Pegcetacoplan

FDA-approved complement C3 inhibitor (pegylated peptide)Established

Also known as: Empaveli, Syfovre, APL-2

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.

Calculate Dose

For research use only.

Key Facts

CAS: 2019171-69-6
Molecular Weight (MW): Approximately 43.5 kDa
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)
FDA status: Approved
Evidence level: FDA Approved
Human dose established: Yes
Administration Route: Subcutaneous infusion · Intravitreal
Frequency: Twice weekly (Empaveli); every 25 to 60 days (Syfovre)
Last updated: Oct 30, 2026
Reviewed: Oct 30, 2026
Targets: Complement C3C3b

Research summary

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.

Research evidence

Regulatory review (FDA label)3 reviewed sources
Controlled human trials5 reviewed sources
Early or uncontrolled human studies1 reviewed source
Lab & animal studies1 reviewed source

How it works

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.

Peptide Library's Pegcetacoplan profile summarises 6 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.

Pegcetacoplan dosage evidence

Pegcetacoplan has two FDA-approved products with very different doses. Empaveli is 1,080 mg by subcutaneous infusion twice weekly for adults with paroxysmal nocturnal hemoglobinuria and for people aged 12 and older with C3 glomerulopathy or primary immune-complex MPGN, with weight-based dosing for adolescents under 50 kg. Syfovre is 15 mg injected into the eye every 25 to 60 days for geographic atrophy.

FDA Approved

Dosage evidence summary for Pegcetacoplan
Human dosing established	Yes
Studied dose range	1,080 mg twice weekly under the skin (Empaveli); 15 mg into the eye every 25 to 60 days (Syfovre)
Route	Subcutaneous infusion · Intravitreal
Frequency	Twice weekly (Empaveli); every 25 to 60 days (Syfovre)
Duration studied	Continuous
Titration	None in adults. In PNH, an LDH above twice the upper limit of normal moves dosing to 1,080 mg every 3 days. Adolescents with C3G or primary IC-MPGN follow a weight schedule: from 35 kg to under 50 kg, 648 mg then 810 mg twice weekly; under 35 kg, 540 mg for two doses then 648 mg twice weekly.
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)
Evidence level	FDA Approved
Last reviewed	2026-10-30

Research-reported dosing

Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.

Research-reported dosing for Pegcetacoplan, one row per studied regimen
Study / context	Population	Dose	Route	Frequency	Duration	Outcome studied	Source
FDA label — Empaveli, PNHFDA-approved label · FDA prescribing information	Adults with paroxysmal nocturnal hemoglobinuria (PNH)	1,080 mg; 1,080 mg every 3 days if LDH exceeds twice the upper limit of normal	Subcutaneous infusion	Twice weekly	Continuous	Treatment of paroxysmal nocturnal hemoglobinuria	EMPAVELI (pegcetacoplan) injection — FDA prescribing information, DailyMed
FDA label — Empaveli, C3G and primary IC-MPGNFDA-approved label · FDA prescribing information	Adults and children aged 12 and older with C3 glomerulopathy or primary immune-complex MPGN	1,080 mg in adults and at 50 kg or more; 810 mg at 35 to under 50 kg; 648 mg under 35 kg (after the labeled first doses)	Subcutaneous infusion	Twice weekly	Continuous	Reduced proteinuria and loss of kidney function	EMPAVELI (pegcetacoplan) injection — FDA prescribing information, section 2.3, DailyMed
FDA label — SyfovreFDA-approved label · FDA prescribing information	Geographic atrophy secondary to age-related macular degeneration	15 mg (0.1 mL of 150 mg/mL) in each affected eye	Intravitreal injection by a physician	Once every 25 to 60 days	Continuous	Slower growth of geographic atrophy lesions	SYFOVRE (pegcetacoplan) injection — FDA prescribing information, DailyMed
Hillmen et al., 2021 — PEGASUS, phase 3Clinical trial · Open-label, randomised, active-controlled phase 3	Adults with PNH and hemoglobin below 10.5 g/dL despite eculizumab (41 on pegcetacoplan, 39 on eculizumab)	1,080 mg	Subcutaneous	Twice weekly	16 weeks after a 4-week run-in	Hemoglobin rose 3.84 g/dL more than with eculizumab at week 16	Hillmen P et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021.
Wong et al., 2023 — PRINCE, phase 3Clinical trial · Open-label, randomised, controlled phase 3	Complement inhibitor-naive adults with PNH (35 on pegcetacoplan, 18 on supportive care)	1,080 mg	Subcutaneous	Twice weekly	26 weeks	Hemoglobin stabilized in 85.7% versus none on supportive care	Wong RSM et al. Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2023.
Fakhouri et al., 2025 — VALIANT, phase 3Clinical trial · Randomised, double-blind, placebo-controlled phase 3	Adolescents and adults with C3 glomerulopathy or primary immune-complex MPGN, native or post-transplant (n=124)	1,080 mg, or weight-based in smaller adolescents	Subcutaneous infusion	Twice weekly	26 weeks, then 26 weeks open-label	Urine protein-to-creatinine ratio fell 68.1% relative to placebo at week 26	Fakhouri F et al. Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN. N Engl J Med. 2025.
Heier et al., 2023 — OAKS and DERBY, phase 3Clinical trial · Two randomised, double-masked, sham-controlled phase 3 trials	Adults aged 60 and older with geographic atrophy (n=1,258)	15 mg per 0.1 mL	Intravitreal	Monthly or every other month, versus sham	24 months	Lesion growth slowed by 16% to 22% versus sham at 24 months; no difference in key visual function endpoints	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.
NCT04579666 — MERIDIAN, ALS, phase 2 (not an approved use)Clinical trial · Randomised, placebo-controlled phase 2 with posted results	Adults with amyotrophic lateral sclerosis (n=249)	1,080 mg	Subcutaneous	Twice weekly	—	Terminated: did not meet its primary or key secondary efficacy endpoints at week 52	NCT04579666 — MERIDIAN: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults With Amyotrophic Lateral Sclerosis (ALS)
Roman et al., 2025 — autoimmune hemolytic anemia, phase 2 (not an approved use)Clinical trial · Open-label phase 2	Patients with cold agglutinin disease (n=13) or warm antibody autoimmune hemolytic anemia (n=11)	270 or 360 mg	Subcutaneous	Daily	Up to 48 weeks	Median hemoglobin rose 2.4 g/dL in cold agglutinin disease and 1.7 g/dL in warm antibody disease at week 48	Roman E et al. Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia. Blood. 2025.

Preclinical and analog research

Not human dosing evidence. Listed for completeness and never extrapolated to a human dose.

Research-reported dosing for Pegcetacoplan, one row per studied regimen
Study / context	Population	Dose	Route	Frequency	Duration	Outcome studied	Source
Preclinical — animal toxicologyPreclinical · Animal toxicology reported in the FDA label	Rabbits and cynomolgus monkeys	Daily doses up to 7 times the human dose; not convertible to a human dose	Subcutaneous	Daily	—	Vacuolation in renal tubules and other tissues, attributed to PEG uptake; clinical significance uncertain	EMPAVELI (pegcetacoplan) injection — FDA prescribing information, section 13.2, DailyMed

Where sources disagree

A single "pegcetacoplan dose" means nothing without naming the product. Empaveli and Syfovre differ by more than 70-fold per dose, in route, schedule and disease, and the 15–1,080 mg span is not a range to move within.
The boxed warning for serious infections and the REMS program apply to Empaveli, the systemic product. Syfovre's main risks are in the eye, including retinal vasculitis and neovascular AMD.
In DERBY, slowing of lesion growth at the 12-month primary endpoint did not reach statistical significance (p=0.062 monthly, p=0.085 every other month), while OAKS did. Both trials were significant at 24 months.
FDA's August 2026 supplement added reducing the loss of kidney function to the C3G and IC-MPGN indication. In the NEJM report of VALIANT, eGFR was not formally tested in the statistical hierarchy; the label gives a difference of 6.31 mL/min/1.73 m2 at week 26 (95% CI 0.50 to 12.12).
The label's C3G and IC-MPGN indication does not cover recurrent IC-MPGN after kidney transplant, where safety and effectiveness have not been established.
Aspaveli is the European brand of the subcutaneous product. This page covers the US labels only.

Pegcetacoplan dosage in published studies and labels →

Handling & administration

Reconstitution Guide: No reconstitution: supplied as a ready-to-use solution in single-dose vials
Injection Sites: AbdomenThighsHipsUpper arms

Sequence & molecular data

Sequence and molecular data for Pegcetacoplan
Amino acid 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 (subcutaneous)
Appearance	Clear, colorless to slightly yellowish solution in single-dose vials
Formulation	Solution
FDA UNII	TO3JYR3BOU
ChEMBL	CHEMBL4298211

Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.

Science

Mechanism of Action

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.

Origin

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

Targets

Complement C3C3b

Studies

Research statistics

246 PubMed publications · 47.3% human clinical research · 35 registered trials

Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted

Regulatory & research 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.

Regulatory and research status for Pegcetacoplan
FDA status	Approved
Research status	Approved product (see FDA status)
Availability	Prescription-Only
WADA (sport)	Unknown / Not Listed
Library classification	FDA-Approved

How FDA approval, compounding and research-only status differ

Benefits

Hemoglobin rose 3.84 g/dL more than with eculizumab at week 16 in PNH (PEGASUS)85% no longer needed transfusions, versus 15% on eculizumab (PEGASUS)Proteinuria fell 68% relative to placebo at week 26 in C3G and primary IC-MPGN (VALIANT)Geographic atrophy lesions grew 16% to 22% more slowly than with sham at 24 months (OAKS and DERBY)

Pegcetacoplan side effects

The effects below are drawn from Pegcetacoplan's prescribing information, which lists the full adverse-reaction data.

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

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

Storage & stability

This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.

Pegcetacoplan: 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. Empaveli is 1,080 mg infused under the skin twice weekly and works throughout the body. Syfovre is 15 mg injected into the eye by a physician every 25 to 60 days and acts locally. Their risks differ too.

What is the labeled dose of pegcetacoplan?

For Empaveli, the FDA label gives 1,080 mg by subcutaneous infusion twice weekly, with a weight-based schedule for adolescents under 50 kg. For Syfovre, it gives 15 mg by intravitreal injection into each affected eye every 25 to 60 days. This is reference information, not medical advice.

What are the side effects of pegcetacoplan?

With Empaveli, common effects include injection site reactions, infections and diarrhea, and a boxed warning covers serious infections from encapsulated bacteria. With Syfovre, common effects include eye discomfort, neovascular AMD, floaters and conjunctival hemorrhage. This is reference information, not medical advice.

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
External reference
SYFOVRE (pegcetacoplan) injection — FDA prescribing information, DailyMed
External reference
NDA 215014/S-012 supplement approval letter — FDA, August 2026
External reference
Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria — N Engl J Med, 2021
External reference
Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria — Blood Adv, 2023
External reference
Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN — N Engl J Med, 2025
External reference
Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY) — Lancet, 2023
External reference
Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia — Blood, 2025
External reference
From discovery to approval: A brief history of the compstatin family of complement C3 inhibitors — Clin Immunol, 2022
External reference
NCT04579666 — MERIDIAN phase 2 trial in ALS
External reference
Aspaveli — European Medicines Agency
External reference

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Compiled by Peptide Library Editorial · Reviewed Oct 30, 2026 · Updated Oct 30, 2026 · Version 1

This Pegcetacoplan profile is compiled from published literature (6 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error

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