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Complement C5 Inhibitor — Geographic Atrophy (AMD) Pregnancy: No data — not applicable (disease of older adults)

Avacincaptad Pegol Intravitreal Injection

Brand names: Izervay

Adult dose

Dose: 2 mg (0.1 mL) intravitreal injection
Route: Intravitreal injection (administered by specialist)
Frequency: Every month
Max: 2 mg per injection
FDA approved August 2023 — second treatment approved for geographic atrophy; reduces GA lesion growth by ~35% vs sham at 12 months (GATHER1 and GATHER2 trials); monthly injections only; MHRA review ongoing; complement C5 inhibitor (vs C3 for pegcetacoplan)

Paediatric dose

Route: N/A
Frequency: N/A
Max: Not indicated in children
No paediatric indication — GA is a disease of older adults

Dose adjustments

Renal

No adjustment required (local delivery)

Hepatic

No adjustment required

Clinical pearls

  • FDA approval August 2023: second approval for geographic atrophy (first was pegcetacoplan in February 2023) — two complementary treatments now exist with different complement targets; choice will depend on patient profile, dosing frequency preference, and lesion characteristics
  • C5 vs C3 inhibition: avacincaptad pegol targets C5 (terminal complement pathway only) — blocks formation of membrane attack complex (MAC); pegcetacoplan targets C3 (central complement cascade — both classical and alternative pathways); C3 inhibition is broader but also blocks opsonisation and immune surveillance more extensively
  • GATHER1 and GATHER2 trials: GATHER1 (Ophthalmology 2021) and GATHER2 (NEJM 2023) — avacincaptad pegol 2 mg significantly reduced GA growth rate by 33–35% vs sham at 12 months; consistent results across both trials; strongest GA growth rate reduction of both approved treatments
  • Exudative conversion risk: monthly injections associated with ~6–8% annual risk of wet AMD conversion vs ~1–2% sham — higher than pegcetacoplan; all GA patients on complement inhibitors require monthly OCT monitoring to detect and treat wet conversion promptly with anti-VEGF
  • Clinical context for both GA treatments: neither drug significantly improves visual acuity — they slow GA progression (area of death), not reverse it; patient counselling must emphasise that treatment prevents future vision loss rather than improving current vision; long-term benefit may be demonstrated in extension studies

Contraindications

  • Ocular or periocular infection
  • Active intraocular inflammation
  • Hypersensitivity to avacincaptad pegol or polyethylene glycol

Side effects

  • Exudative (wet) AMD conversion (clinically significant risk — ~6–8% per year)
  • Injection site reactions
  • Conjunctival haemorrhage
  • Eye discomfort
  • Floaters
  • Endophthalmitis (as with all intravitreal injections)

Interactions

  • No significant drug interactions — local delivery

Monitoring

  • OCT imaging monthly (exudative conversion monitoring — essential)
  • GA lesion area by fundus autofluorescence
  • Visual acuity (BCVA)
  • IOP post-injection
  • Intraocular inflammation signs

Reference: BNFc; BNF 90; FDA Approval Izervay August 2023; Khanani et al. Ophthalmology 2021 (GATHER1); Guymer et al. NEJM 2023 (GATHER2); RCOphth Position Statement on GA. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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