Key VALIANT results reveal pegcetacoplan impact on C3G/primary IC-MPGN patients

In a significant medical advancement, Sobi® and Apellis Pharmaceuticals, Inc. unveiled comprehensive data from the phase 3 VALIANT study at the 2024 American Society of Nephrology (ASN) Kidney Week. This presentation emphasized the potential benefits of systemic pegcetacoplan in treating patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), both of which are rare and challenging kidney diseases.

Carla Nester, M.D. MSA, FASN, and lead principal investigator for the VALIANT study, highlighted the significant impact of pegcetacoplan. "Pegcetacoplan is unique in providing substantial and clinically meaningful effects across all major disease markers: proteinuria, eGFR stabilization, and C3c staining," she explained. These conditions often affect individuals from adolescence, frequently leading to severe outcomes like kidney transplants or lifelong dialysis, emphasizing the urgent need for effective treatments that can extend kidney function.

The study results demonstrated a statistically significant 68% reduction in proteinuria among the pegcetacoplan-treated patients compared to the placebo group. This reduction was observed as early as Week 4 and continued through the 26-week treatment period. This effect was consistent across various patient subgroups, including adolescents, adults, those with native and post-transplant kidneys, as well as individuals with C3G and primary IC-MPGN.

Furthermore, pegcetacoplan-treated patients experienced stabilization of their estimated glomerular filtration rate (eGFR), a vital indicator of kidney health, showing a difference of +6.3 mL/min/1.73 m2 over six months compared to the placebo group. Additionally, there was a significant reduction in C3c staining intensity, a crucial marker of disease activity that can lead to kidney inflammation and damage. Notably, 71% of patients treated with pegcetacoplan achieved zero C3c staining intensity, indicating the clearance of these harmful deposits.

Lydia Abad-Franch, MD, Head of R&D, Medical Affairs, and Chief Medical Officer at Sobi, commented on the findings, noting, "C3G and primary IC-MPGN can severely impact patients' lives, often leading to kidney failure. The results presented at ASN showcase the potential of pegcetacoplan in preserving kidney function and addressing these critical unmet medical needs. We are deeply grateful to the participants, their families, and the healthcare professionals involved in this study."

The study also reported favorable safety and tolerability profiles for pegcetacoplan. During the 26-week randomized treatment period, the occurrence of adverse events was similar between the pegcetacoplan and placebo groups. The rates of treatment-emergent adverse events, serious adverse events, and severe adverse events were comparable, and there were no cases of meningococcal meningitis or serious infections attributed to encapsulated bacteria.

Patients who completed the VALIANT study are eligible to participate in the VALE long-term extension study, with Sobi planning to submit a marketing application to the European Medicines Agency in 2025. Apellis also intends to submit a supplemental new drug application to the U.S. Food and Drug Administration in early 2025.

The VALIANT phase 3 study (NCT05067127) is the largest single trial conducted in these populations, involving 124 patients aged 12 and older with C3G or primary IC-MPGN. The trial included a randomized, placebo-controlled, double-blinded, multi-center approach, with patients receiving pegcetacoplan or placebo twice weekly for 26 weeks, followed by an open-label phase where all patients received pegcetacoplan.

C3G and primary IC-MPGN are debilitating kidney diseases marked by excessive C3c deposits, leading to kidney inflammation and failure. Currently, there are no treatments targeting the root cause of these diseases, with many patients requiring kidney transplants or lifelong dialysis. The diseases affect approximately 5,000 individuals in the United States and up to 8,000 in Europe.

Pegcetacoplan, a targeted C3 therapy, is designed to regulate excessive activation of the complement cascade, a part of the immune system, and is under investigation for various rare diseases in hematology and nephrology. It is approved for treating paroxysmal nocturnal hemoglobinuria (PNH) in numerous regions.

Sobi and Apellis have global co-development rights for systemic pegcetacoplan, with Sobi holding exclusive ex-U.S. commercialization rights and Apellis holding exclusive U.S. commercialization rights and worldwide rights for ophthalmological pegcetacoplan.