Pegcetacoplan (Empaveli)

FDA-approved context Immune Support 2 sources

Pegcetacoplan is a targeted C3 therapy that regulates excessive activation of the complement cascade. It is FDA-approved for paroxysmal nocturnal hemoglobinuria (PNH) and geographic atrophy, demonstrating significant efficacy in reducing hemolysis and slowing retinal lesion growth.

01Dosing reference

Amount

1,080 mg

Frequency

Twice weekly via subcutaneous infusion

Cycle

Continuous chronic therapy

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

Binds to C3 and C3b

Pegcetacoplan specifically binds to complement protein C3 and its activation fragment C3b with high affinity.

Inhibits C3 cleavage

It prevents the cleavage of C3 into C3a and C3b, halting the downstream complement cascade.

Controls complement overactivation

This broad inhibition controls both intravascular and extravascular hemolysis in PNH and slows disease progression in geographic atrophy.

03Human evidence

Superiority to eculizumab in improving hemoglobin levels in patients with PNH.

Phase 3 PEGASUS trial involving adults with PNH and hemoglobin levels <10.5 g/dL despite eculizumab therapy.

Significant reduction in the rate of geographic atrophy lesion growth.

Phase 3 OAKS and DERBY trials involving patients with geographic atrophy secondary to age-related macular degeneration, administered via intravitreal injection.

04Preclinical evidence

Effective and sustained inhibition of the complement system.

Non-human primate models evaluating pharmacokinetics and pharmacodynamics of subcutaneous administration.

High-affinity binding to C3 and potent inhibition of alternative pathway hemolysis.

In vitro assays utilizing human serum to assess complement inhibition.

05What is known vs. unknown

Reasonably established

First FDA-approved C3-targeted therapy.
Administered via subcutaneous infusion for PNH and intravitreal injection for geographic atrophy.
Effectively addresses extravascular hemolysis, a limitation of C5 inhibitors like eculizumab.
Carries a risk of serious infections caused by encapsulated bacteria due to complement inhibition.

Unknowns & limits

Long-term safety profile regarding systemic complement inhibition and infection risk over decades.
Optimal dosing strategies and efficacy for emerging indications outside of PNH and geographic atrophy.

06Safety & regulatory context

Regulatory statusPegcetacoplan is FDA-approved as Empaveli for PNH and Syfovre for geographic atrophy. It carries a Boxed Warning for serious infections caused by encapsulated bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae). Patients must be vaccinated against these bacteria prior to starting treatment. Common side effects include injection site reactions, infections, diarrhea, and abdominal pain.

07Compared with Eculizumab (Soliris)

Pegcetacoplan (Empaveli) vs. Eculizumab (Soliris)

Key difference

Pegcetacoplan targets C3 (upstream), whereas eculizumab targets C5 (downstream). This allows pegcetacoplan to prevent extravascular hemolysis, which eculizumab cannot.

When researchers discuss each

Eculizumab is discussed as the legacy standard of care for PNH targeting C5, while pegcetacoplan is discussed when patients experience suboptimal response to C5 inhibitors due to extravascular hemolysis.

08Glossary

Paroxysmal Nocturnal Hemoglobinuria (PNH)

A rare, life-threatening blood disorder characterized by the destruction of red blood cells by the complement system.

Complement System

A part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells.

Extravascular Hemolysis

The destruction of red blood cells outside of blood vessels, typically in the spleen or liver.

09Knowledge check

Q1What is the primary target of pegcetacoplan in the complement cascade?

Q2Why does pegcetacoplan carry a Boxed Warning?

Q3Which of the following is an explicitly stated uncertainty or limitation about pegcetacoplan in the dossier?

Q4According to the dossier, in what clinical context is pegcetacoplan most often discussed versus eculizumab for PNH?

Q5Which regulatory or safety requirement related to pegcetacoplan treatment is specified in the dossier?

10Sources

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