The verdict
Our read at a glance.
Whether pegcetacoplan's approved uses are read correctly: a strong hemoglobin benefit in paroxysmal nocturnal hemoglobinuria (PNH) by blocking complement C3, versus slowing the growth of geographic atrophy lesions in the eye without a proven improvement in vision.
- The signal
- In PNH, a head-to-head trial found pegcetacoplan improved hemoglobin more than the older C5 blocker eculizumab, because it also controls the red-cell destruction those drugs leave behind. In geographic atrophy, trials showed it slows the growth of the retinal lesions compared with sham injections, but it did not show a clear benefit for actual eyesight.
- The unknown
- For the eye use, whether slowing the lesion translates into better real-world vision over time, and how to weigh that against injection risks; for PNH, long-term safety and durability and its place among the growing set of complement drugs.
- Our read
- One drug, one target (complement C3), two very different stories. In PNH the benefit is clear and it can outperform the older C5 blockers on hemoglobin. In geographic atrophy it reliably slows the retinal lesion but has not been shown to preserve eyesight, so the eye use is a textbook case of an anatomic win whose real-world payoff is still unsettled, and it carries real injection risks.
The mechanism
How it works.
The complement system is a fast-acting part of the immune system, and a protein called C3 is its central hub: once C3 is switched on, it amplifies a cascade that tags and destroys cells. Pegcetacoplan is a peptide, two small cyclic peptides attached to a PEG polymer that keeps it around longer, that binds C3 and C3b and stops that cascade at the hub. In PNH, the patient's red blood cells lack their normal complement 'shields', so complement destroys them; blocking C3 protects the cells both inside the blood vessels and in the spleen and liver, where older C5-blocking drugs leave damage behind. In geographic atrophy, overactive complement contributes to the death of retinal cells, so injecting a C3 blocker into the eye slows the spread of the damage.
Safety & regulatory boundary
The consequential part.
Blocking complement lowers defense against certain bacteria, so the PNH treatment (Empaveli) requires meningococcal and other vaccinations and carries a serious-infection risk. The eye treatment (Syfovre) is injected into the eye, with risks including eye infection, retinal detachment, conversion to 'wet' macular degeneration, and rare reports of inflammation of the retinal blood vessels. Both are prescription drugs used by specialists, for their specific approved conditions only.
What's next
What we're watching.
Long-term vision outcomes in geographic atrophy, real-world safety of the eye injections including the rare vasculitis reports, and how pegcetacoplan compares with other complement drugs in PNH.
Context
Why this is discussed.
Pegcetacoplan blocks C3, a central hub of the complement system, part of the immune system. That single target gives it more than one job: protecting red blood cells in the rare blood disease PNH (and treating a related kidney disease), and slowing the spreading retinal damage of geographic atrophy, a leading cause of vision loss in older adults.
The evidence base
14 cited references.
Regulatory & labels2
Apellis Pharmaceuticals, Inc. (FDA label) · 2025
Apellis Pharmaceuticals, Inc. (FDA label) · 2025
Registered trials3
ClinicalTrials.gov · PHASE3 · COMPLETED · 2018-08-27
ClinicalTrials.gov · PHASE2 · RECRUITING · 2025-06-23
ClinicalTrials.gov · ACTIVE_NOT_RECRUITING · 2023-09-28
Indexed literature (PubMed)9
Hillmen P et al. · N Engl J Med · 2021
Fakhouri F et al. · N Engl J Med · 2025
Heier JS et al. · Lancet · 2023
Girgis S et al. · Clin Exp Ophthalmol · 2023
Wong RSM et al. · Blood Adv · 2023
Versino F et al. · Int J Lab Hematol · 2024
Fattizzo B et al. · Blood · 2025
Panse JP et al. · Transfus Med Hemother · 2024
Hoy SM · Drugs · 2021
Keep reading