Pegcetacoplan — Drug Monograph

Brand names: Empaveli

Drug class: Other

Mechanism of Action

Pegcetacoplan is a symmetric, pegylated cyclic pentadecapeptide consisting of two identical peptide subunits joined to a linear polyethylene glycol linker. It binds complement C3 and its activation fragment C3b, acting proximally in the complement cascade to control both C3b-mediated opsonization and downstream terminal complement activation. Because it targets C3 upstream of C5, it prevents both intravascular hemolysis (via terminal complement) and the extravascular hemolysis caused by C3 opsonization of surviving PNH red cells. The PEG moiety prolongs the half-life to support subcutaneous…

FDA Indications

• Paroxysmal nocturnal hemoglobinuria (PNH) in adults (approved 2021)

Common Side Effects

• Injection site reactions
• Infections
• Diarrhea
• Abdominal pain
• Respiratory tract infection
• Viral infection
• Fatigue

Clinical Pearl

In the head-to-head PEGASUS trial, pegcetacoplan was superior to eculizumab for the primary endpoint of change in hemoglobin at week 16 (adjusted difference approximately +3.8 g/dL), largely by controlling the extravascular (C3-mediated) hemolysis that persists on C5 inhibitors. Because it blocks proximal complement, missed doses or discontinuation can precipitate severe hemolysis, so adherence to twice-weekly self-infusion is critical.

Related Therapies & Mechanisms

• Danicopan (Voydeya) — Other · PNH
• Iptacopan (Fabhalta) — Other · PNH
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other