Pivotal VALIANT Results Presented at Kidney Week Highlight Strength of Pegcetacoplan Treatment Effect in Patients with C3G / Primary IC-MPGN
Apellis Pharmaceuticals (APLS) announced positive Phase 3 VALIANT study results for pegcetacoplan in treating C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). The study demonstrated a statistically significant 68% proteinuria reduction compared to placebo. Key secondary endpoints showed pegcetacoplan stabilized kidney function (eGFR) with a +6.3mL/min/1.73m2 difference over placebo, and 71% of treated patients achieved complete clearance of C3c deposits. The treatment demonstrated a favorable safety profile, with similar adverse event rates between treatment and placebo groups. Apellis plans FDA submission in early 2025.
Apellis Pharmaceuticals (APLS) ha annunciato risultati positivi dello studio di Fase 3 VALIANT per il pegcetacoplan nel trattamento della glomerulopatia da C3 (C3G) e della glomerulonefrite membranoproliferativa da complessi immunitari primari (IC-MPGN). Lo studio ha dimostrato una riduzione della proteinuria del 68% statisticamente significativa rispetto al placebo. I principali endpoint secondari hanno mostrato che il pegcetacoplan ha stabilizzato la funzione renale (eGFR) con una differenza di +6,3 mL/min/1,73 m² rispetto al placebo, e il 71% dei pazienti trattati ha raggiunto una completa eliminazione dei depositi di C3c. Il trattamento ha dimostrato un profilo di sicurezza favorevole, con tassi di eventi avversi simili tra i gruppi di trattamento e placebo. Apellis prevede di presentare la richiesta alla FDA all'inizio del 2025.
Apellis Pharmaceuticals (APLS) anunció resultados positivos del estudio de Fase 3 VALIANT para el pegcetacoplan en el tratamiento de la glomerulopatía C3 (C3G) y la glomerulonefritis membranoproliferativa por complejos inmunitarios primarios (IC-MPGN). El estudio demostró una reducción estadísticamente significativa del 68% en la proteinuria en comparación con el placebo. Los principales resultados secundarios mostraron que el pegcetacoplan estabilizó la función renal (eGFR) con una diferencia de +6,3 mL/min/1,73 m² frente al placebo, y el 71% de los pacientes tratados logró la eliminación completa de depósitos de C3c. El tratamiento mostró un perfil de seguridad favorable, con tasas de eventos adversos similares entre los grupos de tratamiento y placebo. Apellis planea presentar su solicitud a la FDA a principios de 2025.
Apellis Pharmaceuticals (APLS)는 C3 글로머룰로파티(C3G) 및 일차 면역 복합체 막증식성 사구체신염(IC-MPGN) 치료를 위한 pegcetacoplan의 3상 VALIANT 연구 결과 긍정적임을 발표했습니다. 이 연구는 플라시보 대비 68%의 단백뇨 감소가 통계적으로 유의미하다는 결과를 보여주었습니다. 주요 이차 목표는 pegcetacoplan이 신장 기능(eGFR)을 안정시키면서 플라시보 대비 +6.3mL/min/1.73m²의 차이를 보였고, 치료를 받은 환자의 71%가 C3c 침착물이 완전히 제거됨을 확인했습니다. 치료는 안전성 프로필이 우수하며, 치료군과 플라시보 군 간에 부작용 발생률이 유사하였습니다. Apellis는 2025년 초 FDA에 제출할 계획입니다.
Apellis Pharmaceuticals (APLS) a annoncé des résultats positifs de l'étude de phase 3 VALIANT pour le pegcetacoplan dans le traitement de la glomérulopathie C3 (C3G) et de la glomérulonéphrite membranoproliférative à complexes immunitaires primaires (IC-MPGN). L'étude a montré une réduction statistiquement significative de 68% de la protéinurie par rapport au placebo. Les principaux critères secondaires ont montré que le pegcetacoplan a stabilisé la fonction rénale (eGFR) avec une différence de +6,3 mL/min/1,73 m² par rapport au placebo, et 71% des patients traités ont atteint une élimination complète des dépôts de C3c. Le traitement a démontré un profil de sécurité favorable, avec des taux d'événements indésirables similaires entre les groupes de traitement et de placebo. Apellis prévoit de soumettre une demande à la FDA début 2025.
Apellis Pharmaceuticals (APLS) hat positive Ergebnisse der Phase-3-Studie VALIANT für Pegcetacoplan bei der Behandlung der C3-Glomerulopathie (C3G) und der primären immunen komplexen membranoproliferativen Glomerulonephritis (IC-MPGN) bekannt gegeben. Die Studie zeigte eine statistisch signifikante Reduktion der Proteinurie um 68% im Vergleich zu Placebo. Wichtige sekundäre Endpunkte zeigten, dass Pegcetacoplan die Nierenfunktion (eGFR) mit einer Differenz von +6,3 mL/min/1,73 m² im Vergleich zu Placebo stabilisierte, und 71 % der behandelten Patienten erreichten eine vollständige Clearance der C3c-Ablagerungen. Die Behandlung wies ein günstiges Sicherheitsprofil auf, mit ähnlichen Raten von unerwünschten Ereignissen zwischen den Behandlungs- und Placebogruppen. Apellis plant die Einreichung bei der FDA Anfang 2025.
- Achieved 68% proteinuria reduction vs placebo (p<0.0001)
- Demonstrated eGFR stabilization with +6.3mL/min/1.73m2 difference vs placebo
- 71.4% of patients achieved complete C3c deposit clearance
- Favorable safety profile with high compliance rate
- Treatment effects observed as early as Week 4
- None.
Insights
The Phase 3 VALIANT study results demonstrate exceptional clinical efficacy for pegcetacoplan in treating C3G and IC-MPGN. The
The safety profile appears robust with comparable adverse event rates between treatment and placebo groups. Most significantly, there were no cases of meningococcal meningitis - a critical safety consideration for complement-targeting therapies. With plans for FDA submission in early 2025, pegcetacoplan could become the first approved treatment for these rare kidney diseases that typically progress to dialysis or transplantation.
These compelling Phase 3 results significantly strengthen Apellis's market position in rare diseases. With no currently approved treatments for C3G/IC-MPGN, pegcetacoplan could capture a valuable new market segment. The robust efficacy data and clean safety profile suggest high potential for regulatory approval and strong market uptake.
The timing of regulatory submissions in early 2025 for both US and EU markets positions Apellis for potential revenue expansion in 2025-2026. Given pegcetacoplan's existing approval for PNH and GA, this additional indication would leverage established manufacturing and commercialization infrastructure, potentially leading to favorable margins and market penetration.
- Statistically significant
68% (p<0.0001) proteinuria reduction compared to placebo, with reduction observed as early as Week 4
- All secondary endpoints favored treatment with pegcetacoplan, including:
- Stabilized eGFR, a key measure of kidney function
71% of patients achieved zero C3c staining intensity, demonstrating complete clearance of C3c deposits
- Results consistent across subgroups including C3G and IC-MPGN, adolescent and adult patients, and native and post-transplant kidneys
- Demonstrated favorable safety profile
WALTHAM, Mass., Oct. 26, 2024 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) and Sobi® today announced that positive results from the Phase 3 VALIANT study were presented as an oral presentation during the High-Impact Clinical Trials session at the American Society of Nephrology (ASN) Kidney Week. The results highlighted the strength of systemic pegcetacoplan treatment in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), which are rare, debilitating kidney diseases.
“These unprecedented results represent a potential breakthrough for patients living with C3G and IC-MPGN. Pegcetacoplan is the only treatment to achieve substantial and clinically meaningful effects across all key markers of disease: proteinuria, eGFR stabilization, and C3c staining,” said Carla Nester, M.D., MSA, FASN, lead principal investigator for the VALIANT study, professor of internal medicine and pediatrics, and director of pediatric nephrology, University of Iowa Stead Family Children's Hospital. “C3G and IC-MPGN affect patients as early as adolescence, often leading to either a kidney transplant or lifelong dialysis, so there is an urgent need for an approved treatment that can prolong kidney function.”
Statistically significant
Pegcetacoplan-treated patients showed a statistically significant and clinically meaningful
Pegcetacoplan stabilized eGFR and demonstrated substantial reduction in C3c staining
Patients treated with pegcetacoplan achieved stabilization of estimated glomerular filtration rate (eGFR), a key measure of kidney function, with a difference of +6.3mL/min/1.73m2 (nominal p value=0.03) over six months compared to placebo.
Additionally, a substantial proportion of patients treated with pegcetacoplan demonstrated a reduction in C3c staining intensity. Excessive C3c deposits are a key marker of disease activity, which can lead to kidney inflammation, damage, and failure.
74.3% of patients in the pegcetacoplan group and11.8% on placebo achieved a reduction in C3c staining intensity by two or more orders of magnitude from baseline, resulting in 27-fold higher odds of achieving this reduction with pegcetacoplan (nominal p value <0.0001).71.4% of pegcetacoplan-treated patients achieved zero C3c staining intensity, demonstrating complete clearance of C3c deposits.
“In the largest pivotal study in C3G and IC-MPGN, pegcetacoplan rapidly, significantly, and consistently improved key outcomes for patients with C3G and IC-MPGN,” said Peter Hillmen, M.B., Ch.B., Ph.D., chief medical advisor, rare, Apellis. “We are thrilled by these results, which underscore the potential for pegcetacoplan to significantly improve patients’ lives by directly targeting C3, the underlying cause of C3G and IC-MPGN.”
All secondary endpoints favored treatment with pegcetacoplan
In addition to the positive results on proteinuria, eGFR, and C3c staining, pegcetacoplan demonstrated statistical significance on the key secondary endpoints of composite renal endpoint, which combines proteinuria reduction and eGFR stabilization, and proteinuria reduction of at least
During the randomized, controlled 26-week treatment period, pegcetacoplan demonstrated favorable safety and tolerability, as well as a high compliance rate, consistent with its established profile. Rates of treatment-emergent adverse events (AEs) (
All patients who have already completed the VALIANT study have now enrolled into the VALE long-term extension study.
Apellis plans to submit a supplemental new drug application to the U.S. Food and Drug Administration in early 2025. Sobi plans to submit a marketing application with the European Medicines Agency in 2025.
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 124 patients who are 12 years of age and older with C3G or primary IC-MPGN. It is the largest single trial conducted in these populations and the only study to include adolescent and adult patients, with native and post-transplant kidneys. Study participants were randomized to receive pegcetacoplan or placebo twice weekly for 26 weeks. Following this 26-week randomized controlled period, patients are able to proceed to a 26-week open-label phase in which all patients receive pegcetacoplan. The primary endpoint of the study was the log transformed ratio of urine protein-to-creatinine ratio (uPCR) at Week 26 compared to baseline.
About C3 Glomerulopathy (C3G) and Primary Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
C3G and primary IC-MPGN are rare and debilitating kidney diseases that can lead to kidney failure. Excessive C3c deposits are a key marker of disease activity, which can lead to kidney inflammation, damage, and failure. There are no treatments that target the underlying cause of these diseases. Approximately
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 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. We believe we have only begun to unlock the potential of targeting C3 across serious retinal, rare, and neurological diseases. For more information, please visit http://apellis.com or follow us on X (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. These statements include, but are not limited to, statements regarding plans to submit applications for regulatory approval for the treatment of patients with C3G and IC-MPGN. 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 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 27, 2024 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.
Media:
Tracy Vineis
media@apellis.com
617-420-4839
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References
1. C3 glomerulopathy. National Institute of Health, Genetics Home Reference. https://ghr.nlm.nih.gov/condition/c3-glomerulopathy#resources. Accessed November 21, 2019.
2. Tarragón, B, et al. C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years after Transplantation. Clinical Journal of the American Society of Nephrology. August 2024; 19(8)1005-1015. doi: 10.2215/CJN.0000000000000474.
3. Data on file using literature consensus.
FAQ
What were the main results of Apellis' VALIANT Phase 3 trial for pegcetacoplan (APLS)?
When will Apellis (APLS) submit pegcetacoplan for FDA approval based on VALIANT results?
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