What it is
Pegcetacoplan is two short peptides held apart by a long polymer. The labels describe "two identical pentadecapeptides" — chains of 15 positions — "covalently bound to the ends of a linear 40-kiloDalton (kDa) PEG molecule." Each peptide carries two building blocks the body does not use: 1-methyl-L-tryptophan at position 4 and amino(ethoxyethoxy)acetic acid (AEEA) at position 14. The whole molecule weighs about 43.5 kDa (C1970H3848N50O947S4). By the labels' own numbers, roughly 8% of that mass is peptide and the rest is the polyethylene glycol (our arithmetic) — the PEG is there to keep the drug in circulation, or in the eye, long enough to dose it days or weeks apart.
The peptides do the binding: their target is complement protein C3.
How it works
The complement system is a cascade of blood proteins that marks cells for destruction and punches holes in them. Every route through the cascade passes C3, so blocking C3 stops it further upstream than drugs that act on C5, such as eculizumab.
- Paroxysmal nocturnal hemoglobinuria (PNH): red blood cells lack two surface proteins that normally shield them from complement. Blocking C5 stops cells bursting inside vessels, but C3 fragments still coat the cells and the liver and spleen clear them. Acting on C3 addresses both.
- C3 glomerulopathy (C3G) and primary IC-MPGN: kidney diseases in which uncontrolled complement activity deposits C3 in the kidney's filters, letting protein leak into urine.
- Geographic atrophy: the advanced dry form of age-related macular degeneration, in which patches of retina die; complement activity is implicated, and the drug is injected straight into the eye.
What the labels' trials show
| Use | Trial | Who | Result |
|---|---|---|---|
| PNH (Empaveli) | APL2-302, NCT03500549 — open-label, vs eculizumab | adults on eculizumab with Hb under 10.5 g/dL | Hb +2.37 vs −1.47 g/dL at week 16; difference 3.84 g/dL |
| C3G / IC-MPGN (Empaveli) | APL2-C3G-310 — double-blind, vs placebo | 124 patients aged 12+ | urine protein ratio 0.33 vs 1.03 of baseline at week 26; 68% reduction |
| Geographic atrophy (Syfovre) | OAKS (NCT03525613) — sham-controlled, 24 months | 202 monthly / 205 every other month / 207 sham | lesion growth −21.9% (monthly), −18.1% (every other month) |
| Geographic atrophy (Syfovre) | DERBY (NCT03525600) — sham-controlled, 24 months | 201 / 201 / 195 | −18.1%, −17.4% |
The PNH trial compared against an active drug in patients who were still anaemic on it, and was open-label. The eye trials measured lesion area by fundus autofluorescence imaging; in both, 21–31% of patients stopped treatment before month 24, and the US label reports no improvement in vision.
Safety
Empaveli carries a boxed warning: blocking complement raises the risk of serious and fatal infections with encapsulated bacteria (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type B). Vaccination is to be completed at least two weeks before the first dose unless delay is riskier, and the drug is dispensed only through the Empaveli REMS.
Syfovre's warnings are those of the eye: endophthalmitis and retinal detachment from the injection, retinal vasculitis and/or retinal vascular occlusion (which "may result in severe vision loss" and can occur with the first dose), intraocular inflammation, raised eye pressure, and new wet AMD — 12% of eyes on monthly treatment, 7% every other month, 3% on sham by month 24 (label).
Where it stands
- United States: Empaveli approved 2021-05-14 (NDA 215014) and Syfovre 2023-02-17 (NDA 217171), both Apellis Pharmaceuticals, both prescription (Drugs@FDA, 2026-10-22). Empaveli's label added C3G and primary IC-MPGN for patients aged 12 and over (label effective 2026-08-21).
- European Union, eye use: refused. The EMA recommended refusal of Syfovre on 2024-06-27 and confirmed it after re-examination on 2024-09-19 (EMA product page, read 2026-10-22).
- Research record: PubMed indexes 358 records, 33 tagged as randomised controlled trials; ClinicalTrials.gov lists 36 studies (2026-10-22).
Related reading
Pegcetacoplan is one of several approved drugs whose active part is a peptide and whose bulk is polyethylene glycol; another, for hypoparathyroidism, is palopegteriparatide (Yorvipath). For the peptide–protein line and where modified chains sit on it, see peptide vs protein, and for the basics, what peptides are.