Positive phase II2 NOBLE results of pegcetacoplan in post-transplant recurrence of primary IC-MPGN and C3G.- Sobi + Apellis

The results showed the potential for a treatment effect in both IC-MPGN and C3G patients treated with pegcetacoplan. At Week 12, of the 10 patients (IC-MPGN: n=2; C3G: n=8) treated with pegcetacoplan: • Eight (80%) patients showed a reduction in C3c staining (reflective of damage-causing deposits) by one or more orders of magnitude of intensity from baseline. • Five (50%) patients showed a reduction in C3c staining by two or more orders of magnitude of intensity from baseline. • Four (40%) patients showed zero staining intensity, indicating that C3 deposits were cleared. Excessive deposition of C3 breakdown products in the kidney lead to inflammation and damage of the kidney, often causing kidney failure.

“In as early as 12 weeks, these positive results show that pegcetacoplan has the capacity to clear the deposits that are causing kidney damage and may block future damage from occurring,” said Andrew Bomback, M.D., presenting author and co-director of the Centre for glomerular diseases at Columbia University Irving Medical Centre. “People living with post-transplant C3G and IC-MPGN have high rates of disease recurrence, creating a significant burden on patients both physically and emotionally. These data are very promising, especially given there are no approved treatments currently available.”

Additionally, in 12 weeks pegcetacoplan showed a mean reduction of proteinuria (39.2% change from baseline), which is a key marker of disease progression ,in a subgroup of patients with high baseline levels (greater than 1g per day). Other biomarkers also improved, including an increase in mean serum C3, reduction in mean serum C5b-9 and stabilisation of kidney function, as measured by estimated glomerular filtration rate (eGFR). There were no discontinuations due to treatment-emergent adverse events.

The Phase III VALIANT study investigating pegcetacoplan in adolescent and adult patients with native and post-transplant recurrence of IC-MPGN and C3G is ongoing, with top-line results expected in 2024. Data from the Phase II DISCOVERY study investigating pegcetacoplan in patients with C3G was recently published in KI Reports. Development for pegcetacoplan for IC-MPGN and C3G is being led by Apellis.

Presentation Details at ASN Kidney Week 2023 : "Efficacy of 12-week pegcetacoplan in kidney transplant recipients with recurrent C3 glomerulopathy (C3G) or immune complex membranoproliferative glomerulonephritis (IC-MPGN)", Poster #SA-PO923 – November 4, 2023 from 10:00 a.m. – 12:00 p.m. ET .

About the Phase II NOBLE Study : The Phase II NOBLE study (NCT04572854) is a multicentre, open-label, randomised, controlled study designed to evaluate the efficacy and safety of pegcetacoplan in 13 adults who have post-transplant recurrence of C3G or primary IC-MPGN. Study participants were randomised in a 3:1 ratio to receive pegcetacoplan or maintain standard of care for 12 weeks, and patients will receive pegcetacoplan from week 13 to week 52. The primary endpoint of the study is the proportion of patients with a reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan. Secondary endpoints include an evaluation of safety, the proportion of patients with a reduction in C3c staining on renal biopsy after 52 weeks of treatment, and the proportion of patients achieving at least a 50% reduction in proteinuria.

About the VALIANT Study : The VALIANT Phase III study (NCT05067127) is a randomised, placebo-controlled, double-blinded, multicentre study designed to evaluate pegcetacoplan efficacy and safety in approximately 90 patients who are 12 years of age and older with primary IC-MPGN or C3G. It is the only study to include both native kidney patients and patients who have recurrent disease after receiving a kidney transplant. Study participants will be randomised to receive 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks. Following this 26-week randomised controlled period, patients will proceed to a 26-week open-label phase in which all patients receive pegcetacoplan. The primary endpoint of the study is the log transformed ratio of urine protein-to-creatinine ratio (uPCR) at week 26 compared to baseline. uPCR is an important indicator of kidney function.