Peptide that blocks complement protein C3. Used subcutaneously in paroxysmal nocturnal hemoglobinuria (PNH) and, in the US, in some glomerulopathies, and by injection into the eye for geographic atrophy.
FDA (US): Approved (2021, Empaveli) for PNH in adults; expanded in 2025 to C3 glomerulopathy and primary IC-MPGN (age ≥12). Approved (2023, Syfovre) intravitreal for geographic atrophy due to AMD
EMA (EU): Approved (2021, Aspaveli) for PNH. Rejected (2024, Syfovre) for geographic atrophy: the EMA considered that slowing the lesions did not translate into a clinically relevant benefit for the patient
Dose
PNH (Empaveli/Aspaveli): 1,080 mg subcutaneously twice a week (FDA/EMA labels). Geographic atrophy (Syfovre, US only): 15 mg intravitreal every 25–60 days (FDA label).
Safety
Subcutaneous: risk of serious infections from encapsulated bacteria (meningococcus, pneumococcus, Haemophilus); requires prior vaccination and carries a boxed warning. Local reactions and diarrhea. Intravitreal: endophthalmitis, ocular inflammation, occlusive retinal vasculitis, and more exudative AMD. Hospital use only and under medical supervision.
Interactions
Do not combine with other complement inhibitors except in the transition described in the label.
Effect by goal · level of evidence
PNH: more hemoglobin and fewer transfusions than eculizumab
improvesHighRCT (AA)in people
+3.8 g/dL Hb
In PEGASUS (80 adults with anemia despite eculizumab), pegcetacoplan raised hemoglobin 3.84 g/dL more than eculizumab at 16 weeks; 85% no longer needed transfusions versus 15%.
In OAKS and DERBY (1,258 patients), the monthly injection reduced atrophy growth by 22% and 19% at 24 months versus sham, but increased exudative AMD (11–13% vs 2–4%).
It binds to C3, the central piece of the complement system, and slows the entire cascade. In PNH it prevents red blood cells from being destroyed, both inside and outside the vessels. In the eye it reduces the inflammatory damage that makes retinal atrophy grow.
What the evidence says
In people
PNH: more hemoglobin and fewer transfusions than eculizumab. In PEGASUS (80 adults with anemia despite eculizumab), pegcetacoplan raised hemoglobin 3.84 g/dL more than eculizumab at 16 weeks; 85% no longer needed transfusions versus 15%. PubMed 33730455
Geographic atrophy: somewhat slower lesion growth. In OAKS and DERBY (1,258 patients), the monthly injection reduced atrophy growth by 22% and 19% at 24 months versus sham, but increased exudative AMD (11–13% vs 2–4%). PubMed 37865470