EYLEA Rx

Neovascular (Wet) Age-Related Macular Degeneration (AMD)

• The safety and efficacy of Eylea were assessed in two randomized, multi-center, double-masked, active-controlled studies (VIEW1 and VIEW2) in a total of 2412 patients with wet AMD. In each study, up to week 52, patients were randomly assigned in a 1:1:1:1 ratio to 1 of 4 dosing regimens: 1) Eylea administered 2 mg every 8 weeks following 3 initial monthly doses (Eylea 2Q8); 2) Eylea administered 2 mg every 4 weeks (Eylea 2Q4); 3) Eylea 0.5 mg administered every 4 weeks (Eylea 0.5Q4); and 4) ranibizumab administered 0.5 mg every 4 weeks (ranibizumab 0.5 mg Q4). The primary efficacy endpoint for both studies was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at week 52 compared to baseline.
• In VIEW1, 94% and 95% of patients treated with Eylea 2Q8 and Eylea 2Q4, respectively, maintained vision compared with 94% of those treated with ranibizumab. The mean change in best corrected visual acuity (BVCA) as measured by early treatment diabetic retinopathy study (ETDRS) letter score from baseline was 7.9 for Eylea 2Q8 and 10.9 for Eylea 2Q4 compared with 8.1 for ranibizumab. The number of patients who gained at least 15 letters of vision from baseline were: 92 for Eylea 2Q8, 114 for Eylea 2Q4, and 94 for ranibizumab.
• In VIEW2, 95% and 95% of patients treated with Eylea 2Q8 and Eylea 2Q4, respectively, maintained vision compared with 95% of those treated with ranibizumab. The mean change in BVCA as measured by ETDRS letter score from baseline was 8.9 for Eylea 2Q8 and 7.6 for Eylea 2Q4 compared with 9.4 for ranibizumab. The number of patients who gained at least 15 letters of vision from baseline were: 96 for Eylea 2Q8, 91 for Eylea 2Q4, and 99 for ranibizumab.
• VIEW1 and VIEW2 studies were both 96 weeks in duration. However after 52 weeks patients no longer followed a fixed dosing schedule. Between week 52 and week 96, patients continued to receive the drug and dosage strength to which they were initially randomized on a modified 12 week dosing schedule (doses at least every 12 weeks and additional doses as needed). Therefore, during the second year of these studies there was no active control comparison arm.

Macular Edema Following Central Retinal Vein Occlusion (CRVO)

• The safety and efficacy of Eylea were assessed in two randomized, multicenter, double-masked, sham-controlled studies (COPERNICUS and GALILEO) in a total of 358 patients with macular edema following CRVO. In both studies, patients were randomly assigned in a 3:2 ratio to either 2 mg Eylea administered every 4 weeks (2Q4), or sham injections (control group) administered every 4 weeks for a total of 6 injections. The primary efficacy endpoint for both studies was the proportion of patients who gained at least 15 letters in BCVA compared to baseline.  
• In COPERNICUS, 56% of patients treated with Eylea gained at least 15 letters in BCVA compared with 12% of patients in the control group (weighted difference, 44.8%; 95.1% CI, 32.9-56.6; P <.01). The mean change in BCVA as measured by ETDRS letter score from baseline was 17.3 for Eylea and -4.0 for the control group (difference in least squares [LS] mean, 21.7; 95.1% CI, 17.3-26.1; P <.01).
• In GALILEO, 60% of patients treated with Eylea gained at least 15 letters in BCVA compared with 22% of patients in the control group (weighted difference, 38.3%; 95.1% CI, 24.4-52.1; P <.01). The mean change in BCVA as measured by ETDRS letter score from baseline was 18.0 for Eylea and 3.3 for the control group (difference in LS mean, 14.7; 95.1% CI, 10.7-18.7; P <.01).

Macular Edema Following Branch Retinal Vein Occlusion (BRVO)  

• The safety and efficacy of Eylea were assessed in the 24-week, randomized, multi-center, double-masked, controlled VIBRANT study in a total of 181 patients with macular edema following BRVO. Patients were randomly assigned in a 1:1 ratio to either 2 mg Eylea administered every 4 weeks (2Q4) or laser photocoagulation administered at baseline and subsequently as needed (control group). The primary efficacy endpoint was the proportion of patients who gained at least 15 letters in BCVA at week 24 compared to baseline.
• Results showed that 52.7% of patients treated with Eylea gained at least 15 letters in BCVA from baseline compared with 26.7% of patients in the control group (weighted difference, 26.6%; 95% CI, 13.0-40.1; P <.01). The mean change in BCVA as measured by ETDRS letter score from baseline was 17.0 for Eylea and 6.9 for the control group (difference in LS mean, 10.5; 95% CI, 7.1-14.0; P <.01).

Diabetic Macular Edema (DME)

• The safety and efficacy of Eylea were assessed in two randomized, multi-center, double-masked, controlled studies (VIVID and VISTA) in a total of 862 patients with DME. In each study, patients were randomly assigned in a 1:1:1 ratio to 1 of 3 dosing regimens: 1) Eylea administered 2 mg every 8 weeks following 5 initial monthly injections (Eylea 2Q8); 2) Eylea administered 2 mg every 4 weeks (Eylea 2Q4); and 3) macular laser photocoagulation (at baseline and then as needed).
• Beginning at week 24, patients meeting a pre-specified threshold of vision loss were eligible to receive additional treatment: patients in the Eylea groups could receive laser and patients in the laser group could receive Eylea. The primary efficacy endpoint for both studies was the mean change from baseline in BCVA at week 52 as measured by ETDRS letter score.
• At week 52 for VIVID, the mean change in BCVA as measured by ETDRS letter score from baseline was 10.7 for Eylea 2Q8 (difference in LS mean, 9.1; 97.5% CI, 6.3-11.8; P <.01) and 10.5 for Eylea 2Q4 (difference in LS mean, 9.3; 97.5% CI, 6.5-12.0; P <.01) compared with 1.2 for the control group. Moreover, 33.3% and 32.4% of patients treated with Eylea 2Q8 and Eylea 2Q4 gained at least 15 letters in BCVA from baseline compared with 9.1% of those treated with control (both P <.01). 
• At week 100 for VIVID, the mean change in BCVA as measured by ETDRS letter score from baseline was 9.4 for Eylea 2Q8 (difference in LS mean, 8.2; 97.5% CI, 5.2-11.3; P <.01) and 11.4 for Eylea 2Q4 (difference in LS mean, 10.7; 97.5% CI, 7.6-13.8; P <.01) compared with 0.7 for the control group. Moreover, 31.1% and 38.2% of patients treated with Eylea 2Q8 and Eylea 2Q4 gained at least 15 letters in BCVA from baseline compared with 12.1% of those treated with control (both P <.01). 
• At week 52 for VISTA, the mean change in BCVA as measured by ETDRS letter score from baseline was 10.7 for Eylea 2Q8 (difference in LS mean, 10.5; 97.5% CI, 7.7-13.2; P <.01) and 12.5 for Eylea 2Q4 (difference in LS mean, 12.2; 97.5% CI, 9.4-15.0; P <.01) compared with 0.2 for the control group. Moreover, 31.1% and 41.6% of patients treated with Eylea 2Q8 and Eylea 2Q4 gained at least 15 letters in BCVA from baseline compared with 7.8% of those treated with control (both P <.01). 
• At week 100 for VISTA, the mean change in BCVA as measured by ETDRS letter score from baseline was 11.1 for Eylea 2Q8 (difference in LS mean, 10.1; 97.5% CI, 7.0-13.3; P <.01) and 11.5 for Eylea 2Q4 (difference in LS mean, 10.6; 97.5% CI, 7.1-14.2; P <.01) compared with 0.9 for the control group. Moreover, 33.1% and 38.3% of patients treated with Eylea 2Q8 and Eylea 2Q4 gained at least 15 letters in BCVA from baseline compared with 13.0% of those treated with control (both P <.01). 
• Treatment effects in the subgroup of patients who had previously been treated with a VEGF inhibitor prior to study participation were similar to those seen in patients who were VEGF inhibitor naïve prior to study participation.

Diabetic Retinopathy (DR)  

Efficacy and safety data of Eylea in diabetic retinopathy (DR) are derived from the VIVID, VISTA, and PANORAMA studies.

VIVID and VISTA

• In the VIVID and VISTA studies, an efficacy outcome was the change in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (ETDRS-DRSS). The ETDRS-DRSS score was assessed at baseline and approximately every 6 months thereafter for the duration of the studies. At week 100, the proportion of patients improving by at least 2 steps on the ETDRS-DRSS was significantly greater in both Eylea treatment groups (2Q4 and 2Q8) when compared to the control group.
• In VIVID, 32% (n=32/101) and 27% (n=27/97) of patients treated with Eylea 2Q8 and Eylea 2Q4, respectively, improved by at least 2 steps on the ETDRS-DRSS at week 100 from baseline compared with 7% (n=7/99) of those in the control group (both P <.01).
• In VISTA, 38% (n=56/148) and 38% (n=58/153) of patients treated with Eylea 2Q8 and Eylea 2Q4, respectively, improved by at least 2 steps on the ETDRS-DRSS at week 100 from baseline compared with 16% (n=24/150) of those in the control group (both P <.01).

PANORAMA

• The randomized, multicenter, double-masked, controlled PANORAMA study assessed the safety and efficacy of Eylea in a total of 402 patients with moderately severe to severe nonproliferative diabetic retinopathy (NPDR) (ETDRS-DRSS of 47 or 53), without central-involved DME (CI-DME). Patients were randomly assigned in a 1:1:1 ratio to 1 of 3 dosing regimens: 1) 3 initial monthly Eylea 2 mg injections followed by one injection after 8 weeks and then one injection every 16 weeks (Eylea 2Q16); 2) 5 monthly Eylea 2 mg injections followed by one injection every 8 weeks (Eylea 2Q8); and 3) sham treatment.
• The primary efficacy endpoint was the proportion of patients who improved by ≥2 steps on the DRSS from baseline to week 24 in the combined Eylea groups and at week 52 in the 2Q16 and 2Q8 groups individually versus sham. A key secondary endpoint was the proportion of patients developing the composite endpoint of proliferative diabetic retinopathy or anterior segment neovascularization through week 52.  
• At week 24, results showed that 58% of patients in the combined Eylea groups achieved at least a 2-step improvement on ETDRS-DRSS from baseline compared with 6% of those in the control group (adjusted difference, 52%; 95% CI, 45-60; P <.01). 
• At week 52, results showed that 65% and 80% of patients treated with Eylea 2Q16 (adjusted difference, 50%; 95% CI, 40-60; P <.01) and Eylea 2Q8 (adjusted difference, 65%; 95% CI, 56-74; P <.01), respectively, achieved at least a 2-step improvement on ETDRS-DRSS from baseline compared with 15% of those in the control group.

Retinopathy of Prematurity (ROP)

• Efficacy and safety data of Eylea in ROP are derived from the BUTTERFLEYE (N=113) and FIREFLEYE (N=120) studies.
• Study participants had a maximum gestational age at birth of 32 weeks or a maximum birth weight of 1500g, had to weigh at least 800g on the day of treatment and had treatment-naïve ROP.
• Patients were randomly assigned to receive 0.4mg of aflibercept via intravitreal injection or laser photocoagulation (the standard treatment for ROP). The primary endpoint was the proportion of patients with absence of active ROP and unfavorable structural outcomes at week 52 of chronological age. 
• Findings from both trials showed that approximately 80% of patients who received aflibercept achieved an absence of active ROP and unfavorable structural outcomes at 52 weeks of age. However, the trials failed to meet the primary endpoint of noninferiority due to laser photocoagulation achieving comparable levels of efficacy, which were higher than previously seen in similar ROP trials.