Avacincaptad Pegol

Avacincaptad pegol is an RNA aptamer, a PEGylated oligonucleotide that binds to and inhibits complement protein C5. By inhibiting C5, avacincaptad pegol may prevent its cleavage to C5a and C5b thus decreasing membrane attack complex (MAC) formation.

• IZERVAY ® is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). IZERVAY is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) ( 1 ).

• • Ocular or periocular infections ( 4.1 ). • Active intraocular inflammation ( 4.2 ).contraindicated

The recommended dosage for IZERVAY is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each affected eye once monthly (approximately 28 ± 7 days) ( 2.2 ). 2.1 General Dosing Information IZERVAY must be administered by a qualified physician. 2.2 Recommended Dosage The recommended dosage for IZERVAY is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each affected eye once monthly (approximately every 28 ± 7 days). 2.3 Preparation for Administration Important information you should know before you begin: • Read all the instructions carefully before using IZERVAY. • The IZERVAY kit includes a glass vial, filter needle, and an empty syringe. The glass vial, filter needle, and empty syringe are for single use only. • Store IZERVAY in the refrigerator at temperatures between 2ºC to 8ºC (36ºF to 46ºF). Do not freeze. Do not shake. • Prior to use, allow IZERVAY to reach room temperature, 20⁰C to 25⁰C (68⁰F to 77⁰F). The IZERVAY vial may be kept at room temperature for up to 24 hours. Keep the vial in the original carton to protect from light. • Use aseptic technique to carry out the preparation of the intravitreal injection. • Each vial should only be used for the treatment of a single eye. Step 1: Gather Supplies Gather the following supplies ( see Figure A ): a. One IZERVAY vial (included) b. One sterile 5-micron filter needle 18-gauge x 1½ inch (included) c. One sterile 1 mL Luer lock syringe with a 0.1 mL dose mark (included) d.

• Endophthalmitis and Retinal Detachments ( 5.1 ). • Neovascular AMD ( 5.2 ) • Increase in Intraocular Pressure (IOP) ( 5.3 ). 5.1 Endophthalmitis and Retinal Detachments Intravitreal injections may be associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1) ] . Proper aseptic injection techniques must always be used when administering IZERVAY 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, to permit prompt and appropriate management [see Patient Counseling Information (17) ] . 5.2 Neovascular AMD In the GATHER1 and GATHER2 clinical trials, use of IZERVAY was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (7% when administered monthly and 4% in the sham group) by Month 12. Over 24 months, the rate of neovascular (wet) AMD or choroidal neovascularization in the GATHER2 trial was 12% in the IZERVAY group and 9% in the sham group. Patients receiving IZERVAY should be monitored for signs of neovascular AMD. 5.3 Increase in Intraocular Pressure Transient increases in intraocular pressure (IOP) have been observed after an intravitreal injection, including with IZERVAY [see Adverse Reactions (6.1) ] . Perfusion of the optic nerve head should be monitored following the injection and managed as needed [see Dosage and Administration (2.4) ] .

The following potentially serious adverse reactions are described elsewhere in the labeling: • Ocular and periocular infections [see Contraindications (4.1) ] • Active intraocular inflammation [see Contraindications (4.2) ] • Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1) ] • Neovascular AMD [see Warnings and Precautions (5.2) ] • Increase in intraocular pressure [see Warnings and Precautions (5.3) ] The most common adverse reactions (incidence ≥ 5%) were conjunctival hemorrhage, increased IOP, blurred vision, neovascular age-related macular degeneration, punctate keratitis, and eye pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 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. The safety of avacincaptad pegol was evaluated in 733 patients with AMD in two sham-controlled studies (GATHER1 and GATHER2). Of these patients, 292 were treated with intravitreal IZERVAY 2 mg (0.1 mL of 20 mg/mL solution) [see Clinical Studies (14) ] . Three hundred thirty-two (332) patients were assigned to sham. Adverse reactions reported in ≥2% of patients who received treatment with IZERVAY for up to 12 months pooled across the GATHER1 and GATHER2 studies are listed below in Table 1 .

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of IZERVAY administration in pregnant women. The use of IZERVAY may be considered following an assessment of the risks and benefits. Administration of avacincaptad pegol to pregnant rats and rabbits throughout the period of organogenesis resulted in no evidence of adverse effects to the fetus or pregnant female at intravenous (IV) doses 5.5 times and 3.4 times the human exposure, respectively, based on Area Under the Curve (AUC), following a single 2 mg intravitreal (IVT) dose (see Data ) . In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15%-20%, respectively. Data Animal Data An embryo fetal developmental toxicity study was conducted with pregnant rats. Pregnant rats received daily IV injections of avacincaptad pegol from day 6 to day 17 of gestation at 0.1, 0.4, 1.2 mg/kg/day. No maternal or embryofetal adverse effects were observed at any dose evaluated. An increase in the incidence of a non-adverse skeletal variation, described as short thoracolumbar (ossification site without distal cartilage) supernumerary ribs, was observed at all doses evaluated. The clinical relevance of this finding is unknown.

Metabolism

Absorption/Distribution Following monthly dosing of avacincaptad pegol, at steady‑state maximum avacincaptad pegol plasma concentrations (C max ) are estimated to occur approximately 3 days post-dose and geometric mean (GeoCV%) free avacincaptad pegol plasma C max is estimated to be 347 ng/mL (59.0%) in GA secondary to AMD patients. The AUC 0-τ days following monthly dosing is 4726 day∙ng/mL, where tau is 28 days.

• Aug 4, 2023NDANDA217225Astellas

1. 1Intercepted Product Preparation Error238.8%
2. 2Needle Issue228.4%
3. 3No Adverse Event207.7%
4. 4Eye Pain197.3%
5. 5Vision Blurred197.3%
6. 6Off Label Use186.9%
7. 7Visual Impairment186.9%
8. 8Endophthalmitis166.1%
9. 9Syringe Issue155.7%
10. 10Intraocular Pressure Increased145.4%
11. 11Choroidal Neovascularisation135.0%
12. 12Eye Inflammation135.0%
13. 13Vitritis124.6%
14. 14Device Issue114.2%
15. 15Uveitis114.2%

The 10 most recently updated of 14 ClinicalTrials.gov registrations naming Avacincaptad Pegol as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Learn How Avacincaptad Pegol (Izervay™) is Used in Clinical Practice in People Who Have Geographic Atrophy
  Recruiting · Observational · 500 enrolled · Astellas Pharma Global Development, Inc.
  NCT06779773updated 2026-06-10
• Avacincaptad Pegol Open-Label Extension for Patients With Geographic Atrophy
  Completed · Phase 3 · Interventional · 278 enrolled · Astellas Pharma Global Development, Inc.
  NCT05536297updated 2026-05-18
• 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
• Zimura Compared to Sham in Patients With Autosomal Recessive Stargardt Disease (STGD1)
  Completed · Phase 2 · Interventional · 121 enrolled · Astellas Pharma Global Development, Inc.
  NCT03364153updated 2026-04-15
• A Study About the Safety of ASP3021 Eye Injections and if They Help People in Japan With Vision Loss From Age-related Macular Degeneration
  Recruiting · Phase 4 · Interventional · 20 enrolled · Astellas Pharma Inc
  NCT06970665updated 2026-02-27
• Study to Evaluate Efficacy and Safety of ONL1204 in Patients With GA Associated With AMD
  Recruiting · Phase 2 · Interventional · 324 enrolled · ONL Therapeutics
  NCT06659445updated 2025-12-05
• A Phase 3 Safety and Efficacy Study of Intravitreal Administration of Zimura (Complement C5 Inhibitor)
  Completed · Phase 3 · Interventional · 448 enrolled · IVERIC bio, Inc.
  NCT04435366updated 2025-10-21
• Zimura in Participants With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration
  Completed · Phase 2 · Phase 3 · Interventional · 286 enrolled · IVERIC bio, Inc.
  NCT02686658updated 2025-06-10
• ZIMURA in Combination With LUCENTIS in Patients With Neovascular Age Related Macular Degeneration (NVAMD)
  Completed · Phase 2 · Interventional · 64 enrolled · Ophthotech Corporation
  NCT03362190updated 2025-06-10
• A Study to Establish the Safety and Tolerability of Zimura™ (Anti-C5 Aptamer) in Combination With Anti-VEGF Therapy in Subjects With Idiopathic Polypoidal Choroidal Vasculopathy (IPCV)
  Completed · Phase 2 · Interventional · 4 enrolled · Ophthotech Corporation
  NCT02397954updated 2025-03-20

Frequently asked questions

How does Avacincaptad Pegol work?

Avacincaptad pegol is an RNA aptamer, a PEGylated oligonucleotide that binds to and inhibits complement protein C5. By inhibiting C5, avacincaptad pegol may prevent its cleavage to C5a and C5b thus decreasing membrane attack complex (MAC) formation.

What is Avacincaptad Pegol used for?

According to FDA labeling, Avacincaptad Pegol carries indications including: IZERVAY ® is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). IZERVAY is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Avacincaptad Pegol?

Avacincaptad Pegol is classified as Other ophthalmologicals, Complement Inhibitor, Complement Inhibitors.

What are the brand names for Avacincaptad Pegol?

Avacincaptad Pegol is marketed under brand names including Izervay.

What are the contraindications for Avacincaptad Pegol?

Avacincaptad Pegol labeling lists contraindications including: • Ocular or periocular infections ( 4.1 ). • Active intraocular inflammation ( 4.2 ).. Always consult the full prescribing information and a clinician.