Introduction
Syfovre (pegcetacoplan) is a first-in-class complement C3 inhibitor developed by Apellis Pharmaceuticals for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Approved by the FDA in February 2023, it represents a significant advancement in retinal therapeutics as the first pharmacologic treatment for this progressive, vision-threatening condition.
Mechanism of Action
Syfovre works by selectively inhibiting complement C3, a central protein in the complement cascade. The drug is a symmetric, pegylated peptide that binds to C3 and its activation fragment C3b, effectively regulating both the classical and alternative complement pathways. By modulating this key inflammatory pathway, Syfovre reduces the chronic inflammation and cell damage that contribute to the progression of geographic atrophy lesions.
Indications
Syfovre is indicated for the 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
- Dosing schedule: Every 25 to 60 days
- Administration: Must be administered by a qualified healthcare professional using aseptic technique
- Special populations: No dosage adjustment recommended for renal or hepatic impairment
- Preparation: Allow vial to reach room temperature before use; inspect for particulate matter and discoloration
Pharmacokinetics
- Absorption: Local ocular delivery with minimal systemic exposure
- Distribution: Primarily confined to the vitreous humor and retina
- Metabolism: Undergoes proteolytic degradation in ocular tissues
- Elimination: Systemic elimination half-life approximately 2-3 weeks
- Systemic exposure: Minimal plasma concentrations detected after intravitreal administration
Contraindications
- Ocular or periocular infections
- Active intraocular inflammation
- Hypersensitivity to pegcetacoplan or any component of the formulation
Warnings and Precautions
- Endophthalmitis and retinal detachments: May occur following any intravitreal injection procedure
- Intraocular inflammation: Can include uveitis, vitritis, and retinal vasculitis
- Increased intraocular pressure: Monitor following injection
- Neovascular AMD: Monitor for emergence of wet AMD; treatment may need to be adjusted
- Complement deficiency: Theoretical risk of increased susceptibility to infections
Drug Interactions
No formal drug interaction studies have been conducted. However, theoretical considerations include:
- Other complement inhibitors (potential additive effect)
- Immunosuppressive therapies (possible increased infection risk)
- No known interactions with commonly used ophthalmic medications
Adverse Effects
Most common adverse reactions (≥5%):- Ocular discomfort (15%)
- Neovascular AMD (12%)
- Vitreous floaters (9%)
- Conjunctival hemorrhage (8%)
- Increased intraocular pressure (7%)
- Choroidal neovascularization (6%)
- Endophthalmitis (<1%)
- Retinal detachment (<1%)
- Severe intraocular inflammation
- Ischemic optic neuropathy
Monitoring Parameters
- Visual acuity: At each visit
- Ophthalmic examination: Dilated fundus examination at baseline and regularly during treatment
- OCT imaging: Monthly initially, then as clinically indicated to monitor GA progression
- Intraocular pressure: 30 minutes post-injection and at follow-up visits
- Signs of infection: Monitor for symptoms of endophthalmitis
- Emergence of neovascular AMD: Regular monitoring for conversion to wet AMD
Patient Education
- Syfovre is administered by injection into the eye every 1-2 months
- You may experience temporary blurry vision, floaters, or eye redness after injection
- Report any eye pain, increased redness, sensitivity to light, or vision changes immediately
- Maintain regular appointment schedule as geographic atrophy requires ongoing treatment
- The treatment aims to slow disease progression rather than improve vision
- Discuss any other eye conditions or treatments with your ophthalmologist
- Inform all healthcare providers about your Syfovre treatment
References
1. FDA Prescribing Information: Syfovre (pegcetacoplan) injection. February 2023. 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 Clinical Trial. Ophthalmology. 2020;127(2):186-195. 3. Apellis Pharmaceuticals. OAKS and DERBY Phase 3 Study Results. Presented at AAO 2022. 4. Jaffe GJ, Westby K, Csaky KG, et al. C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial. Ophthalmology. 2021;128(4):576-586. 5. American Society of Retina Specialists. Guidelines for Intravitreal Injection Technique. 2022 Update.