Aflibercept

A medicine injected into the eye that blocks VEGF, a protein that drives the growth of blood vessels. It is used for several eye diseases, including, in the United States since 2023, retinopathy of prematurity. In the FIREFLEYE trial it did not meet the rule for matching laser treatment.

Drug
In this atlas

Overview

Technical summary

Drug, level substance. RxCUI 1232150 (RxNav name aflibercept, term type IN) read 2026-10-15. The Eylea label calls Eylea a vascular endothelial growth factor (VEGF) inhibitor. The one claim on this page is FIREFLEYE (a noninferiority trial of aflibercept against laser, whose result did not meet the criteria), with the label's listing of ROP given as context; it is an evaluated-for link, not a treats link. The ROP approval and the treats link are on the Eylea ROP page.

About this drug

Level: Substance
Mechanism: A vascular endothelial growth factor (VEGF) inhibitor (Eylea label).

Claims and evidence

Context Infants with retinopathy of prematurity needing treatment (FIREFLEYE trial)

Recipient: Newborn
Population: 118 infants were randomised: gestational age 32 weeks or less at birth or birth weight 1500 g or less, with ROP of specified severity (zone I stage 1+, 2+, 3 or 3+, or zone II stage 2+ or 3+) needing treatment, or with aggressive posterior ROP, in at least one eye. 113 were treated and 104 completed the study. They were enrolled between September 25, 2019, and August 28, 2020, at 64 hospital sites in 27 countries across Asia, Europe and South America.
Care setting: 64 hospital sites in 27 countries throughout Asia, Europe and South America
Geography: 27 countries across Asia, Europe and South America (the abstract names none)
Life stage: Infants with retinopathy of prematurity requiring treatment, with 24 weeks of follow-up
Gestational age: Not reported
Postnatal age: Not reported
Follow-up: The primary outcome was treatment success 24 weeks after starting treatment: no active ROP and no unfavourable structural outcomes, assessed by investigators; the need for rescue treatment counted as treatment failure.

Eligibility: 1 inclusion criterion; exclusion criteria not stated

Included: Gestational age 32 weeks or less at birth, or birth weight 1500 g or less, with ROP needing treatment or aggressive posterior ROP in at least one eye
Excluded: None stated

Effect Interventional Certainty not assessed

In FIREFLEYE, infants with retinopathy of prematurity needing treatment were randomised 2:1 to a 0.4-mg dose of intravitreal aflibercept (75 infants) or laser photocoagulation (43 infants randomised, 38 treated). Treatment success at 24 weeks was 85.5% with aflibercept and 82.1% with laser (between-group difference 3.4%; 1-sided 95% credible interval, -8.0% to infinity). Aflibercept was to be judged noninferior if the lower limit of that interval was above -5%; the authors report that it did not meet the criteria for noninferiority. Rescue treatment was needed in 4.8% of eyes in the aflibercept group and 11.1% in the laser group. Serious adverse events were 13.3% (ocular) and 24.0% (systemic) with aflibercept and 7.9% and 36.8% with laser. Three deaths, 4 to 9 weeks after aflibercept treatment, were considered unrelated to aflibercept by the investigators. The authors say further data are needed for more definitive conclusions. Separately, the US Eylea label lists retinopathy of prematurity among its five indications.
Applies to Newborn
- 118 infants were randomised: gestational age 32 weeks or less at birth or birth weight 1500 g or less, with ROP of specified severity (zone I stage 1+, 2+, 3 or 3+, or zone II stage 2+ or 3+) needing treatment, or with aggressive posterior ROP, in at least one eye. 113 were treated and 104 completed the study. They were enrolled between September 25, 2019, and August 28, 2020, at 64 hospital sites in 27 countries across Asia, Europe and South America.
- 64 hospital sites in 27 countries throughout Asia, Europe and South America
- 27 countries across Asia, Europe and South America (the abstract names none)
- Infants with retinopathy of prematurity requiring treatment, with 24 weeks of follow-up
- Gestational age Not reported
- Postnatal age Not reported
Follow-up The primary outcome was treatment success 24 weeks after starting treatment: no active ROP and no unfavourable structural outcomes, assessed by investigators; the need for rescue treatment counted as treatment failure.
Certainty method
Not assessed

Limitations
Only the abstract was read. The abstract does not state whether the trial was masked; its primary outcome was assessed by investigators at 24 weeks. Noninferiority was not shown, so this record does not say aflibercept works as well as laser. The label lists the indication; the abstract and the label are separate sources, and the label wording does not rest on this trial in anything read here.

Last checked
2026-10-15

Next evidence check due
Not scheduled
Sources and citations (3)
1. Supports Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial
  
  Publication · JAMA · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2022-07-26 · DOI: 10.1001/jama.2022.10564 · PMID: 35881122 · PMCID: PMC9327573
  
  Locator
  Abstract, RESULTS sentences 3 to 6 and CONCLUSIONS AND RELEVANCE
  
  How it applies
  Treatment success, rescue treatment, adverse events, deaths and the authors' conclusion.
  
  Retrieved
  2026-10-15T13:49:23Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  cc9f28da5292d3e890c048e260579f8628ef364cf742dafd6d12c8ee06b5274a
  
  Reuse basis
  PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.
2. Background Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial
  
  Publication · JAMA · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2022-07-26 · DOI: 10.1001/jama.2022.10564 · PMID: 35881122 · PMCID: PMC9327573
  
  Locator
  Abstract, OBJECTIVE, DESIGN, INTERVENTIONS and MAIN OUTCOMES
  
  How it applies
  Population, groups, outcome and noninferiority rule.
  
  Retrieved
  2026-10-15T13:49:23Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  cc9f28da5292d3e890c048e260579f8628ef364cf742dafd6d12c8ee06b5274a
  
  Reuse basis
  PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.
3. Background Eylea prescribing information for BLA125387: openFDA drug label record
  
  Regulator · U.S. Food and Drug Administration (openFDA) · Edition The openFDA drug label endpoint, fetched on 2026-10-15. The wording is the dataset's copy of the label as of the date fetched, not the current DailyMed label.
  
  Locator
  results[0].indications_and_usage[0]
  
  How it applies
  Label lists ROP among five indications; openFDA label CC0.
  
  Retrieved
  2026-10-15T13:51:07Z
  
  Source effective date
  Not reported
  
  Source state
  Current
  
  Snapshot hash
  1ca62da9d61b815e545b5bbf2ee65ea6f4a2c8d605f1b4793097c9bb8cea7890
  
  Reuse basis
  openFDA data is public domain under a Creative Commons CC0 1.0 Universal dedication unless noted (https://open.fda.gov/terms/, https://open.fda.gov/license/; the licence page was fetched as mn-openfda-license.html, sha256 7fda0041a24f8d7139a1781d4462ae39643a2ee6f3b0f079946c989a8e1982d2). The raw record is committed at research/snapshots/mn-openfda-label-BLA125387.json. Short quotations only.

Clinical links

Each link reports what one cited claim says about one population. "Evaluated for" means studied, not shown to work. These links do not show that anything is effective or right for you.

Claim, not a settled fact FIREFLEYE: aflibercept compared with laser in infants with ROP needing treatment: Retinopathy of prematurity (Evaluated for)
Applies to Newborn
- 118 infants were randomised: gestational age 32 weeks or less at birth or birth weight 1500 g or less, with ROP of specified severity (zone I stage 1+, 2+, 3 or 3+, or zone II stage 2+ or 3+) needing treatment, or with aggressive posterior ROP, in at least one eye. 113 were treated and 104 completed the study. They were enrolled between September 25, 2019, and August 28, 2020, at 64 hospital sites in 27 countries across Asia, Europe and South America.
- 64 hospital sites in 27 countries throughout Asia, Europe and South America
- 27 countries across Asia, Europe and South America (the abstract names none)
- Infants with retinopathy of prematurity requiring treatment, with 24 weeks of follow-up
- Gestational age Not reported
- Postnatal age Not reported
Follow-up The primary outcome was treatment success 24 weeks after starting treatment: no active ROP and no unfavourable structural outcomes, assessed by investigators; the need for rescue treatment counted as treatment failure.
In FIREFLEYE, infants with retinopathy of prematurity needing treatment were randomised 2:1 to a 0.4-mg dose of intravitreal aflibercept (75 infants) or laser photocoagulation (43 infants randomised, 38 treated). Treatment success at 24 weeks was 85.5% with aflibercept and 82.1% with laser (between-group difference 3.4%; 1-sided 95% credible interval, -8.0% to infinity). Aflibercept was to be judged noninferior if the lower limit of that interval was above -5%; the authors report that it did not meet the criteria for noninferiority. Rescue treatment was needed in 4.8% of eyes in the aflibercept group and 11.1% in the laser group. Serious adverse events were 13.3% (ocular) and 24.0% (systemic) with aflibercept and 7.9% and 36.8% with laser. Three deaths, 4 to 9 weeks after aflibercept treatment, were considered unrelated to aflibercept by the investigators. The authors say further data are needed for more definitive conclusions. Separately, the US Eylea label lists retinopathy of prematurity among its five indications.
Limitations. Only the abstract was read. The abstract does not state whether the trial was masked; its primary outcome was assessed by investigators at 24 weeks. Noninferiority was not shown, so this record does not say aflibercept works as well as laser. The label lists the indication; the abstract and the label are separate sources, and the label wording does not rest on this trial in anything read here.

Record details

Record id: maternal:aflibercept
Content hash: a2d59e15bba670d1f3081c626c25f26b92a0a85f273063b41b37d7ea7af2277c