---
title: "Pegcetacoplan"
canonical_url: https://peptidelibrary.app/library/pegcetacoplan
description: "FDA-approved pegylated peptide that inhibits complement C3, sold as Empaveli for PNH, C3G and primary IC-MPGN and as Syfovre for geographic atrophy. The two products differ in dose, route and schedule."
updated: 2026-10-30
publisher: Peptide Library
notice: "Research and educational use only. Not medical advice."
---

# Pegcetacoplan

Pegcetacoplan (also called Empaveli or Syfovre) is an FDA-approved complement C3 inhibitor (pegylated peptide). Pegcetacoplan binds complement protein C3 and its activation fragment C3b, regulating C3 cleavage and the downstream steps of complement activation. Acting this far up the cascade, it controls both C3b-mediated red cell destruction outside blood vessels and terminal complement-mediated destruction inside them, which C5 inhibitors do not fully cover in PNH.

FDA-approved pegylated peptide that inhibits complement C3, sold as Empaveli for PNH, C3G and primary IC-MPGN and as Syfovre for geographic atrophy. The two products differ in dose, route and schedule.

Also known as: Empaveli, Syfovre, APL-2.

## Classification

- Type: FDA-approved complement C3 inhibitor (pegylated peptide)
- Mechanism class: Complement C3 Inhibitor
- Development stage: Approved product
- Regulatory class: FDA-approved medicine

## Mechanism

Pegcetacoplan binds complement protein C3 and its activation fragment C3b, regulating C3 cleavage and the downstream steps of complement activation. Acting this far up the cascade, it controls both C3b-mediated red cell destruction outside blood vessels and terminal complement-mediated destruction inside them, which C5 inhibitors do not fully cover in PNH. In C3G and primary IC-MPGN it reduces C3 fragment deposition in the kidney. Each molecule has two identical 15-unit peptides on a 40 kDa PEG chain.

Targets: Complement C3, C3b.

Origin: PEGylated synthetic peptide from the compstatin family of C3 inhibitors, developed by Apellis Pharmaceuticals.

## Properties

- Sequence: Two copies of Ac-Ile-Cys-Val-Trp(Me)-Gln-Asp-Trp-Gly-Ala-His-Arg-Cys-Thr-AEEA-Lys-NH2 (Cys2–Cys12 disulfide), joined to a 40 kDa PEG chain
- Molecular formula: C1970H3848N50O947S4
- Molecular weight: Approximately 43.5 kDa
- CAS number: 2019171-69-6
- Half-life: Effective half-life 8.6 days in PNH, 10.2 days in C3G and 10.8 days in primary IC-MPGN (Empaveli, subcutaneous)
- Studied routes: Subcutaneous, Intravitreal

## Evidence

- Evidence level: FDA Approved
- Highest documented: Regulatory review (FDA label)
- Human trials: 6
- Controlled human trials: 5
- Preclinical sources: 1
- Latest source: 2025

Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.

### Studies

1. EMPAVELI (pegcetacoplan) injection — FDA prescribing information, DailyMed. Regulatory label (FDA), human. Population: Adults with paroxysmal nocturnal hemoglobinuria (PNH). Treatment of paroxysmal nocturnal hemoglobinuria [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c23d89e9-b00b-4520-e053-2995a90a95af)
2. EMPAVELI (pegcetacoplan) injection — FDA prescribing information, section 2.3, DailyMed. Regulatory label (FDA), human. Population: Adults and children aged 12 and older with C3 glomerulopathy or primary immune-complex MPGN. Reduced proteinuria and loss of kidney function [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c23d89e9-b00b-4520-e053-2995a90a95af)
3. SYFOVRE (pegcetacoplan) injection — FDA prescribing information, DailyMed. Regulatory label (FDA), human. Population: Geographic atrophy secondary to age-related macular degeneration. Slower growth of geographic atrophy lesions [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b4434e61-9ec9-4e0e-bd60-45aaa0a87e64)
4. Hillmen P et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021. 2021. Controlled human trial. Population: Adults with PNH and hemoglobin below 10.5 g/dL despite eculizumab (41 on pegcetacoplan, 39 on eculizumab). Hemoglobin rose 3.84 g/dL more than with eculizumab at week 16 [Source](https://pubmed.ncbi.nlm.nih.gov/33730455/)
5. Wong RSM et al. Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2023. 2023. Controlled human trial. Population: Complement inhibitor-naive adults with PNH (35 on pegcetacoplan, 18 on supportive care). Hemoglobin stabilized in 85.7% versus none on supportive care [Source](https://pubmed.ncbi.nlm.nih.gov/36848639/)
6. Fakhouri F et al. Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN. N Engl J Med. 2025. 2025. Controlled human trial. Population: Adolescents and adults with C3 glomerulopathy or primary immune-complex MPGN, native or post-transplant (n=124). Urine protein-to-creatinine ratio fell 68.1% relative to placebo at week 26 [Source](https://pubmed.ncbi.nlm.nih.gov/41337715/)
7. Heier JS et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023. 2023. Controlled human trial. Population: Adults aged 60 and older with geographic atrophy (n=1,258). Lesion growth slowed by 16% to 22% versus sham at 24 months; no difference in key visual function endpoints [Source](https://pubmed.ncbi.nlm.nih.gov/37865470/)
8. NCT04579666 — MERIDIAN: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults With Amyotrophic Lateral Sclerosis (ALS). Controlled human trial. Population: Adults with amyotrophic lateral sclerosis (n=249). Terminated: did not meet its primary or key secondary efficacy endpoints at week 52 [Source](https://clinicaltrials.gov/study/NCT04579666)
9. Roman E et al. Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia. Blood. 2025. 2025. Human study (early or uncontrolled). Population: Patients with cold agglutinin disease (n=13) or warm antibody autoimmune hemolytic anemia (n=11). Median hemoglobin rose 2.4 g/dL in cold agglutinin disease and 1.7 g/dL in warm antibody disease at week 48 [Source](https://pubmed.ncbi.nlm.nih.gov/39486046/)
10. EMPAVELI (pegcetacoplan) injection — FDA prescribing information, section 13.2, DailyMed. Preclinical: animal or lab study. Population: Rabbits and cynomolgus monkeys. Vacuolation in renal tubules and other tissues, attributed to PEG uptake; clinical significance uncertain. Limitations: Lab or animal research: not evidence of a human effect or dose. [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c23d89e9-b00b-4520-e053-2995a90a95af)

### Registered trials

- [NCT04579666](https://clinicaltrials.gov/study/NCT04579666)

## Safety

Side effects: PNH: injection site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, fatigue; C3G and IC-MPGN: infusion site reactions, fever, nasopharyngitis, influenza, cough, nausea; Syfovre: eye discomfort, neovascular AMD, vitreous floaters, conjunctival hemorrhage.

Risks: Boxed warning (Empaveli): serious, life-threatening infections from encapsulated bacteria; vaccination at least 2 weeks before the first dose and a REMS program are required; Hemolysis after stopping treatment in PNH; the label calls for monitoring for at least 8 weeks; Hypersensitivity reactions, including anaphylaxis; Silica reagents in coagulation tests can falsely prolong aPTT; Syfovre: endophthalmitis, retinal detachment, retinal vasculitis or vascular occlusion, neovascular AMD, intraocular inflammation, raised eye pressure.

Contraindications: Hypersensitivity to pegcetacoplan or its excipients; Starting Empaveli with an unresolved serious infection caused by encapsulated bacteria; Syfovre with an ocular or periocular infection; Syfovre with active intraocular inflammation.

Human safety basis: FDA prescribing information

## Regulatory status

Pegcetacoplan is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.

- FDA status: Approved
- Availability: Prescription-Only

## Frequently asked questions

### What is pegcetacoplan?

Pegcetacoplan is a complement inhibitor made of two synthetic peptides joined to a polyethylene glycol chain. It has two US products: Empaveli, infused under the skin for blood and kidney diseases, and Syfovre, injected into the eye for a late stage of macular degeneration.

### How does pegcetacoplan work?

It binds C3 and C3b, early components of the complement system, part of the immune defenses. Blocking complement at C3 stops downstream steps that destroy red blood cells in PNH and reduces C3 deposits in the kidney in C3G and IC-MPGN. The Syfovre label describes the same C3 binding for geographic atrophy.

### Is pegcetacoplan FDA approved?

Yes. Empaveli was approved in May 2021 for adults with PNH and in July 2025 for people aged 12 and older with C3G or primary IC-MPGN. Syfovre was approved in February 2023 for geographic atrophy secondary to age-related macular degeneration.

### What is the difference between Empaveli and Syfovre?

Both contain pegcetacoplan, but they are separate products. Their risks differ too.

### What is the half-life of pegcetacoplan?

For subcutaneous Empaveli, the label gives a median effective half-life of 8.6 days in PNH, 10.2 days in C3G and 10.8 days in primary IC-MPGN. Syfovre works locally in the eye and has no comparable labeled figure.

### What compounds are similar to pegcetacoplan?

Zilucoplan is its closest relative in this library: both are peptide complement inhibitors, but zilucoplan acts at C5 and pegcetacoplan at C3. Rusfertide and motixafortide are other peptides used in blood disorders. None of them is a substitute.

## References

- [EMPAVELI (pegcetacoplan) injection — FDA prescribing information, DailyMed](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c23d89e9-b00b-4520-e053-2995a90a95af)
- [SYFOVRE (pegcetacoplan) injection — FDA prescribing information, DailyMed](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b4434e61-9ec9-4e0e-bd60-45aaa0a87e64)
- [NDA 215014/S-012 supplement approval letter — FDA, August 2026](https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/215014Orig1s012ltr.pdf)
- [Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria — N Engl J Med, 2021](https://pubmed.ncbi.nlm.nih.gov/33730455/)
- [Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria — Blood Adv, 2023](https://pubmed.ncbi.nlm.nih.gov/36848639/)
- [Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN — N Engl J Med, 2025](https://pubmed.ncbi.nlm.nih.gov/41337715/)
- [Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY) — Lancet, 2023](https://pubmed.ncbi.nlm.nih.gov/37865470/)
- [Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia — Blood, 2025](https://pubmed.ncbi.nlm.nih.gov/39486046/)
- [From discovery to approval: A brief history of the compstatin family of complement C3 inhibitors — Clin Immunol, 2022](https://pubmed.ncbi.nlm.nih.gov/34147650/)
- [NCT04579666 — MERIDIAN phase 2 trial in ALS](https://clinicaltrials.gov/study/NCT04579666)
- [Aspaveli — European Medicines Agency](https://www.ema.europa.eu/en/medicines/human/EPAR/aspaveli)

Note: Dose figures are left out of this Markdown version. See the cited sources.