Peptide education
Pegcetacoplan
Empaveli · Syfovre
Pegcetacoplan inhibits the complement proteins C3 and C3b. In the United States it is sold as two different prescription products: Empaveli, given under the skin for specified blood and kidney diseases, and Syfovre, injected into the eye for geographic atrophy caused by age-related macular degeneration (AMD).
The strongest evidence depends on the condition: PEGASUS measured hemoglobin in PNH, VALIANT measured protein in urine in two kidney diseases, and OAKS and DERBY measured the growth of retinal atrophy. Those outcomes answer different questions.
Overview
Quick answer
Empaveli and Syfovre share an active ingredient but have different concentrations, routes, indications, and risks. The systemic product is not an eye injection, and the eye product is not a substitute for systemic treatment.
What is Empaveli approved to treat?
Empaveli is labeled for adults with paroxysmal nocturnal hemoglobinuria (PNH). It is also labeled for adults and children aged 12 or older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), with the aim of reducing proteinuria and slowing loss of kidney function.
What is Syfovre approved to treat?
Syfovre is an eye injection for geographic atrophy secondary to AMD. Its studies measured the growth of atrophic retinal areas; they did not show a difference in key secondary visual-function endpoints at 24 months.
How do the labeled doses differ?
Empaveli's usual adult dose is 1,080 mg subcutaneously twice weekly for PNH or the listed kidney diseases; dosing for ages 12 to 17 with kidney disease depends on weight. Syfovre is 15 mg in 0.1 mL injected into each affected eye every 25 to 60 days by a qualified physician.
What is the main systemic safety warning?
Empaveli's boxed warning addresses serious infections with encapsulated bacteria. Vaccination and a restricted safety program are part of treatment, but infection can still occur after vaccination.
What eye risks are associated with Syfovre?
The label warns about infection inside the eye, retinal detachment, retinal vasculitis or vascular occlusion, and increased rates of neovascular AMD. New eye pain or changes in vision need prompt ophthalmic assessment.
Evidence
Evidence snapshot
In adults with PNH and residual anemia despite eculizumab, the adjusted change at week 16 favored pegcetacoplan over continued eculizumab.
At week 26, the urine protein-to-creatinine ratio fell more with pegcetacoplan than placebo in adolescents and adults with C3G or primary IC-MPGN.
At 12 months the primary lesion-growth result was significant in OAKS but not DERBY. Both trials showed less growth with treatment at 24 months.
The eye trials reported no difference in their key secondary visual-function endpoints at 24 months.
Empaveli carries a boxed infection warning; Syfovre has ocular warnings, including retinal vasculitis and neovascular AMD.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Empaveli can improve outcomes in PNH and selected complement-related kidney diseases. | PEGASUS found a greater increase in hemoglobin than continued eculizumab in adults with residual anemia. VALIANT found a larger reduction in urine protein than placebo in C3G and primary IC-MPGN. | Pegcetacoplan binds C3 and C3b, reducing downstream complement activation. | Supported for the populations described in the product label and the respective studies. The two trials measured different outcomes. |
| Syfovre restores vision because it slows atrophy growth. | OAKS and DERBY measured the growth of retinal atrophy. At 24 months, their key secondary visual-function endpoints did not differ between treatment and sham. | Slower lesion growth is not evidence that lost vision is restored. | |
| The two pegcetacoplan products can be exchanged by changing the amount. | Empaveli is formulated for subcutaneous administration; Syfovre is a separate intravitreal product administered by a qualified physician. | No. Each product has its own route, concentration, indication, and safety requirements. | |
| Vaccination removes the infection risk from Empaveli. | The boxed warning says serious infections from encapsulated bacteria can occur in patients receiving complement inhibitors even after vaccination. | Vaccination is a safeguard, not a guarantee against serious infection. |
Bottom line
Main takeaway
Empaveli is given under the skin for specified blood and kidney conditions; Syfovre is given into the eye for geographic atrophy.
The systemic product has a boxed infection warning, while the eye product has its own retinal and injection-related risks.
Hemoglobin, proteinuria, and retinal lesion growth come from separate trials in different populations.
Identity
What it is
Pegcetacoplan consists of two peptide components linked to polyethylene glycol. Binding C3 and C3b alters complement activation upstream of the terminal complex.
Empaveli treats adult PNH and C3G or primary IC-MPGN in patients aged 12 and older. Syfovre treats geographic atrophy due to AMD through injection into the eye.
Use context
Routes, doses, and cycle patterns
Empaveli uses a subcutaneous infusion pump or its labeled injector; Syfovre is an intravitreal injection administered by a qualified physician.
Human studies and product labels
Empaveli label, adult PNH
- Purpose
- Paroxysmal nocturnal hemoglobinuria in adults
- Context
- Label-reported prescription use
- Route
- Subcutaneous infusion or labeled injector
- Amount
- 1,080 mg
- Frequency
- Twice weekly
The label provides separate directions for switching from a C5 inhibitor and adjusting frequency when lactate dehydrogenase is elevated.
Empaveli label, adult kidney disease
- Purpose
- C3G or primary IC-MPGN in adults
- Context
- Label-reported prescription use
- Route
- Subcutaneous infusion or labeled injector
- Amount
- 1,080 mg
- Frequency
- Twice weekly
Vaccination, infection precautions, and the Empaveli REMS apply.
Empaveli label, ages 12 to 17 with kidney disease
- Purpose
- C3G or primary IC-MPGN in pediatric patients
- Context
- Label-reported weight-based dosing
- Route
- Subcutaneous
- Amount
- At 50 kg or more, 1,080 mg for both initial doses and maintenance. From 35 kg to under 50 kg, the first dose is 648 mg and later doses are 810 mg. Below 35 kg, the first two doses are 540 mg and later doses are 648 mg.
- Frequency
- Twice weekly
These pediatric weight bands apply to the kidney indication; the PNH label covers adults.
Syfovre U.S. label
- Purpose
- Geographic atrophy secondary to AMD
- Context
- Label-reported prescription use
- Route
- Intravitreal injection into each affected eye
- Amount
- 15 mg in 0.1 mL
- Frequency
- Once every 25 to 60 days
A qualified physician administers the product; ocular monitoring is part of care.
PEGASUS PNH trial
- Purpose
- Hemoglobin change in patients with residual anemia on eculizumab
- Context
- Randomized active-comparator study
- Route
- Subcutaneous pegcetacoplan
- Amount
- 1,080 mg versus continued eculizumab
- Frequency
- Twice weekly after a 4-week run-in with both medicines
- Duration
- 16-week randomized comparison
The adjusted difference in hemoglobin change favored pegcetacoplan by 3.84 g/dL.
VALIANT kidney trial
- Purpose
- Change in urine protein-to-creatinine ratio
- Context
- Randomized placebo-controlled study
- Route
- Subcutaneous infusion
- Amount
- Adults received 1,080 mg; adolescent doses varied by weight.
- Frequency
- Twice weekly
- Duration
- 26-week placebo-controlled comparison
The trial reported a 68.1% relative reduction in urine protein versus placebo.
OAKS and DERBY eye trials
- Purpose
- Growth of geographic atrophy lesions
- Context
- Randomized sham-controlled studies
- Route
- Intravitreal injection
- Amount
- 15 mg in 0.1 mL versus sham
- Frequency
- Monthly or every other month
- Duration
- 24 months of follow-up
OAKS met its 12-month lesion endpoint; DERBY did not. At 24 months both reported less lesion growth, with no difference in key visual-function endpoints.
Research
Research evidence
The systemic and ocular programs studied different conditions and outcomes. PEGASUS measured hemoglobin in a specific PNH population; VALIANT measured urine protein in C3G and primary IC-MPGN. OAKS and DERBY measured retinal atrophy growth and visual function in AMD.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| PEGASUS | Adults with PNH and hemoglobin below 10.5 g/dL despite stable eculizumab | Randomized, open-label, active-comparator trial | Subcutaneous pegcetacoplan versus continued eculizumab | Hemoglobin change at week 16 favored pegcetacoplan by an adjusted 3.84 g/dL. | The comparison included a selected population with residual anemia and was open-label. | Strong |
| VALIANT | 124 randomized adolescents and adults with C3G or primary IC-MPGN | Double-blind, placebo-controlled phase 3 trial | Subcutaneous pegcetacoplan versus placebo | At week 26, urine protein-to-creatinine ratio changed by -67.2% with pegcetacoplan and +2.9% with placebo, a relative reduction of 68.1%. | The separate change in estimated filtration rate was not formally tested in the reported hierarchical analysis. The label says safety and effectiveness in recurrent primary IC-MPGN after a kidney transplant have not been established. | Strong |
| OAKS and DERBY | People aged 60 and older with geographic atrophy secondary to AMD | Two double-masked, sham-controlled randomized phase 3 trials | Intravitreal pegcetacoplan monthly or every other month | Lesion growth was significantly reduced in OAKS at 12 months but not in DERBY; both trials showed reduced growth at 24 months. | Key secondary visual-function endpoints did not differ at 24 months. | Strong |
Cautions
Safety and unknowns
- Empaveli's boxed warning addresses serious infection with encapsulated bacteria. These infections can progress rapidly and can occur despite vaccination. Suspected serious infection requires immediate evaluation.
- Empaveli is contraindicated in people with hypersensitivity to pegcetacoplan or its ingredients. It must not be started during an unresolved serious infection caused by encapsulated bacteria.
- Empaveli's label calls for recommended vaccination at least 2 weeks before the first dose when possible. For urgent treatment in patients not up to date, it describes antibacterial prophylaxis and vaccination as soon as possible.
- After Empaveli is stopped in PNH, the label calls for monitoring for hemolysis for at least 8 weeks. Empaveli is available through a restricted REMS program.
- Empaveli may harm a fetus. Its label recommends pregnancy testing before treatment for females who can become pregnant, effective contraception during treatment and for 40 days after the last dose, and stopping breastfeeding during treatment and for 40 days after the last dose.
- Syfovre is contraindicated in people with an eye or surrounding-area infection, active inflammation inside the eye, or hypersensitivity to pegcetacoplan or its ingredients.
- Syfovre's label warns about endophthalmitis, retinal detachment, and retinal vasculitis or vascular occlusion that may cause severe vision loss. New eye pain, redness, or vision changes need prompt ophthalmic care. The label directs discontinuation if retinal vasculitis or vascular occlusion develops.
- Syfovre's label recommends effective contraception for females who can become pregnant during treatment and for 40 days after the last dose.
- In the eye trials summarized in the label, neovascular AMD occurred by month 24 in 12% of monthly-treated patients, 7% of every-other-month patients, and 3% of controls.
Product quality
Product identity and quality
Empaveli and Syfovre are separate sterile products with different concentrations and administration routes.
Product and route
Empaveli is subcutaneous, while Syfovre is administered into the eye by a qualified physician.
Indication and age
Empaveli's PNH indication is for adults; its kidney indication includes patients aged 12 and older with weight-based pediatric dosing.
Mechanism
How it is proposed to work
Pegcetacoplan binds C3 and C3b, reducing downstream activation of the complement system. The effects studied depend on the disease and the product's route.
In PNH, C3b contributes to destruction of blood cells outside the circulation, while later complement activity contributes to destruction within blood vessels.
In C3G and primary IC-MPGN, complement dysregulation is associated with C3 fragment deposition in the kidney's filtering units.
Details
Technical details
Sources
References
- 1.
DailyMed. Empaveli prescribing information
- 2.
DailyMed. Syfovre prescribing information
- 3.
PubMed. PEGASUS randomized trial in paroxysmal nocturnal hemoglobinuria
doi:10.1056/NEJMoa2029073 PMID:33730455 NCT03500549
- 4.
PubMed. VALIANT randomized trial in C3G and primary IC-MPGN
doi:10.1056/NEJMoa2501510 PMID:41337715 NCT05067127
- 5.
PubMed. OAKS and DERBY randomized trials in geographic atrophy
PMID:37865470