis or serious infections attributed to encapsulated bacteria.

All participants who completed the VALIANT study have now enrolled in the VALE long-term extension study. Plans are in place to submit a marketing application to the European Medicines Agency (EMA) in 2025, and Apellis intends to file a supplemental new drug application with the U.S. Food and Drug Administration (FDA) early in the same year. Detailed data will be presented at a forthcoming medical congress.

The VALIANT Phase 3 study is a randomized, placebo-controlled, double-blinded, multi-center trial evaluating pegcetacoplan’s efficacy and safety in 124 patients aged 12 and older with C3G or primary IC-MPGN. It’s the largest trial conducted in these patient populations and the only one to include both adolescent and adult patients with native and post-transplant kidneys. Participants received 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks, followed by an open-label phase where all 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 primary IC-MPGN are rare, debilitating kidney diseases often leading to kidney failure. Excessive C3c deposits signal disease activity, resulting in inflammation, damage, and failure of the kidneys. About 50% of patients with these conditions face kidney failure within five to ten years of diagnosis, requiring transplants or lifelong dialysis. Two-thirds of those who receive kidney transplants experience disease recurrence. The diseases affect approximately 5,000 people in the U.S. and up to 8,000 in Europe.

Pegcetacoplan, designed to regulate the excessive activation of the complement cascade, is under investigation for various rare diseases in hematology and nephrology. It is already approved for treating paroxysmal nocturnal hemoglobinuria (PNH) in multiple regions.

Apellis and Sobi share global co-development rights for systemic pegcetacoplan, with Sobi holding exclusive ex-U.S. commercialization rights, while Apellis has exclusive U.S. commercialization rights and worldwide rights for ophthalmological applications of the drug.