Complement C3 Inhibitor — Geographic Atrophy (AMD) Pregnancy: No data in human pregnancy — GA is a disease of older adults; not applicable

Pegcetacoplan Intravitreal Injection

Brand names: Syfovre

Adult dose

Dose: 15 mg (0.1 mL) intravitreal injection

Route: Intravitreal injection (administered by specialist)

Frequency: Every month or every other month

Max: 15 mg per injection

FDA approved February 2023 — first-ever treatment approved for geographic atrophy (GA) secondary to AMD; monthly injections reduce GA growth rate by ~22%; every-other-month by ~16%; MHRA review ongoing; specialist retina service only

Paediatric dose

Route: N/A

Frequency: N/A

Max: Not indicated in children

GA is a disease of older adults; no paediatric indication

Dose adjustments

Renal

No adjustment required (local delivery, minimal systemic exposure)

Hepatic

No adjustment required

Clinical pearls

Historic milestone: pegcetacoplan (Syfovre) received FDA approval in February 2023 — the first drug EVER approved for geographic atrophy (GA) secondary to AMD; GA affects ~5 million people in the US and UK combined; previously completely untreatable beyond lifestyle modification and vitamin supplementation (AREDS2)
Mechanism — complement pathway: pegcetacoplan is a cyclic peptide that binds complement protein C3 and C3b — blocks the central hub of the complement cascade (both classical and alternative pathways); GA pathophysiology involves complement-mediated retinal pigment epithelium (RPE) cell death; targeting C3 provides broader complement inhibition than C5 (terminal pathway only)
OAKS and DERBY Phase 3 trials (NEJM 2023): primary endpoint — significant reduction in GA lesion growth rate vs sham at 12 months; monthly dosing reduced growth by 22%, alternate monthly by 16%; early-onset benefit at 6 months; longer-term vision benefit dependent on baseline lesion characteristics
Exudative (wet) AMD conversion risk: complement inhibition may paradoxically increase risk of choroidal neovascularisation (conversion to wet AMD) — pegcetacoplan-treated eyes showed ~2–6% annual conversion rate vs ~1–2% sham; requires concurrent monitoring with OCT; wet AMD conversion is treatable with anti-VEGF
MHRA approval status: regulatory review ongoing in UK (as of 2025); prescribers should check current approval status; compassionate use or clinical trial access may be available in specialist centres; NICE technology appraisal expected following MHRA decision

Contraindications

Ocular or periocular infection
Active intraocular inflammation
Known hypersensitivity to pegcetacoplan or PEG (polyethylene glycol)

Side effects

Exudative (wet) AMD conversion (~2–6% per year — higher than sham)
Injection site reactions
Retinal vasculitis (rare but serious)
Endophthalmitis (as with all intravitreal injections)
Floaters
Eye pain

Interactions

No significant drug interactions — local delivery with minimal systemic exposure

Monitoring

OCT imaging monthly for first 3–6 months then every 3 months (exudative conversion monitoring)
GA lesion area (fundus autofluorescence)
Visual acuity (BCVA)
IOP post-injection
Signs of intraocular inflammation

Reference: BNFc; BNF 90; FDA Approval Syfovre February 2023; Liao et al. NEJM 2023 (OAKS and DERBY); Wykoff et al. Ophthalmology 2023; RANZCO/RCOphth Position Statements on GA treatment. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways