Is pegcetacoplan FDA-approved, and what does the research show?

What is pegcetacoplan?

Pegcetacoplan is a man-made peptide drug that blocks part of the immune system called complement ¹. Complement is a chain, or cascade, of blood proteins; the label says pegcetacoplan "acts proximally in the complement cascade" ¹. C3 is a protein near the start of that chain ¹. The molecule is two identical peptides of fifteen amino acids, joined to the two ends of a chain of polyethylene glycol, or PEG ¹. Each peptide carries two altered building blocks, a methylated tryptophan and a short linker ¹.

Apellis Pharmaceuticals sells it as Empaveli, infused under the skin, and as Syfovre, injected into the eye ¹, ⁴, ³. Both are prescription products: Empaveli for a blood disease and two kidney diseases, Syfovre for an eye disease ¹, ³.

Is pegcetacoplan FDA-approved?

Yes, twice, as a prescription drug. FDA approved Empaveli on May 14, 2021, under NDA 215014, and Syfovre on February 17, 2023, under NDA 217171, both held by Apellis ⁴. An NDA is a new drug application, the file FDA approves before a drug is sold. Drugs@FDA lists both with marketing status "Prescription" as of November 9, 2026, the date of its data ⁴.

Empaveli's label states that it "is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)" ¹. PNH is a rare, acquired blood disease in which complement destroys red blood cells, a process called hemolysis ². FDA also approved it "for the treatment of adult and pediatric patients aged 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), to reduce proteinuria and the loss of kidney function" ¹. Those are two kidney diseases in which complement fragments are deposited in the glomeruli, the kidney's filtering units; proteinuria is protein leaking into the urine ¹.

Syfovre's label states that it "is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)" ³. Age-related macular degeneration is a disease of the macula, the center of the retina that gives sharp central vision, and it comes in a dry and a wet form. The label describes geographic atrophy as "atrophic nonexudative age-related macular degeneration," the dry form, in which patches of the retina waste away ³.

Empaveli carries a boxed warning, FDA's strongest label warning, on serious infections ¹. Because of that risk, it "is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS" ¹. A REMS is a safety program FDA requires for certain drugs. Under this one, "Prescribers must enroll in the REMS," and "Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified" ¹.

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How does pegcetacoplan work?

The label states the mechanism in one sentence: "Pegcetacoplan binds to complement protein C3 and its activation fragment C3b, thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation" ¹. C3b is the active fragment released when C3 is cleaved, and blocking both stops the chain early ¹.

In PNH, the label explains, red cells are destroyed in two ways ¹. Inside blood vessels, the membrane attack complex, the cascade's end product, breaks them; outside the vessels, cells coated with C3b are cleared ¹. Older PNH drugs such as eculizumab block C5, a protein further down the cascade ², ¹. The PEGASUS trial paper, described below, notes that C5 inhibition "cannot address extravascular hemolysis," the destruction outside the vessels ². Pegcetacoplan "acts proximally in the complement cascade controlling both" kinds of hemolysis ¹.

In the kidney diseases, the label says, pegcetacoplan decreases the deposition of C3 fragments in the glomeruli ¹. The Syfovre label gives the same C3 binding for the eye and no further mechanism ³.

What does the research show?

The main PNH trial is PEGASUS, the label's Study APL2-302, a phase 3, open-label, randomized trial ², ¹. Phase 3 means a late-stage trial; randomized means patients were assigned by chance; open-label means patient and doctor knew the treatment. It randomized 80 adults with PNH whose hemoglobin, the oxygen-carrying protein of red cells, stayed under 10.5 grams per deciliter despite at least three months of eculizumab ¹. It assigned 41 to pegcetacoplan under the skin and 39 to eculizumab by vein for 16 weeks ², ¹.

The primary measure was the change in hemoglobin from the start of the trial to week 16 ². Pegcetacoplan beat eculizumab by an adjusted mean of 3.84 grams per deciliter, with a 95 percent confidence interval, the likely range of the true difference, of 2.33 to 5.34 ², ¹. In the pegcetacoplan arm, 35 of 41 patients (85 percent) needed no transfusion during the 16 weeks, against 6 of 39 (15 percent) on eculizumab ², ¹. It was noninferior, meaning not measurably worse, on reticulocyte count, a count of young red cells, but not on lactate dehydrogenase, a marker of hemolysis ². Three patients in the pegcetacoplan arm left the randomized period because of hemolysis ¹.

A second trial, Study APL2-308, enrolled 53 adults with PNH who had taken no complement inhibitor in the previous three months ¹. It randomized 35 to pegcetacoplan and 18 to supportive care such as transfusions, for 26 weeks ¹. The label defines stabilization as a fall of no more than 1 gram per deciliter without a transfusion ¹. Hemoglobin stabilized in 30 of 35 (86 percent) on pegcetacoplan and in none of 18 on supportive care ¹. Eleven of the 18 crossed over to pegcetacoplan for falling hemoglobin ¹.

For the kidney diseases, Study APL2-C3G-310 was a randomized, double-blind, placebo-controlled trial ¹. A placebo is an inactive copy of the treatment, and double-blind means neither patients nor investigators knew who received the drug. It enrolled 124 people aged 12 and older with C3G or primary IC-MPGN, assigned equally to pegcetacoplan or placebo for 26 weeks ¹.

The main measure was the urine protein-to-creatinine ratio, protein in the urine set against creatinine, a waste product, to correct for how dilute the urine is ¹. At week 26 that ratio fell 68 percent in the pegcetacoplan group relative to placebo ¹. A composite of halved proteinuria with stable kidney function was met by 49 percent on pegcetacoplan and 3 percent on placebo ¹.

For the eye, two randomized trials, OAKS and DERBY, compared Syfovre with a sham, a pretend injection ³. They enrolled 1,258 patients aged 60 to 100 with geographic atrophy and assigned 839 to Syfovre and 419 to sham for 24 months ³. Over the 24 months, the atrophy area grew more slowly with Syfovre than with sham ³. In OAKS, growth was 22 percent slower with monthly and 18 percent slower with every-other-month injections; in DERBY, 18 and 17 percent ³. The label's efficacy table reports the lesion area measured on retinal imaging; it gives no vision measure ³.

None of these trials enrolled healthy people or measured weight, aging or athletic performance ², ¹, ³.

What are the side effects?

Empaveli's boxed warning states that it "increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B," and that "Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors" ¹. The label directs clinicians to "Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI," and adds that vaccination "does not eliminate the risk" ¹. The label allows starting sooner, with antibiotics, only when "the risks of delaying therapy with EMPAVELI outweigh the risk of developing a serious infection" ¹. The label contraindicates Empaveli, meaning it must not be given, "in patients with hypersensitivity to pegcetacoplan or to any of the excipients," the inactive ingredients, and "for initiation in patients with unresolved serious infection caused by encapsulated bacteria" ¹.

In PEGASUS, serious adverse reactions occurred in 7 of 41 (17 percent) on pegcetacoplan, the most common being infections, in 5 percent ¹. Injection-site reactions occurred in 16 of 41 (39 percent) on pegcetacoplan against 2 of 39 (5 percent) on eculizumab ¹. Diarrhea occurred in 9 (22 percent) against 1 (3 percent), while headache was less common, 3 (7 percent) against 9 (23 percent) ¹. The paper reports "no cases of meningitis in either group" ².

The label reports one death in each of three Empaveli trials ¹. In the 32-week open-label part of PEGASUS, one patient died of COVID-19 infection; in Study APL2-308, one patient (2 percent) who received Empaveli died of septic shock ¹. In the kidney trial, one patient on Empaveli died of respiratory failure from COVID-19 pneumonia, and none on placebo ¹. The label also reports anaphylaxis, a severe whole-body allergic reaction, after approval ¹. For PNH, the label directs: "Monitor any patient who discontinues EMPAVELI for at least 8 weeks to detect hemolysis and other reactions" ¹.

Syfovre is given by intravitreal injection, an injection into the jelly of the eye ³. Its label warns that "Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments" ³. Endophthalmitis is an infection inside the eye; a retinal detachment is the retina pulling away from the back of the eye. After approval, the label reports "Retinal vasculitis and/or retinal vascular occlusion," inflammation or blockage of the retina's vessels ³. The label says these cases "may occur with the first dose of SYFOVRE and may result in severe vision loss" ³.

Wet macular degeneration is the form with new leaking blood vessels. In the trials it developed by month 24 in 12 percent of monthly patients, 7 percent of every-other-month patients and 3 percent of the sham group ³. Deaths were 6.7 percent, 3.6 percent and 3.8 percent in those groups, which the label calls "consistent with the elderly study population" ³. Syfovre is contraindicated in "ocular or periocular infections," infections of the eye or around it, in "active intraocular inflammation," inflammation inside the eye, and in hypersensitivity to pegcetacoplan ³.

In sport

Pegcetacoplan is not named on the 2026 Prohibited List of WADA, the World Anti-Doping Agency, and complement inhibitors are not a listed class ⁵. The list names "PEPTIDE HORMONES, GROWTH FACTORS, RELATED SUBSTANCES, AND MIMETICS" in section S2, and pegcetacoplan is not among them ⁵.

Empaveli is given as an infusion under the skin ¹. The list's prohibited methods include, at M2.2, "Intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations" ⁵. Empaveli is given under the skin, not into a vein ¹.

What JumpstartMD offers

JumpstartMD does not prescribe pegcetacoplan. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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