Avacincaptad pegol



Avacincaptad pegol is an RNA aptamer inhibiting the complement C5 indicated for the treatment of geographic atrophy secondary to age-related macular degeneration.

Brand Names
Generic Name
Avacincaptad pegol
DrugBank Accession Number

Avacincaptad pegol is an RNA aptamer covalently bound to a branched polyethylene glycol (PEG) molecule. It was developed to treat an advanced form of age-related macular degeneration (AMD) called geographic atrophy (GA).4 AMD is the leading cause of vision loss in developed countries for people over 50 years old, with a global estimate of 170 million individuals affected. AMD eventually progresses to bilateral and irreversible loss of vision, whether or not the patients have the non-neovascular (dry) or the neovascular (wet) form of AMD.2 Although anti-VEGF therapy is available for the neovascular form of AMD, no treatment was approved for GA.2

Avacincaptag pegol was approved by the FDA on August 4, 2023, under the brand name IZERVAY for the treatment of GA secondary to AMD. This approval is based on the positive results obtained from 2 phase 3 clinical trials GATHER1 and GATHER2.5

Approved, Investigational
Biologic Classification
Nucleic Acid Based Therapies
  • Avacincaptad pegol



Avacincaptad pegol is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).4

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofDry macular degeneration••••••••••••••••••••
Contraindications & Blackbox Warnings
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Complement C5 is cleaved into C5a and C5b, and it is the final step of the complement cascade where a membrane attacking complex (MAC) is formed to cause cell death.1,2 This is thought to be a major contributor to the pathophysiology of age-related macular degeneration (AMD), as immunohistochemical studies demonstrated complement deposition in postmortem eyes of patients diagnosed with AMD.2 Additionally, 50% of patients with AMD were also found to have mutations in genes regulating the complement cascade, further implicating this pathway in deteriorating retinal health.2 By inhibiting the cleavage of complement C5, avacincaptad pegol can dampen the inflammatory processes, thus slowing down retinal cell injuries and degeneration.2

Increased geographic atrophy area (GA) growth is reflective of the loss of photoreceptors and AMD disease progression, and reductions in the rate of geographic atrophy growth were observed from baseline through the first year of treatment across avacincaptad pegol treatment groups in studies GATHER1 and GATHER2.4 Specifically, a GA growth rate reduction of 29% was observed in patients receiving avacincaptad pegol monthly or 20% in patients receiving the treatment every other month.3

Mechanism of action

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.4

AComplement C5

Following a single dose of avacincaptad pegol, maximum avacincaptad pegol plasma concentrations (Cmax) are estimated to occur approximately 7 days post-dose and mean (CV%) free avacincaptad pegol plasma Cmax is estimated to be 68.4 ng/mL (57.8%) in neovascular AMD (nAMD) patients. The AUC0-28 days following a single 2 mg dose is 1064 day∙ng/mL. Based on a population pharmacokinetic analysis of patients with nAMD, the predicted steady-state avacincaptad pegol Cmax is 83.9 ng/mL after monthly intravitreal administration of avacincaptad pegol 2 mg.4

In humans, avacincaptad pegol plasma concentrations are predicted to be approximately 7,000-fold lower than vitreal concentrations.4

Volume of distribution

Limited information is available on the volume of distribution of avacincaptad pegol

Protein binding

Limited information is available on the protein binding of avacincaptad pegol


The metabolism of avacincaptad pegol has not been fully characterized. Avacincaptad pegol is expected to be catabolized by endonucleases and exonucleases to oligonucleotides of shorter lengths.4

Route of elimination

The elimination of avacincaptad pegol has not been fully characterized. Avacincaptad pegol is expected to be catabolized by endonucleases and exonucleases to oligonucleotides of shorter lengths which may be excreted renally, in a similar manner to the elimination of endogenous RNA.4


The estimated apparent systemic half-life of avacincaptad pegol is approximately 12 days.4


Limited information is available on the clearance of avacincaptad pegol

Adverse Effects
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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.4

The administration of avacincaptad pegol to pregnant rats and rabbits throughout the period of organogenesis resulted in no evidence of adverse effects on the fetus or pregnant female at intravenous (IV) doses 5.1 times and 3.2 times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 2 mg once monthly, respectively.4

No studies have been conducted on the carcinogenic potential of avacincaptad pegol.4

Avacincaptad pegol was negative in in vitro (bacterial reverse mutation assay, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.4

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.


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Product Ingredients
IngredientUNIICASInChI Key
Avacincaptad pegol sodiumK86ENL12I51491144-00-3Not applicable
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IzervayInjection20 mg/1mLIntravitrealAstellas Pharma US, Inc.2023-08-19Not applicableUS flag


Drug Categories
Not classified
Affected organisms
Not Available

Chemical Identifiers

CAS number


General References
  1. Niculescu T, Weerth S, Niculescu F, Cudrici C, Rus V, Raine CS, Shin ML, Rus H: Effects of complement C5 on apoptosis in experimental autoimmune encephalomyelitis. J Immunol. 2004 May 1;172(9):5702-6. doi: 10.4049/jimmunol.172.9.5702. [Article]
  2. Jaffe GJ, Westby K, Csaky KG, Mones J, Pearlman JA, Patel SS, Joondeph BC, Randolph J, Masonson H, Rezaei KA: C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Ophthalmology. 2021 Apr;128(4):576-586. doi: 10.1016/j.ophtha.2020.08.027. Epub 2020 Sep 1. [Article]
  3. Cabral de Guimaraes TA, Daich Varela M, Georgiou M, Michaelides M: Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions. Br J Ophthalmol. 2022 Mar;106(3):297-304. doi: 10.1136/bjophthalmol-2020-318452. Epub 2021 Mar 19. [Article]
  4. FDA Approved Drug Products: IZERVAY™ (avacincaptad pegol) intravitreal solution [Link]
  5. Iveric Bio Receives U.S. FDA Approval for IZERVAY™ (avacincaptad pegol intravitreal solution), a New Treatment for Geographic Atrophy [Link]

Clinical Trials

Clinical Trials
3Active Not RecruitingTreatmentAge - Related Macular Degeneration (AMD) / Dry Macular Degeneration1
3CompletedTreatmentDry Macular Degeneration / Macular Degeneration1
2Active Not RecruitingTreatmentStargardt's Macular Dystrophy1
2CompletedTreatmentNeovascular Age-Related Macular Degeneration (nAMD)1
2TerminatedTreatmentMacular Degeneration1


Not Available
Not Available
Dosage Forms
InjectionIntravitreal20 mg/1mL
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US11491176No2014-07-112034-07-11US flag
US11273171No2014-07-112034-07-11US flag
US10947544No2021-03-162025-02-14US flag
US9617546No2017-04-112025-02-14US flag
US8236773No2012-08-072026-11-11US flag
US7803931No2010-09-282025-02-14US flag
US7538211No2009-05-262025-02-14US flag
US7579456No2009-08-252025-02-14US flag


Experimental Properties
Not Available


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Pharmacological action
General Function
Receptor binding
Specific Function
Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C...
Gene Name
Uniprot ID
Uniprot Name
Complement C5
Molecular Weight
188303.705 Da
  1. FDA Approved Drug Products: IZERVAY™ (avacincaptad pegol) intravitreal solution [Link]

Drug created at May 20, 2019 14:55 / Updated at November 01, 2023 05:14