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Apellis to Present Positive Phase 2 NOBLE Results of Pegcetacoplan in Post-Transplant Recurrence of Primary IC-MPGN and C3G at Kidney Week

  • In as early as 12 weeks:
    • 80% of patients treated with pegcetacoplan showed a reduction in C3c staining by one or more orders of magnitude of intensity from baseline
    • 40% of patients showed zero staining intensity, indicating that C3c deposits were cleared
  • Pegcetacoplan-treated patients showed improvements across key clinical measures, including proteinuria, and stable kidney function
  • No approved treatment for IC-MPGN and C3G, rare diseases that often lead to kidney failure

WALTHAM, Mass., Oct. 17, 2023 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) and Sobi® today announced that positive results from the Phase 2 NOBLE study investigating pegcetacoplan for the treatment of post-transplant recurrence of primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) will be presented at the American Society of Nephrology (ASN) Kidney Week Annual Meeting.

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 C3c deposits were cleared.

Excessive deposition of C3 breakdown products in the kidney leads 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 center for glomerular diseases at Columbia University Irving Medical Center. “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, treatment with pegcetacoplan showed a mean reduction of proteinuria (39.2% change from baseline), which is a key marker of disease progression1, in a subgroup of patients with high baseline levels (≥1g per day). Other biomarkers also improved, including an increase in mean serum C3, reduction in mean sC5b-9, and stabilization of kidney function as measured by estimated glomerular filtration rate (eGFR). There were no discontinuations due to treatment-emergent adverse events.

“Importantly, 40% of patients showed zero C3c staining after 12 weeks, indicating that pegcetacoplan is targeting the underlying cause of the disease,” Caroline Baumal, M.D., chief medical officer, Apellis. “These results continue to strengthen our confidence in pegcetacoplan as a potential treatment for both native and post-transplant forms of these rare and serious diseases.”

The Phase 3 VALIANT study investigating pegcetacoplan in adolescent and adult patients with native and post-transplant recurrence IC-MPGN and C3G is ongoing with top-line results expected in 2024. Data from the Phase 2 DISCOVERY study investigating pegcetacoplan in patients with C3G in native kidneys was recently published in KI Reports.

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 2 NOBLE Study
The Phase 2 NOBLE study (NCT04572854) is a multicenter, open-label, randomized, controlled study designed to evaluate the efficacy and safety of pegcetacoplan in 13 adults who have post-transplant recurrence of C3G or IC-MPGN. Study participants were randomized in a 3:1 ratio to receive pegcetacoplan (IC-MPGN: n=2; C3G: n=8) or maintain standard of care (IC-MPGN: n=1; C3G: n=2) 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 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 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 3 study (NCT05067127) is a randomized, placebo-controlled, double-blinded, multi-center 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 randomized to receive 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks. Following this 26-week randomized 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.

About Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) and C3 Glomerulopathy (C3G) 
IC-MPGN and C3G are rare, debilitating kidney diseases that are estimated to affect 5,000 people in the United States and up to 8,000 in Europe.2 There are no approved therapies for the diseases, and symptoms include blood in the urine, dark foamy urine due to the presence of protein, swelling, and high blood pressure.3 Approximately 50% of people living with IC-MPGN and C3G ultimately suffer from kidney failure within five to 10 years of diagnosis.4 There are no treatments available that target the underlying complement-mediated mechanism of these diseases and prevent loss of kidney function, before or after renal transplant. Although IC-MPGN is considered a distinct disease from C3G, the underlying cause and progression of the two diseases are remarkably similar and include overactivation of the complement cascade, with excessive accumulation of C3 breakdown products in the kidney causing inflammation and damage to the organ.5-9

About Pegcetacoplan in Rare Diseases
Pegcetacoplan is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, a part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is under investigation for several rare diseases across hematology and nephrology. Pegcetacoplan is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) as EMPAVELI®/Aspaveli® in the United States, European Union, and other countries globally.

About the Apellis and Sobi Collaboration
Apellis and Sobi have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy.

About Apellis
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that combines courageous science and compassion to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two approved medicines targeting C3. These include the first-ever therapy for geographic atrophy, a leading cause of blindness around the world. With nearly additional clinical and pre-clinical programs underway, we believe we have only begun to unlock the potential of targeting C3 across many serious diseases. For more information, please visit or follow us on Twitter and LinkedIn.

Apellis Forward-Looking Statement 
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether the company’s clinical trials will be fully enrolled and completed when anticipated; whether results obtained in clinical trials will be indicative of results that will be generated in future clinical trials; whether the results of the company’s clinical trials in C3G and IC-MPGN will warrant regulatory submissions and whether systemic pegcetacoplan will receive approval for those indications from the FDA or equivalent foreign regulatory agencies when expected or at all; and any other factors discussed in the “Risk Factors” section of Apellis’ Annual Report on Form 10-K with the Securities and Exchange Commission on February 21, 2023 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Lissa Pavluk 

Meredith Kaya

1. Caravaca-Fontán F, Díaz-Encarnación M, Cabello V, et al. Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy. Nephrol Dial Transplant. 2022;37(7):1270-1280. doi:10.1093/ndt/gfab075
2. Data on file using literature consensus. 
3. Complement 3 Glomerulopathy (C3G). National Kidney Foundation Website. Accessed November 21, 2019. 
4. C3 glomerulopathy. National Institute of Health, Genetics Home Reference. Accessed November 21, 2019. 
5. Smith RJH, et al. Nat Rev Nephrol. 2019;15:129-143.
6. Pickering MC, et al. Kidney Int. 2013;84:1079-1089.
7. Cook HT, Pickering MC. J Am Soc Nephrol. 2018;29:9-12.
8. Donadelli et al. Front Immunol. 2018;9:2329.
9. Noris M, Donadelli R, Remuzzi G. Autoimmune abnormalities of the alternative complement pathway in membranoproliferative glomerulonephritis and C3 glomerulopathy. Pediatr Nephrol. 2019 Aug;34(8):1311-1323.

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