Pegcetacoplan
Complement C3 inhibitor (PEG peptide)
Also Empaveli, Syfovre, Aspaveli, APL-2, APL2
- Evidence
- AStrong human evidence
- FDA status
- FDA approvedas of 2026-10-27
- Route
- Several routes
- Studies cited
- 1 human0 animal or cell
A drug for rare blood, kidney and eye diseases. Trials show it works, though the diseases are rare so the trials were small.
Sold for
Pegcetacoplan is a targeted complement blocker for rare blood, kidney and eye diseases, not a product with a consumer market.
Studies say
In a head-to-head trial it outperformed the previous standard drug on hemoglobin in PNH, and a placebo-controlled trial showed a large reduction in urinary protein in two rare kidney diseases, which supports an A for the approved uses.
Why grade A. The PNH approval rests on PEGASUS, a randomized open-label phase 3 trial in 80 patients comparing pegcetacoplan with eculizumab, which showed a large hemoglobin advantage at 16 weeks. The kidney approvals rest on the phase 3 VALIANT trial. The trials are small because the diseases are rare; the effects are large and on hard laboratory endpoints. 13
FDA. Approved under two brand names. Empaveli, a subcutaneous infusion, was approved in 2021 for paroxysmal nocturnal hemoglobinuria in adults and in July 2025 for C3 glomerulopathy and primary immune-complex membranoproliferative glomerulonephritis in patients 12 and older; it carries a boxed warning for serious infections with encapsulated bacteria. Syfovre, an injection into the eye, was approved in 2023 for geographic atrophy from age-related macular degeneration. 234
Written from 5 cited sources. Fact-checked 2026-10-27: 18 claims checked, 3 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Rare blood, kidney and eye diseases
- Can a US doctor prescribe it?
- Yes, FDA approved for a rare blood disease and two rare kidney diseases.
- Properly tested in people?
- Yes, in controlled trials, though small because the diseases are rare; one had 80 patients.
Evidence checklist
- Randomised controlled trial PEGASUS, VALIANT randomized trialsyes
- Human study over 100 people PEGASUS had 80 patientsno
- More than one research group Trials from the developer, Apellisno information
- Clinical outcomes, not surrogate markers Hemoglobin, transfusions, urine proteinyes
- Human safety data beyond case reports Boxed infection warning from trialsyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Pegcetacoplan is a synthetic cyclic peptide, two copies of a 15-amino-acid ring joined by a polyethylene glycol chain that keeps it in the bloodstream for days. It binds complement protein C3, the central hub of the complement system, a cascade of blood proteins that tags and destroys cells the immune system flags as foreign or damaged. Apellis Pharmaceuticals developed it. 12
The first approved use was paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired disorder in which red cells lack the proteins that protect them from complement and are destroyed in the bloodstream. Later approvals added two rare complement-driven kidney diseases and, as an eye injection, geographic atrophy, a late form of dry macular degeneration. 23
How it works
Complement can be activated by three routes, but all of them converge on C3. Earlier PNH drugs, eculizumab and ravulizumab, block C5, further down the cascade. That stops the terminal attack complex from punching holes in red cells inside blood vessels, but it leaves C3 fragments free to coat red cells, which are then removed by the spleen and liver. Many patients on C5 blockers stay anemic for this reason. By binding C3 itself, pegcetacoplan prevents both the intravascular destruction and the C3 coating, which is why it raised hemoglobin where eculizumab had not. In the kidney, blocking C3 interrupts the deposits that drive C3 glomerulopathy. 12
What human research shows
PEGASUS enrolled 80 adults with PNH who remained anemic despite at least three months of eculizumab. After a four-week period on both drugs, they were randomized to pegcetacoplan alone or to continue eculizumab for 16 weeks. The primary endpoint, change in hemoglobin, favored pegcetacoplan by about 3.8 grams per deciliter. Most pegcetacoplan patients became transfusion-free, versus a minority on eculizumab, and markers of red-cell destruction and fatigue scores improved. 1
For the kidney indications, the phase 3 VALIANT trial in patients 12 and older with C3 glomerulopathy or primary IC-MPGN showed a reduction in the urine protein-to-creatinine ratio of about 68 percent relative to placebo, with stabilization of kidney function, which the FDA cited in the July 2025 approval. 3
| Study | Model | Finding |
|---|---|---|
| PEGASUS phase 3 (Hillmen 2021) | Humans, n=80 adults with PNH anemic on eculizumab, randomized open-label active-comparator, 16 weeks | Pegcetacoplan raised hemoglobin by about 3.8 g/dL more than continued eculizumab and freed most patients from transfusions. 1 |
| VALIANT phase 3 (FDA approval basis) | Humans, n=124 aged 12 and older with C3G or primary IC-MPGN, randomized double-blind placebo-controlled, 26 weeks | About 68 percent reduction in urine protein-to-creatinine ratio versus placebo, with stable kidney function. 3 |
| Empaveli prescribing information | FDA label | Documents the approved indications, boxed infection warning, vaccination requirement and risk-management program. 2 |
Safety
Blocking C3 disables a major defense against encapsulated bacteria such as meningococcus, pneumococcus and Haemophilus influenzae. Empaveli carries a boxed warning for serious infections, is distributed through a risk-management program, and requires vaccination against these bacteria before starting. In PEGASUS the common adverse events were injection-site reactions, diarrhea, headache and fatigue; breakthrough hemolysis occurred in a few patients in each arm. 12
The eye formulation has its own risks tied to injection into the eye. In the American Academy of Ophthalmology's IRIS Registry, covering injections from 2016 to 2024, endophthalmitis (infection inside the eye) within 30 days followed 6.6 per 10,000 pegcetacoplan injections against 3.3 per 10,000 for anti-VEGF drugs, a statistically significant difference. Sixty-six reports of retinal vasculitis with pegcetacoplan were filed with the FDA's adverse event reporting system between 2020 and 2025, though spontaneous reports cannot establish incidence or causality. 45
Questions for your clinician
- Which vaccinations do I need before starting?
- How is my infection risk monitored on a complement blocker?
- How does it compare with eculizumab for my condition?
Questions people ask
How does pegcetacoplan differ from eculizumab?
Eculizumab blocks C5, late in the complement cascade, and stops red cells bursting inside blood vessels. Pegcetacoplan blocks C3, upstream, which also prevents the C3 coating that leads the spleen to remove red cells. That is why it corrected anemia in patients who were still anemic on eculizumab. 1
Why does it need vaccinations first?
The complement system is a main defense against bacteria with protective capsules, including the ones that cause meningitis. Blocking C3 removes that defense, so patients are vaccinated against meningococcus, pneumococcus and Haemophilus before starting, and carry a warning card. 2
Is Syfovre the same drug?
Same molecule, different formulation and route. Syfovre is injected into the eye to slow the growth of geographic atrophy lesions in dry macular degeneration. It has its own label and its own risks related to eye injections, including a higher endophthalmitis rate than anti-VEGF injections in a national registry. 4
Citations
- Hillmen 2021, N Engl J Med: pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria (PEGASUS) doi.org
- Apellis: Empaveli (pegcetacoplan) prescribing information, revised 2026 pi.apellis.com
- HCPLive 2025: FDA approves pegcetacoplan (Empaveli) for C3 glomerulopathy and IC-MPGN, based on VALIANT hcplive.com
- Zhang 2026, Am J Ophthalmol: endophthalmitis rates after anti-VEGF, corticosteroid implant and anti-complement injections, IRIS Registry pubmed.ncbi.nlm.nih.gov
- Chhablani 2026, Retina: retinal vasculitis events reported to FAERS with intravitreal anti-VEGF and complement inhibitor agents pubmed.ncbi.nlm.nih.gov
Updates
- 2026-10-27 safety paragraph on the eye formulation now cites the IRIS Registry endophthalmitis rate (6.6 vs 3.3 per 10,000; PMID 42472569) and FAERS retinal vasculitis reports (PMID 42627260).