One-Year Phase 2 Data on Pegcetacoplan for Post-Transplant C3G and IC-MPGN Presented at ERA Congress

Apellis Pharmaceuticals, Inc. and Sobi® recently revealed encouraging outcomes from their Phase 2 NOBLE study, which examined the efficacy of systemic pegcetacoplan, a targeted C3 therapy, in treating post-transplant recurrence of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). These findings were presented at the European Renal Association (ERA) Congress in Stockholm, Sweden, in May 2024.

The NOBLE study’s results have shown that pegcetacoplan can significantly reduce disease activity within 12 weeks, with these benefits being sustained for up to one year. Fadi Fakhouri, M.D., Ph.D., a professor of nephrology at CHUV in Lausanne, Switzerland, and the presentation's lead author, emphasized the importance of these findings for patients facing recurrent disease post-transplantation. These patients are at a high risk of requiring subsequent kidney transplants or dialysis, thereby underscoring the necessity for treatments targeting the disease's root cause.

In the trial, seven out of 11 patients (64%) experienced a reduction in C3c staining intensity by two or more orders of magnitude from baseline. Furthermore, six patients (55%), including all three IC-MPGN patients, displayed zero C3c staining intensity, indicating clearance of C3c deposits. The reduction in C3c staining was consistent with a decrease in kidney inflammation, as seven patients (64%) showed no inflammation based on the C3G histologic index activity score.

C3c deposits are markers of disease activity that can result in kidney inflammation and damage, eventually leading to kidney failure. Clearing these deposits and reducing inflammation can help preserve kidney function. The study also noted that pegcetacoplan led to sustained improvements in proteinuria and stabilization of kidney function.

Caroline Baumal, M.D., the chief medical officer at Apellis, highlighted that the NOBLE study's data suggest pegcetacoplan is effective in treating the underlying cause of these diseases by targeting C3. The ongoing Phase 3 VALIANT study aims to further explore pegcetacoplan's potential in a broader patient group with these rare kidney conditions.

The Phase 2 NOBLE study included 13 adults with post-transplant recurrence of C3G or IC-MPGN. Participants were randomized in a 3:1 ratio to receive pegcetacoplan or standard care for 12 weeks, followed by all participants receiving pegcetacoplan from week 13 to week 52. The primary endpoint was the proportion of patients with a reduction in C3c staining after 12 weeks of treatment. Secondary endpoints included safety evaluations, further reductions in C3c staining after 52 weeks, and a reduction in proteinuria.

The VALIANT Phase 3 study is designed to assess the efficacy and safety of pegcetacoplan in approximately 90 patients aged 12 and older, both with native kidney disease and post-transplant recurrence. Participants will be randomized to receive either pegcetacoplan or a placebo for 26 weeks, followed by a 26-week open-label phase where all patients receive pegcetacoplan. The primary endpoint is the log transformed ratio of urine protein-to-creatinine ratio (uPCR) at week 26 compared to baseline.

C3G and primary IC-MPGN are rare kidney diseases that often lead to kidney failure. Excessive C3c deposits are markers of disease activity that can cause kidney inflammation and damage. There are no current treatments targeting the underlying cause of these diseases, which affect about 5,000 people in the United States and up to 8,000 in Europe.

Pegcetacoplan is designed to regulate excessive activation of the complement cascade, a part of the immune system that can contribute to serious diseases. It is currently being investigated for various rare diseases in hematology and nephrology and is approved for treating paroxysmal nocturnal hemoglobinuria (PNH) under the brand names EMPAVELI®/Aspaveli®.

Apellis and Sobi share global co-development rights for systemic pegcetacoplan, with Sobi having exclusive commercialization rights outside the U.S. and Apellis holding exclusive U.S. rights and worldwide rights for ophthalmological pegcetacoplan. Apellis is dedicated to developing therapies for challenging diseases, while Sobi focuses on innovative treatments for rare and debilitating diseases.