Introduction
Pegcetacoplan ophthalmic solution is a targeted C3 complement inhibitor approved for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). As the first FDA-approved pharmacotherapy for this vision-threatening condition, it represents a significant advancement in retinal therapeutics. Pegcetacoplan works by modulating the complement system, which plays a key role in the inflammatory processes driving GA progression.
Mechanism of Action
Pegcetacoplan is a cyclic peptide conjugated to a polyethylene glycol polymer that specifically binds to complement protein C3 and its activation fragment C3b. This binding inhibits the cleavage of C3 into C3a and C3b, thereby preventing downstream complement activation through all pathways (classical, lectin, and alternative). By inhibiting complement-mediated inflammation and cell lysis, pegcetacoplan reduces the progression of geographic atrophy lesions in the retina.
Indications
- Treatment of geographic atrophy secondary to age-related macular degeneration
Dosage and Administration
Recommended dosage: 15 mg (0.1 mL of 150 mg/mL solution) administered by intravitreal injection every 25 to 60 days Administration:- For ophthalmic intravitreal injection only
- Must be administered by a qualified physician
- The recommended treatment interval is every 25 to 60 days
- Administer using aseptic technique
- Monitor patients following injection for elevation in intraocular pressure
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment necessary
Pharmacokinetics
Absorption: Following intravitreal administration, pegcetacoplan achieves therapeutic concentrations in the vitreous humor and retina Distribution: Limited systemic exposure following ocular administration Metabolism: Undergoes peptide hydrolysis to smaller peptides and amino acids Elimination: Primarily eliminated via renal excretion of metabolites Half-life: Approximately 6-8 days in the vitreous humorContraindications
- Ocular or periocular infections
- Active intraocular inflammation
- Hypersensitivity to pegcetacoplan or any component of the formulation
Warnings and Precautions
Boxed Warning:- Endophthalmitis and retinal detachments may occur following intravitreal injections
- Exudative age-related macular degeneration has been reported following treatment
- Increased intraocular pressure may occur following injection
- Monitor for intraocular inflammation
- Patients may experience increased rates of exudative AMD conversion
- Use caution in patients with history of uveitis
- Proper aseptic injection technique must be maintained
Drug Interactions
- No formal drug interaction studies have been conducted
- Theoretical potential for interactions with other complement inhibitors
- No known interactions with systemic medications
Adverse Effects
Most common adverse reactions (≥5%):- Ocular discomfort (15%)
- Neovascular AMD (12%)
- Increased intraocular pressure (9%)
- Vitreous floaters (8%)
- Conjunctival hemorrhage (7%)
- Endophthalmitis (<1%)
- Retinal detachment (<1%)
- Intraocular inflammation (2%)
- Retinal vasculitis (rare)
Monitoring Parameters
Ophthalmic monitoring:- Visual acuity assessment at each visit
- Dilated retinal examination monthly
- Optical coherence tomography (OCT) monitoring
- Fluorescein angiography as needed
- Intraocular pressure measurement pre- and post-injection
- Signs and symptoms of endophthalmitis (eye pain, redness, photophobia, vision changes)
- Symptoms of retinal detachment (new or increased floaters, flashes of light, visual field defects)
- Monitoring for conversion to exudative AMD
Patient Education
- Report any eye pain, redness, sensitivity to light, or vision changes immediately
- Understand the risk of developing wet AMD and report any sudden vision changes
- Expect to see floaters after injection, but report if they increase significantly
- Maintain regular appointment schedule for injections and monitoring
- Understand that treatment aims to slow disease progression rather than improve vision
- Report any systemic symptoms that might suggest hypersensitivity reactions
References
1. FDA prescribing information: Syfovre™ (pegcetacoplan) injection 2. Liao DS, Grossi FV, El Mehdi D, et al. Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial. Ophthalmology. 2020;127(2):186-195. 3. Apellis Pharmaceuticals. Phase 3 DERBY and OAKS study data. 2022. 4. Jaffe GJ, Westby K, Csaky KG, et al. C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Ophthalmology. 2021;128(4):576-586. 5. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern® Guidelines. Age-Related Macular Degeneration. 2019.