Eylea (aflibercept) - 4 indications

Scroll down for information on each indication:

• neovascular (wet) age-related macular degeneration; approved November 2011
• macular edema following retinal vein occlusion; approved September 2012
• diabetic macular edema; approved July 2014
• diabetic retinopathy; approved March 2015

General Information

Eylea (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor.

Eylea is supplied as a solution for intravitreal injection. Scroll down for dosing and administration recommendations for each therapeutic condition.

Mechanism of Action

Eylea (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor. Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes. Activation of these receptors by VEGF-A can result in neovascularization and vascular permeability. Aflibercept acts as a soluble decoy receptor that binds VEGF-A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors.

Side Effects

Adverse effects associated with the use of Eylea may include, but are not limited to, the following:

• conjunctival hemorrhage
• eye pain
• cataract
• vitreous detachment
• vitreous floaters
• intraocular pressure increased

Indication 1 - neovascular (wet) age-related macular degeneration

approved November 2011

Dosing/Administration

The recommended dose is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).

Although Eylea may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when Eylea was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 12 weeks (3 months).

Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly.

Clinical Trial Results

The FDA Approval of Eylea was based on two randomized, multi-center, double-masked, active-controlled studies, VIEW1 and VIEW2. A total of 2,412 subjects were treated and evaluable for efficacy. The subjects were randomized to one of four dosing regimens: 1) Eylea administered 2 mg every 8 weeks following three initial monthly doses (Eylea 2Q8); 2) Eylea administered 2 mg every four weeks (Eylea 2Q4); 3) Eylea 0.5 mg administered every four weeks (Eylea 0.5Q4); and 4) ranibizumab administered 0.5 mg every four weeks (ranibizumab 0.5 mg Q4). The primary efficacy endpoint was the proportion of subjects who maintained vision, defined as losing fewer than 15 letters of visual acuity at week 52 compared to baseline. Both Eylea 2Q8 and 2Q4 groups were shown to have efficacy that was clinically equivalent to the ranibizumab 0.5 mg Q4 group. In VIEW1 this endpoint was reached by 94%, 95% and 94% of subjects in the Eylea 2Q8, Eylea 2Q4 and ranibizumab arms, respectively. In VIEW2 this endpoint was reached by 95% of subjects in all three treatment arms.

Indication 2 - macular edema following retinal vein occlusion

approved September 2012

Dosing/Administration

The recommended dose is 2 mg (0.05 mL) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly).

Clinical Trial Results

The FDA approval of Eylea for the treatment of macular edema following Central Retinal Vein Occlusion (CRVO) was based on two randomized, multi-center, double-masked, sham-controlled studies: COPERNICUS (Controlled Phase 3 Evaluation of Repeated intravitreal administration of VEGF Trap-Eye In Central retinal vein occlusion: Utility and Safety) and GALILEO (General Assessment Limiting Infiltration of Exudates in central retinal vein Occlusion with EYLEA). A total of 358 patients were treated and evaluable for efficacy. In both studies, patients were randomly assigned in a 3:2 ratio to either 2 mg Eylea administered every 4 weeks (Q4), or sham injections (control group) administered every 4 weeks for a total of 6 injections.  After 6 monthly injections, patients continued to receive Eylea treatment during weeks 24 to 52 only if they met pre-specified retreatment criteria (PRN), except for patients in the sham control group in the GALILEO study who continued to receive sham injections through week 52.  Patients ranged in age from 22 to 89 years with a mean of 64 years. In the COPERNICUS study, after six months, 56% of patients receiving Eylea 2 mg monthly gained at least 15 letters of Best Corrected Visual Acuity (BCVA) from baseline, as measured by ETDRS, compared to 12% of patients receiving sham injections (p < 0.01), the primary endpoint of the study. In the GALILEO study, after six months, 60% of patients receiving Eylea 2 mg monthly for the first 6 months, gained at least 15 letters of BCVA from baseline, compared to 22% of patients receiving sham injections during this time, the primary endpoint of the study.  

The FDA approval of Eylea for Branch Retinal Vein Occlusion was based on the double-masked, randomized, controlled Phase 3 VIBRANT study of 181 patients with Macular Edema following BRVO. The VIBRANT study compared Eylea 2 mg once every 4 weeks with macular laser photocoagulation (control).  At 24 weeks, significantly more patients treated with Eylea gained at least 15 letters in vision (three lines on an eye chart) from baseline as measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, the primary endpoint of the study, compared with patients who received control (53 percent vs. 27 percent).

Indication 3 - diabetic macular edema

approved July 2014

Dosing/Administration

The recommended dose is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).

Although Eylea may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when Eylea was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months).

Clinical Trial Results

The FDA approval of Eylea in DME was based on the one-year data from the Phase 3 VISTA-DME and VIVID-DME studies of 862 patients, which compared Eylea 2 mg given monthly, Eylea 2 mg given every two months (after five initial monthly injections), or macular laser photocoagulation (at baseline and then as needed). In the DME studies, after one year, the mean changes in Best Corrected Visual Acuity (BCVA), as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart for the monthly and every two month Eylea groups, were statistically significantly improved compared to the control group and were similar to each other. Across both trials, patients in both Eylea dosing groups gained, on average, the ability to read approximately two additional lines on an eye chart compared with almost no change in the control group.

Indication 4 - diabetic retinopathy

approved March 2015

Dosing/Administration

The recommended dose is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).

Although Eylea may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when Eylea was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months).

Clinical Trial Results

The FDA approval of Eylea for the treatment of diabetic retinopathy in DME was based on two year data from the Phase III VISTA-DME and VIVID-DME studies of 862 patients, which compared Eylea 2 mg monthly, Eylea 2 mg every two months (after five initial monthly injections), or macular laser photocoagulation (at baseline and then as needed).  In these studies, on the primary endpoint of mean change in Best Corrected Visual Acuity (BCVA) at one year, patients treated with Eylea monthly or every two months showed statistically significant improvements compared to the control group. Patients in both Eylea groups gained, on average, the ability to read approximately two additional lines on an eye chart compared with almost no change in the control group.

The FDA approval of Eylea for diabetic retinopathy was based on six-month and one-year results from PANORAMA, a randomized, multi-center, controlled Phase 3 trial that enrolled 402 patients and was designed to investigate Eylea for the improvement of moderately severe to severe NPDR without diabetic macular edema (DME), compared to sham injection. There were three treatment arms – an observational sham injection group and two Eylea treatment groups. Eylea was dosed every eight weeks (following five initial monthly doses) or every 16 weeks (following three initial monthly doses and one eight-week interval). The primary endpoint was the proportion of patients who experienced a two-step or greater improvement in the diabetic retinopathy severity scale (DRSS) from baseline for the combined Eylea treatment groups at week 24, and for each Eylea treatment group separately (every eight-week group and every 16-week group) at week 52. The DRSS is a systematic grading scale to assess DR severity based on photographs of the retina.