Phase 2 NOBLE study of pegcetacoplan shows positive data at ERA congress

Sobi® and Apellis Pharmaceuticals, Inc. announced encouraging one-year results from the phase 2 NOBLE study examining the efficacy of systemic pegcetacoplan in treating post-transplant recurrence of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). These findings were presented during a late-breaking oral presentation at the European Renal Association (ERA) Congress in Stockholm, Sweden.

Dr. Fadi Fakhouri, the presenting author and a professor of nephrology at CHUV Lausanne, Switzerland, highlighted the rapid reduction in disease activity with pegcetacoplan treatment within 12 weeks, which was maintained over a year. The study's results offer hope for patients with post-transplant C3G and IC-MPGN, who often face disease recurrence, necessitating additional kidney transplants or dialysis. There is a significant need for treatments addressing the root cause of these diseases, and these findings are promising.

After one year of treatment with pegcetacoplan, the study showed:
- A 64% reduction in C3c staining intensity in seven patients, indicating a significant decline in disease markers.
- 55% of patients, including three with IC-MPGN, exhibited zero C3c staining, suggesting complete clearance of C3c deposits.
- Consistent with the reduction in C3c staining, seven patients also showed no inflammation as per the C3G histologic index.

Excessive C3c deposits are a marker for disease activity, leading to kidney inflammation, damage, and potentially failure. Clearing these deposits and reducing inflammation helps in kidney recovery and prolongs kidney function. Pegcetacoplan treatment also led to sustained improvements in key measures of disease, such as proteinuria, and stabilization of kidney function.

Dr. Lydia Abad-Franch, Head of R&D and Medical Affairs at Sobi, emphasized the importance of a therapeutic approach that addresses the root cause of C3G and IC-MPGN. The study’s findings reinforce the potential of pegcetacoplan to treat these severe and rare conditions effectively.

Dr. Caroline Baumal, Chief Medical Officer at Apellis, noted that the NOBLE study's data strongly indicate that pegcetacoplan targets the underlying cause of these diseases by directly focusing on C3. The ongoing Phase 3 VALIANT study aims to further evaluate pegcetacoplan's potential across all patients with these rare kidney diseases, with results expected later this year.

The phase 2 NOBLE study is a multicentre, open-label, randomized, controlled study with 13 adult participants who experienced post-transplant recurrence of C3G or IC-MPGN. Participants were randomly assigned to receive either pegcetacoplan or standard care for 12 weeks, after which all participants received pegcetacoplan until week 52. The study’s primary endpoint was the proportion of patients with a reduction in C3c staining after 12 weeks. Secondary endpoints included safety evaluations, reduction in C3c staining after 52 weeks, and a 50% reduction in proteinuria.

The VALIANT Phase 3 study evaluates pegcetacoplan's efficacy and safety in approximately 90 patients aged 12 and older with C3G or primary IC-MPGN. Participants receive pegcetacoplan or placebo twice weekly for 26 weeks, followed by a 26-week open-label phase where all receive pegcetacoplan. The primary endpoint is the log-transformed ratio of urine protein-to-creatinine ratio at week 26 compared to baseline.

C3G and IC-MPGN are rare kidney diseases marked by excessive C3c deposits, leading to inflammation, damage, and potentially kidney failure. Without treatments targeting the underlying cause, many patients experience disease recurrence post-transplant. Pegcetacoplan, designed to regulate the complement cascade's excessive activation, is under investigation for treating various rare diseases across hematology and nephrology and is approved for treating paroxysmal nocturnal hemoglobinuria (PNH).

Apellis and Sobi have a global co-development agreement for systemic pegcetacoplan, with Sobi holding exclusive commercialization rights outside the U.S., and Apellis maintaining U.S. rights and worldwide rights for ophthalmological pegcetacoplan.

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