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 lab-made cyclic peptide. It has two copies of a 15-amino-acid ring. A polyethylene glycol chain joins them and keeps the drug in the bloodstream for days. It binds complement protein C3, the central hub of the complement system. That system is a cascade of blood proteins. It 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). In this rare acquired disorder, red cells lack the proteins that protect them from complement. Complement destroys them in the bloodstream. Later approvals added two rare complement-driven kidney diseases. As an eye injection, it was also approved for geographic atrophy. This is a late form of dry macular degeneration. 23
How it works
Complement can be switched on 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 C3 fragments stay free to coat red cells. The spleen and liver then remove those cells. Many patients on C5 blockers stay anemic for this reason. Pegcetacoplan binds C3 itself, so it prevents both the destruction inside vessels and the C3 coating. That 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 stayed anemic despite at least three months of eculizumab. For four weeks they took both drugs. Then they were randomized. Some got pegcetacoplan alone. Others kept taking eculizumab. This lasted 16 weeks. The primary outcome was change in hemoglobin. It favored pegcetacoplan by about 3.8 grams per deciliter. Most patients on pegcetacoplan no longer needed transfusions. A minority on eculizumab did not need them. Signs of red-cell destruction improved. So did fatigue scores. 1
For the kidney approved uses, the phase 3 VALIANT trial enrolled patients 12 and older. They had C3 glomerulopathy or primary IC-MPGN. Urine protein-to-creatinine ratio fell by about 68 percent relative to placebo. Kidney function held steady, and the FDA cited this 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. It is sold only through a risk-management program. Patients get vaccinated against these germs first. In PEGASUS, the common adverse events were injection-site reactions, diarrhea, headache and fatigue. A few patients in each arm had breakthrough hemolysis. 12
The eye form has its own risks tied to injection into the eye. The American Academy of Ophthalmology's IRIS Registry covered injections from 2016 to 2024. Endophthalmitis (infection inside the eye) within 30 days followed 6.6 per 10,000 pegcetacoplan injections. For anti-VEGF drugs the rate was 3.3 per 10,000. The gap was significant. Sixty-six reports of retinal vasculitis with pegcetacoplan reached the FDA's adverse event reporting system between 2020 and 2025. But spontaneous reports cannot establish how often it happens or what caused it. 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. It stops red cells bursting inside blood vessels. Pegcetacoplan blocks C3, upstream. This 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. They also carry a warning card. 2
Is Syfovre the same drug?
Same molecule, different form 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 from eye injections. A national registry showed a higher endophthalmitis rate than with anti-VEGF injections. 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).