Pegcetacoplan

Pegcetacoplan binds to complement protein C3 and its activation fragment C3b with high affinity thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation

• SYFOVRE is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

• Ocular or Periocular Infections ( 4.1 ) Active Intraocular Inflammation ( 4.2 ) Hypersensitivity ( 4.3 ) 4.1 Ocular or Periocular Infections SYFOVRE is contraindicated in patients with ocular or periocular infections [see Warnings and Precautions (5.1) ] . 4.2 Active Intraocular Inflammation SYFOVRE is contraindicated in patients with active intraocular inflammation.contraindicated

The recommended dose for SYFOVRE is 15 mg (0.1 mL of 150 mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days. ( 2.2 ) 2.1 General Dosing Information SYFOVRE must be administered by a qualified physician. 2.2 Recommended Dosage The recommended dose for SYFOVRE is 15 mg (0.1 mL of 150 mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days. 2.3 Preparation for Administration Store SYFOVRE in the refrigerator between 2°C to 8°C (36°F to 46°F); Keep the vial in the original carton to protect from light. SYFOVRE is available packaged as follows: Vial Only Vial Kit with Injection Components (filter needle, syringe, injection needle) Remove the carton from the refrigerator. Keep the vial in the original carton at room temperature 20°C to 25°C (68°F to 77°F), for at least 15 minutes prior to injection, but no longer than 8 hours. Fill the syringe immediately prior to the injection. Do not shake the vial. The vial is for use in a single eye. Inspect the solution. It is a clear, colorless to light yellow aqueous solution.

Endophthalmitis and Retinal Detachments ( 5.1 ) Retinal Vasculitis and/or Retinal Vascular Occlusion ( 5.2 ) Neovascular AMD ( 5.3 ) Intraocular inflammation ( 5.4 ) Increased Intraocular Pressure ( 5.5 ) 5.1 Endophthalmitis and Retinal Detachments Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1) ] . Proper aseptic injection technique must always be used when administering SYFOVRE in order to minimize the risk of endophthalmitis [see Dosage and Administration (2.4) ] . Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. 5.2 Retinal Vasculitis and/or Retinal Vascular Occlusion Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE [see Adverse Reactions (6.2) ] . Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay. 5.3 Neovascular AMD In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD.

The following clinically significant adverse reactions are described elsewhere in the labeling: Ocular and periocular infections [see Contraindications (4.1) ] Active intraocular inflammation [see Contraindications (4.2) ] Hypersensitivity [see Contraindications (4.3) ] Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1) ] Retinal Vasculitis and/or Retinal Vascular Occlusion [see Warnings and Precautions (5.2) ] Neovascular AMD [see Warnings and Precautions (5.3) ] Intraocular inflammation [see Warnings and Precautions (5.4) ] Increased intraocular pressure [see Warnings and Precautions (5.5) ] Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, and conjunctival hemorrhage. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apellis Pharmaceuticals, Inc. at 1-833-866-3346 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 839 patients with GA in two Phase 3 studies (OAKS and DERBY) were treated with intravitreal SYFOVRE, 15 mg (0.1 mL of 150 mg/mL solution). Four hundred nineteen (419) of these patients were treated in the affected eye monthly and 420 were treated in the affected eye every other month. Four hundred seventeen (417) patients were assigned to sham.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of SYFOVRE administration in pregnant women to inform a drug-associated risk. The use of SYFOVRE may be considered following an assessment of the risks and benefits. Systemic exposure of SYFOVRE following ocular administration is low [see Clinical Pharmacology (12.3) ] . Subcutaneous administration of pegcetacoplan to pregnant monkeys from the mid gestation period through birth resulted in increased incidences of abortions and stillbirths at systemic exposures 1040-fold higher than that observed in humans at the maximum recommended human ophthalmic dose (MRHOD) of SYFOVRE (based on the area under the curve (AUC) systemically measured levels). No adverse maternal or fetal effects were observed in monkeys at systemic exposures approximately 470-fold higher than that observed in humans at the MRHOD (see Data ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In embryofetal development studies, subcutaneous administration of pegcetacoplan to pregnant cynomolgus monkeys from the mid gestation period through birth produced increased incidences of abortions and stillbirths at doses of 28 mg/kg/day [approximately 1040-fold higher than the MRHOD based on exposure (AUC)].

Metabolism

SYFOVRE is administered directly into the vitreous to exert local effects in the eye. Following repeat intravitreal administration of pegcetacoplan at a dose of 15 mg, geometric mean (%CV) serum C max value at steady state was 2.2 μg/mL (28.7%) and 1.5 μg/mL (58.1%) for GA patients dosed monthly and every other month, respectively.

• May 14, 2021NDANDA215014Apellis Pharms
• Feb 17, 2023NDANDA217171Apellis Pharms

1. 1Fatigue1549.2%
2. 2Visual Impairment1358.0%
3. 3Off Label Use1297.7%
4. 4Haemoglobin Decreased1207.2%
5. 5Vitreous Floaters1106.6%
6. 6Haemolysis1076.4%
7. 7Breakthrough Haemolysis875.2%
8. 8Headache814.8%
9. 9Uveitis754.5%
10. 10Vitritis704.2%
11. 11Product Dose Omission Issue653.9%
12. 12Choroidal Neovascularisation643.8%
13. 13Drug Ineffective643.8%
14. 14Eye Inflammation633.8%
15. 15Vision Blurred613.6%

The 10 most recently updated of 33 ClinicalTrials.gov registrations naming Pegcetacoplan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Pegcetacoplan in Combination With Modified FOLFIRINOX for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma
  Recruiting · Phase 1 · Phase 2 · Interventional · 35 enrolled · Roswell Park Cancer Institute
  NCT07214298updated 2026-06-08
• Pegcetacoplan Long Term Safety and Efficacy Extension Study
  Completed · Phase 3 · Interventional · 137 enrolled · Apellis Pharmaceuticals, Inc.
  NCT03531255updated 2026-06-05
• A Phase 2, Randomized, Placebo Controlled, Multicenter, Masked Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Multidose APL 3007 in Combination With Syfovre/Pegcetacoplan (APL-2) in Patients Diagnosed With Geographic Atrophy Secondary to Age Related Macular Degeneratio
  Recruiting · Phase 2 · Interventional · 240 enrolled · Apellis Pharmaceuticals, Inc.
  NCT07215390updated 2026-06-04
• A Prospective, Multicenter, Open-Label, Observational Phase 4 Study to Evaluate Real-World Safety, Tolerability, and Treatment Patterns of Pegcetacoplan (Syfovre) in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration
  Active not recruiting · Observational · 300 enrolled · Apellis Pharmaceuticals, Inc.
  NCT06161584updated 2026-06-01
• Lesion-tailored, Fundus-controlled Perimetry in Geographic Atrophy (GA).
  Not yet recruiting · Observational · 50 enrolled · University of Utah
  NCT07582042updated 2026-05-18
• A Study to Test Whether BI 771716 Helps People With an Advanced Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy
  Active not recruiting · Phase 2 · Interventional · 202 enrolled · Boehringer Ingelheim
  NCT06722157updated 2026-05-14
• A Study to Investigate Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), and Immunogenicity of RO7669330 in Participants With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)
  Active not recruiting · Phase 1 · Interventional · 27 enrolled · Hoffmann-La Roche
  NCT06961370updated 2026-05-07
• Safely Quenching Complement in Stroke Survivors
  Not yet recruiting · Phase 1 · Interventional · 20 enrolled · Columbia University
  NCT07495722updated 2026-04-29
• Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN
  Completed · Phase 2 · Interventional · 13 enrolled · Apellis Pharmaceuticals, Inc.
  NCT04572854updated 2026-04-21
• An Open-Label, Nonrandomized, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan in Participants With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
  Active not recruiting · Phase 3 · Interventional · 100 enrolled · Apellis Pharmaceuticals, Inc.
  NCT05809531updated 2026-04-02

Frequently asked questions

How does Pegcetacoplan work?

Pegcetacoplan binds to complement protein C3 and its activation fragment C3b with high affinity thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation

What is Pegcetacoplan used for?

According to FDA labeling, Pegcetacoplan carries indications including: SYFOVRE is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pegcetacoplan?

Pegcetacoplan is classified as Complement inhibitors, Other ophthalmologicals, Complement Inhibitor, Complement Inhibitors.

What are the brand names for Pegcetacoplan?

Pegcetacoplan is marketed under brand names including Empaveli, Syfovre.

What are the contraindications for Pegcetacoplan?

Pegcetacoplan labeling lists contraindications including: Ocular or Periocular Infections ( 4.1 ) Active Intraocular Inflammation ( 4.2 ) Hypersensitivity ( 4.3 ) 4.1 Ocular or Periocular Infections SYFOVRE is contraindicated in patients with ocular or periocular infections [see Warnings and Precautions (5.1) ] . 4.2 Active Intraocular Inflammation SYFOVRE is contraindicated in patients with active intraocular inflammation.. Always consult the full prescribing information and a clinician.