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Intravitreal Aflibercept

Phase 3

Diabetic Macular Edema | Small molecule | Ophthalmology |Regeneron Pharmaceuticals, Inc.|Last Updated: Nov 14, 2025

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment881

FDA Designations

PRIORITY_REVIEW

Clinical trial landscape

Intravitreal Aflibercept · 8 trials · 7 indications

Phase 3 3Phase 2 4Phase 1 1
NCT01627249Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular EdemaDiabetic Macular Edema
COMPLETED660 Analytics
NCT02718326Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR)Nonproliferative Diabetic Retinopathy
COMPLETED402 Analytics
NCT00964795Open-label Extension Study of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) in Neovascular ("Wet") Age-related Macular Degeneration (AMD)Neovascular Age-related Macular Degeneration
COMPLETED323 Analytics
PHASE3COMPLETED
Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema
Diabetic Macular EdemaUnlock trial analytics
PHASE3COMPLETED
Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR)
Nonproliferative Diabetic RetinopathyUnlock trial analytics
PHASE3COMPLETED
Open-label Extension Study of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) in Neovascular ("Wet") Age-related Macular Degeneration (AMD)
Neovascular Age-related Macular DegenerationUnlock trial analytics

Study Endpoints

Primary Endpoints

Overall Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year
Baseline to 1-year

Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.

Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score <69
Baseline to 1-year

Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.

Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69
Baseline to 1-year

Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.

Percentage of Participants Who Improved by ≥2 Steps From Baseline in the Diabetic Retinopathy Disease Severity Scale (DRSS) Score at Week 24 in the Combined 2Q16 and 2Q8 Groups
At Week 24

The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 24 from baseline.

Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
At Week 52

The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 52 from baseline.

Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD
Baseline (day 1) through end of treatment (Week 180)

The primary endpoint in the study is the safety and tolerability of Intravitreal Aflibercept Injection in patients with neovascular AMD (Age-related Macular Degeneration) from day 1 through the end of treatment visit (week 180) based on the number of participants who experienced any treatment-emergent adverse event (TEAE). Treatment-emergent adverse events were categorized according to Ocular TEAEs in the study eye, Ocular TEAEs in the fellow eye, and Non-Ocular TEAEs

Percentage of Subjects Converting to Exudative AMD at 24 Months.
24 months

Percentage of subjects converting to exudative AMD at 24 months as confirmed by independent masked reading center.

Incidence and severity of adverse events of intravitreal aflibercept injection in the treatment of PDR.
The primary endpoint of the study will be at week 52.
Safety of Intravitreal Aflibercept Injection
6 months

Safety will be measured by the amount, significance and details of adverse events/reactions to the study drug.

Change in BCVA From Baseline to Week 24 - Last Observation Carried Forward (LOCF)
At week 24

Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Measurements were taken at every study visit. Missing values were imputed with post-baseline values during on-treatment period by using last observation carried forward (LOCF).

Mean Change in Capillary Non-Perfusion
12 months

To determine mean change in the presence and amount of capillary non-perfusion as measured by wide-angle angiography using Optos 200Tx system at Baseline, Month 3, Month 6, and Month 12.

Secondary Endpoints

Overall Change in Optical Coherence Tomography Central Subfield Thickness
baseline to 1-year
Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score <69
baseline to 1-year
Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score 78-69
baseline to 1-year
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Study Design & Arms

AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
RanibizumabACTIVE_COMPARATOR -
AfliberceptEXPERIMENTAL -
BevacizumabEXPERIMENTAL -
Dosing regimen 1EXPERIMENTALParticipants will receive IVT aflibercept dosing regimen 1
Dosing regimen 2EXPERIMENTALParticipants will receive IVT aflibercept dosing regimen 2
Dosing regimen 3SHAM_COMPARATORParticipants will receive matching sham injections
Open-label Intravitreal Aflibercept InjectionEXPERIMENTALOpen-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
Intravitreal aflibercept injectionEXPERIMENTALSubjects will be randomized to receive intravitreal aflibercept injection every three months for 24 months.
PlaceboPLACEBO_COMPARATORSubjects will be randomized to receive sham injection every three months for 24 months.
Group A - IAI every 4 weeksEXPERIMENTALReceives 5 injections of Intravitreal Aflibercept Injection (IAI) beginning Day 1, and then at weeks 4, 8, 12, and 16. Following the 5 initial injections, this group will continue to receive IAI every 4 weeks, beginning week 20, through week 48.
Group B - IAI every 8 weeksEXPERIMENTALReceives 5 injections of Intravitreal Aflibercept Injection (IAI) beginning Day 1, and then at weeks 4, 8, 12, and 16. Following the 5 initial injections, this group will receive IAI every 8 weeks, beginning week 24, through week 48.
Intravitreal Aflibercept Injection (x4)EXPERIMENTAL2 mg / Intravitreal / every 1 month x 3 months and at month 4 (Drug administered 4 times).
Intravitreal Aflibercept Injection (x6)EXPERIMENTAL2 mg / Intravitreal / every 1 month x 6 months ((Drug administered 6 times).
Intravitreal Aflibercept Injection .5Q4EXPERIMENTALIntravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) .5 mg every 4 weeks
Intravitreal Aflibercept Injection 2Q4EXPERIMENTALIntravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2 mg every 4 weeks
Intravitreal Aflibercept Injection 2Q8EXPERIMENTALIntravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2mg every 4 weeks for 3 visits followed by every 8 weeks
Intravitreal Aflibercept Injection 2PRNEXPERIMENTALIntravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2mg every 4 weeks for 3 visits followed by PRN (as-needed) dosing according to the re-treatment criteria
Laser PhotocoagulationACTIVE_COMPARATORFocal laser at week 1, and one week after visits at which the participant met laser re-treatment criteria to the end of the study (week 52) starting at week 16; laser re- treatment was permitted no more than once every 16 weeks.
Every Month TreatmentEXPERIMENTALPatients will receive Intravitreal Aflibercept Injection (IAI) every month for the 12 month duration of the study.
Every Month, then Every Other MonthEXPERIMENTALPatients will receive Intravitreal Aflibercept Injection (IAI) every month for the first 6 months, then every other month for the next 6 months. Retreatment criteria will allow for patients to be treated every month in the second 6 months if needed.

Interventions

NameTypeDescription
2.0 mg intravitreal afliberceptDRUGIntravitreal injection of 2.0 mg aflibercept at baseline and up to every 4 weeks using defined retreatment criteria.
1.25 mg intravitreal bevacizumabDRUGIntravitreal injection of 1.25 mg bevacizumab at baseline and up to every 4 weeks using defined retreatment criteria.
0.3 mg intravitreal ranibizumabDRUGIntravitreal injection of 0.3 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.
Intravitreal aflibercept injection [IAI]DRUG -
ShamDRUG -
Intravitreal Aflibercept Injection 2mgDRUG -
Intravitreal aflibercept injectionDRUGIntravitreal aflibercept injection
PlaceboDRUGSham injection
Intravitreal Aflibercept Injection (IAI)DRUGEYLEA (aflibercept) is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary (CHO) cells.
Laser PhotocoagulationPROCEDURElaser every 16 weeks as needed
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites90

Inclusion Criteria: * Age ≥ 18 years * Individuals \<18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable. * Diagnosis of diabetes mellitus (type 1 or type 2) * Any one of the following will be considered to be sufficient evidenc...

Countries:United StatesGermanyHungaryJapanPuerto RicoUnited KingdomCanadaAustria
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Frequently asked questions about Intravitreal Aflibercept

What is Intravitreal Aflibercept used for?

Intravitreal Aflibercept is an investigational small molecule being developed for ophthalmology indications including Central Retinal Vein Occlusion, Central Serous Chorioretinopathy, Nonproliferative Diabetic Retinopathy, Neovascular Age-related Macular Degeneration, Proliferative Diabetic Retinopathy, and Diabetic Macular Edema. It is administered by intravitreal injection and is currently in Phase 1 clinical development.

Who makes Intravitreal Aflibercept?

Intravitreal Aflibercept is being developed by Regeneron Pharmaceuticals, Inc., which trades on the NASDAQ under the ticker REGN. The company is conducting clinical trials of this investigational therapy for multiple retinal and macular conditions.

What phase is Intravitreal Aflibercept in?

Intravitreal Aflibercept is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. The FDA has granted it Priority Review designation, though it remains in clinical trials and is not yet available as a marketed therapy.

What clinical trials is Intravitreal Aflibercept in?

Intravitreal Aflibercept has completed two clinical trials: NCT00789477, a Phase 2 study in Diabetic Macular Edema with 221 participants, and NCT00964795, a Phase 3 open-label extension in Neovascular Age-related Macular Degeneration with 323 participants. Both trials are completed.

Is Intravitreal Aflibercept the same as EYLEA?

Yes, Intravitreal Aflibercept is also known as EYLEA and BAY86-5321. Clinical trial records refer to it as Intravitreal Aflibercept Injection (IAI; EYLEA; BAY86-5321), confirming these names refer to the same drug being developed by Regeneron.