How is it different from eculizumab?

Eculizumab blocks complement lower in the cascade at C5, whereas pegcetacoplan blocks at C3 (upstream). This lets pegcetacoplan address both intravascular and C3-mediated extravascular haemolysis, and in the PEGASUS trial it produced higher haemoglobin than eculizumab in patients with residual anaemia.

Why is vaccination required before starting?

Inhibiting complement weakens defence against encapsulated bacteria, particularly Neisseria meningitidis. Patients must be vaccinated against meningococcus (and typically pneumococcus and Hib) beforehand and watched closely for signs of serious infection.

Does the geographic atrophy use restore vision?

No. In OAKS and DERBY it slowed the enlargement of the atrophic lesion, an anatomical outcome; it was not shown to improve or preserve measured visual acuity, and it carries ocular risks such as endophthalmitis and wet-AMD conversion.

Is pegcetacoplan something people use for research or performance purposes?

No. It is a specialist complement inhibitor for serious diseases, administered under medical supervision, with significant infection risk. It has no legitimate use as a research or performance peptide.

EMA-approvedaka Empaveli, APL-2

Pegcetacoplan — Complete Research Guide (2026)

Last updated 2026-06-30

TL;DR

Pegcetacoplan (also known as Empaveli) is a peptide catalogued under Therapeutic Peptides (Compstatin analog (PEGylated)). It is described as: C3 complement. Documented context: PNH; GA. Neutral reference entry; EU status: EU-approved prescription medicine.

What is Pegcetacoplan?

Pegcetacoplan is a pegylated cyclic peptide that inhibits complement component C3, marketed as Empaveli (EU: Aspaveli) for subcutaneous use in paroxysmal nocturnal haemoglobinuria (PNH) and as Syfovre for intravitreal injection in geographic atrophy (GA) secondary to age-related macular degeneration. It is a fully approved prescription drug, not a research chemical: the US FDA approved the PNH indication in May 2021 and the GA indication in February 2023.

Evidence is high-quality for PNH, anchored by the randomized phase 3 PEGASUS trial against eculizumab, and phase 3 (OAKS/DERBY) for slowing GA lesion growth, though the GA benefit is anatomical rather than a demonstrated vision gain and the EMA declined the GA indication.

How does Pegcetacoplan work?

The peptide binds complement C3 and its activation fragment C3b, blocking cleavage of C3 and thereby inhibiting the complement cascade upstream of C5.

In PNH this prevents both intravascular and extravascular (C3-mediated) haemolysis of complement-sensitive red cells; the 40 kDa PEG moiety extends its half-life.

What does the research say about Pegcetacoplan?

In the phase 3 PEGASUS trial, pegcetacoplan was superior to eculizumab for raising haemoglobin at week 16 in adults with PNH and residual anaemia. ^[1]
In complement-inhibitor-naive PNH patients (PRINCE), pegcetacoplan controlled haemolysis and improved haemoglobin versus supportive care. ^[2]
In the phase 3 OAKS and DERBY trials, monthly or every-other-month intravitreal pegcetacoplan slowed the growth of geographic atrophy lesions versus sham. ^[4]

Clinical research & studies

The references below are the primary sources cited throughout this guide. Each links directly to PubMed or the regulator. Where evidence is preclinical (animal or in-vitro), that is stated rather than implied.

[1] Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria — Hillmen P et al., The New England Journal of Medicine 2021. (Phase 3 randomized controlled trial (PEGASUS))
[2] Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria — Wong RSM et al., Blood Advances 2023. (Randomized controlled trial (PRINCE))
[3] Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria — Wong RSM et al., Annals of Hematology 2022. (Clinical trial analysis)
[4] 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 — Heier JS et al., Lancet 2023. (Two phase 3 randomized controlled trials)
[5] Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin >=10 g/dL) who had received eculizumab or were naive to complement inhibitors — Panse J et al., PLoS One 2024. (Pooled clinical trial analysis)

Dosing context

This is not medical advice or a usage recommendation. Dosing figures are reported research context only, cited from the published literature.

For PNH, the approved regimen is subcutaneous infusion (typically 1080 mg twice weekly) self-administered via an infusion pump, sometimes overlapping with a prior C5 inhibitor during transition.

For GA it is given as an intravitreal injection by an ophthalmologist every 25 to 60 days; all dosing is physician-directed and outside the scope of self-experimentation.

Side effects & safety profile

Because it blocks complement, pegcetacoplan raises the risk of serious infections from encapsulated bacteria - especially Neisseria meningitidis - so meningococcal (and per label pneumococcal and Haemophilus influenzae type b) vaccination is required before starting, and patients should be monitored for early signs of infection.

Common effects in PNH include injection-site reactions, diarrhoea, and haemolysis if dosing is interrupted; abruptly stopping treatment can trigger severe haemolysis.

The intravitreal (GA) formulation carries ocular risks including endophthalmitis, retinal detachment, intraocular inflammation, and a signalled increase in neovascular (wet) AMD conversion.

Stacking & combinations

This is a hospital/specialist complement-directed therapy and is not a candidate for combination with performance or research peptides; the only clinically relevant transition is a supervised switch from a C5 inhibitor.

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Frequently asked questions

It is FDA-approved for paroxysmal nocturnal haemoglobinuria (Empaveli, given subcutaneously) and for geographic atrophy secondary to age-related macular degeneration (Syfovre, given by intravitreal injection). The EU approved the PNH indication (Aspaveli) but not the GA indication.

References

[1] Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria — Hillmen P et al., The New England Journal of Medicine 2021. PMID: 33730455. View sourceStudy: Phase 3 randomized controlled trial (PEGASUS)Pegcetacoplan was superior to eculizumab in improving haemoglobin levels in PNH patients with persistent anaemia.
[2] Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria — Wong RSM et al., Blood Advances 2023. PMID: 36848639. View sourceStudy: Randomized controlled trial (PRINCE)In treatment-naive PNH patients, pegcetacoplan controlled haemolysis and improved haemoglobin versus supportive care.
[3] Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria — Wong RSM et al., Annals of Hematology 2022. PMID: 35869170. View sourceStudy: Clinical trial analysisC3 inhibition normalized markers of intravascular and extravascular haemolysis in PNH.
[4] 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 — Heier JS et al., Lancet 2023. PMID: 37865470. View sourceStudy: Two phase 3 randomized controlled trialsIntravitreal pegcetacoplan slowed geographic atrophy lesion growth versus sham over 24 months.
[5] Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin >=10 g/dL) who had received eculizumab or were naive to complement inhibitors — Panse J et al., PLoS One 2024. PMID: 39079163. View sourceStudy: Pooled clinical trial analysisPegcetacoplan improved haematologic markers and reduced fatigue across prior-eculizumab and treatment-naive PNH patients.

This article is for educational and research purposes only. Peptides discussed here are not approved for human consumption by the FDA, EMA, or equivalent regulators outside of specific clinical contexts. Always consult a licensed medical professional before any therapeutic use.