Proven Visual Outcomes, Fewer Injections With EYLEA Q8 vs Ranibizumab Q4

Demonstrated in the largest phase 3 anti-VEGF trials completed to date in Wet Age-Related Macular Degeneration (N=2412)1-4

Vision maintained at Year 1 with ≈5 fewer injections with EYLEA Q8 vs ranibizumab Q4

Proportion of patients who maintained vision (<15 ETDRS letters lost of BCVA) at Year 1 from baseline1-3,*

In the VIEW 1 study: EYLEA Q4 (n=304), 95% with an average of 12.5 injections; EYLEA Q8 (n=301), 94% with an average of 7.5 injections; ranibizumab Q4 (n=304), 94% with an average of 12.1 injections. In the VIEW 2 study: EYLEA Q4 (n=309), 95% with an average of 12.6 injections; EYLEA Q8 (n=306), 95% with an average of 7.7 injections; ranibizumab Q4 (n=291), 95% with an average of 12.7 jnjections. In the VIEW 1 study: EYLEA Q4 (n=304), 95% with an average of 12.5 injections; EYLEA Q8 (n=301), 94% with an average of 7.5 injections; ranibizumab Q4 (n=304), 94% with an average of 12.1 injections. In the VIEW 2 study: EYLEA Q4 (n=309), 95% with an average of 12.6 injections; EYLEA Q8 (n=306), 95% with an average of 7.7 injections; ranibizumab Q4 (n=291), 95% with an average of 12.7 jnjections.

EYLEA was clinically equivalent to ranibizumab.

Proportion of patients who maintained vision (<15 ETDRS letters lost of BCVA) at Year 2 from baseline1,2,*

In VIEW 1 and VIEW 2, 92% of patients on EYLEA ≤Q12 (n=613) maintained vision; 92% of patients on EYLEA ≤Q12 (n=607) maintained vision; 92% of patients on ranibizumab ≤Q12 (n=595) maintained vision. In VIEW 1 and VIEW 2, 92% of patients on EYLEA ≤Q12 (n=613) maintained vision; 92% of patients on EYLEA ≤Q12 (n=607) maintained vision; 92% of patients on ranibizumab ≤Q12 (n=595) maintained vision. In VIEW 1 and VIEW 2, 92% of patients on EYLEA ≤Q12 (n=613) maintained vision; 92% of patients on EYLEA ≤Q12 (n=607) maintained vision; 92% of patients on ranibizumab ≤Q12 (n=595) maintained vision.

The results of these exploratory endpoints require cautious interpretation and could represent chance findings, as a multiplicity
adjustment has not been applied.

VIEW 1 and VIEW 2 Study
Designs

Two multicenter, double-masked clinical studies in which patients with Wet AMD (N=2412; age range: 49-99 years, with a mean of 76 years) were randomized to receive: 1) EYLEA 2 mg Q8 following 3 initial monthly doses; 2) EYLEA 2 mg Q4; 3) EYLEA 0.5 mg Q4; or 4) ranibizumab 0.5 mg Q4. Protocol-specified visits occurred every 28 (±3) days.1

In both studies, the primary efficacy endpoint was the proportion of patients with Wet AMD who maintained vision, defined as losing <15 letters of visual acuity at Week 52, compared with baseline.1

Between Week 52 and Week 96, all patients received the same study drug and dosage strength as in the first 52 weeks but continued on a
regimen where dosing could be extended up to Q12, based on monthly investigator assessments of prespecified visual and anatomic outcomes.
There was no active control comparison group that received a fixed dosing regimen in Year 2. Patients were re-treated if ≥1 of the following
criteria were met: 1) loss of ≥5 letters of visual acuity from best previous score with recurrent fluid on TD-OCT; 2) new or persistent fluid (any new
or unchanged cystic retinal edema and/or subretinal fluid) on TD-OCT; 3) new or persistent leakage on fluorescein angiography; 4) new macular hemorrhage; 5) new-onset classic neovascularization; 6) increase in CST of ≥100 μm (cystic retinal edema and/or subretinal fluid meeting a
specific quantitative thickening threshold), as measured by TD-OCT, compared with lowest previous value; 7) time lapse of ≥12 weeks since
previous injection.2

Efficacy endpoints evaluated after Week 52 were exploratory and included the proportion of patients maintaining visual acuity, the mean change
in BCVA from baseline, and the proportion of patients gaining ≥15 letters.2

anti-VEGF, anti–vascular endothelial growth factor; BCVA, best-corrected visual acuity; CST, central subfield thickness; ETDRS, Early Treatment Diabetic Retinopathy Study; Q4, every
4 weeks; Q8, every 8 weeks; Q12, every 12 weeks; TD-OCT, time domain–optical coherence tomography.

Rapid and Largely Sustained Visual Improvements

Integrated VIEW 1 and VIEW 2
Mean change in BCVA (ETDRS letters) through Years 1 and 2 from baseline2,3,*

EYLEA Q4 (Year 1):+9.3 letters with an average of 12.3 injections, and EYLEA ≤Q12 (Year 2) (n=613): +7.6 letters, with 4.7 additional injections. EYLEA Q8 (Year 1): +8.4 letters with an average of 7.5 injections, and ≤Q12 (Year 2) (n=607): +7.6 letters, with 4.2 additional injections. Ranibizumab Q4 (Year 1): +8.7 letters with an average of 12.3 injections, and Ranibizumab ≤Q12 (year 2): +7.9 letters with 4.7 additional injections. EYLEA Q4 (Year 1):+9.3 letters with an average of 12.3 injections, and EYLEA ≤Q12 (Year 2) (n=613): +7.6 letters, with 4.7 additional injections. EYLEA Q8 (Year 1): +8.4 letters with an average of 7.5 injections, and ≤Q12 (Year 2) (n=607): +7.6 letters, with 4.2 additional injections. Ranibizumab Q4 (Year 1): +8.7 letters with an average of 12.3 injections, and Ranibizumab ≤Q12 (year 2): +7.9 letters with 4.7 additional injections.
  • All treatment groups were extended to a Q12 dosing schedule in Year 2, with the option of more frequent dosing based on the physician’s monthly assessment of anatomic and visual outcomes. Therefore, there was no active control comparison group in Year 2.
  • In the VIEW 1 and 2 studies, vision gains in the EYLEA Q4 and Q8 groups decreased, on average, by 1 to 2 letters at Year 2 compared with Year 1

BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; Q4, every 4 weeks; Q8, every 8 weeks; Q12, every 12 weeks.

Patients Whose Dosing Interval Was Extended to EYLEA Q12 Largely Sustained Their BCVA Gains

Approximately half of EYLEA patients were on Q12 in Year 2 after a year of effective therapy

In a post hoc subgroup analysis, based on physician assessment of prespecified visual and anatomic outcomes
from Year 1 to Year 2 (52-96 weeks)5

The analyses of post hoc endpoints were not multiplicity protected and are descriptive only.

  • Approximately 4% of patients were dosed outside the Q12 window5

Eligibility to maintain Q12 dosing in Year 2 was based on stringent re-treatment criteria5

Patients were re-treated if ≥1 of the following criteria were met
  • Time lapse of ≥12 weeks since previous injection
Visual and anatomic criterion
  • Loss of ≥5 ETDRS letters from best previous score with recurrent fluid*
Anatomic criteria
  • New or persistent retinal fluid*
  • Increase in CST* of ≥100 μm vs the lowest previous value
  • New-onset classic neovascularization
  • New macular hemorrhage
  • New or persistent leakage on fluorescein angiography
  • After Year 1, dosing schedules for all treatment groups were extended to
    Q12, with monthly evaluations for re-
    treatment based on prespecified visual
    and anatomic outcomes during Year 2.
    Therefore, there was no active control
    comparison group during Year 21,5
  • Although not as effective as the
    recommended Q8 dosing regimen,
    patients may be treated with EYLEA
    Q12 after 1 year of effective therapy.
    Patients should be assessed regularly1

BCVA, best-corrected visual acuity; CST, central subfield thickness; ETDRS, Early Treatment Diabetic Retinopathy Study; Q8, every 8 weeks; Q12, every 12 weeks; TD-OCT, time
domain–optical coherence tomography.

Largely Sustained Vision Gains With Less Frequent Dosing (Q12) in Year 2

Integrated VIEW 1 and VIEW 2 (post hoc subgroup analysis)
Mean change in BCVA (ETDRS letters) through Years 1 and 2 from baseline3,5,*

EYLEA Q4 (Year 1):+9.9 letters with an average of 12.3 injections, and EYLEA Q12 (Year 2) (n=284): +8.8 letters, with 54% of patients only on Q12 (+3 injections from Year 1). EYLEA Q8 (Year 1): +9.7 letters with an average of 7.5 injections, and Q12 (Year 2) (n=245): +9.2 letters, with 48% of patients only on Q12 (+3 injections from Year 1). Ranibizumab Q4 (Year 1): +8.7 letters with an average of 12.3 injections, and Ranibizumab Q12 (year 2): +8.5 letters with 43% of patients only on Q12 (+3 injections from Year 1). EYLEA Q4 (Year 1):+9.9 letters with an average of 12.3 injections, and EYLEA Q12 (Year 2) (n=284): +8.8 letters, with 54% of patients only on Q12 (+3 injections from Year 1). EYLEA Q8 (Year 1): +9.7 letters with an average of 7.5 injections, and Q12 (Year 2) (n=245): +9.2 letters, with 48% of patients only on Q12 (+3 injections from Year 1). Ranibizumab Q4 (Year 1): +8.7 letters with an average of 12.3 injections, and Ranibizumab Q12 (year 2): +8.5 letters with 43% of patients only on Q12 (+3 injections from Year 1).

The analyses of these post hoc endpoints were not multiplicity protected and are descriptive only.

BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; Q4, every 4 weeks; Q8, every 8 weeks; Q12, every 12 weeks.

EYLEA—Long-term Vision Gains at Year 4 From the VIEW 1 Baseline

VIEW 1 Extension
Mean change in BCVA (ETDRS letters) through Year 4 (212 weeks) from the VIEW 1 baseline6,*

In the VIEW 1 study, patients gained +10.4 letters at Year 1, +10.2 letters at Year 2, and +7.1 letters at Year 4. In the VIEW 1 study, patients gained +10.4 letters at Year 1, +10.2 letters at Year 2, and +7.1 letters at Year 4.
  • The VIEW 1 Extension included patients switched at Year 2 from the ranibizumab treatment arm in VIEW 16
  • VIEW 1 had fixed dosing through Year 1, followed by modified quarterly dosing (≤Q12) through Year 2. In the VIEW 1 Extension, all patients received EYLEA 2 mg on a modified quarterly dosing schedule (≤Q12), later amended to dosing at least Q8 through Year 46
No new safety signals compared with the known profile of EYLEA in Wet AMD.6

Vision maintained* or gained at Year 4 from VIEW 1 baseline6,†

The analyses of these endpoints were not multiplicity protected and are descriptive only.

VIEW 1 Extension Study Design

Prospective, open-label, single-arm, multicenter, long-term safety and tolerability study of patients who completed VIEW 1 through Week 96
(n=323; mean age: 79 years). All patients received EYLEA 2 mg on a modified quarterly dosing schedule (maximum treatment interval: Q12) that
was later amended to dosing at least Q8 through Week 212.3

The primary endpoint was the safety and tolerability of EYLEA.3

First-line EYLEA Demonstrated Consistent Results Regardless of Baseline Vision

Integrated VIEW 1 and VIEW 2 (prespecified subgroup analysis)
Proportion of patients who gained or maintained vision (<15 ETDRS letters lost) at Year 1 by baseline BCVA3

<20/200 (<35 letters): EYLEA Q4 (n=61/61) was 100%; EYLEA Q8 (n=68/69) was 99%; ranibizumab Q4 (n=72/75) was 96%. 20/200 to 20/100 ( ≥35 letters to <50 letters): EYLEA Q4 (n=121/128) was 95%; EYLEA Q8 (n=125/132) was 95%; ranibizumab Q4 (n=91/97) was 94%.  ≥20/100 ( ≥50 letters): EYLEA Q4 (n=121/128) was 94%; EYLEA Q8 (n=383/406) was 94%; ranibizumab Q4 (n=398/423) was 94%. <20/200 (<35 letters): EYLEA Q4 (n=61/61) was 100%; EYLEA Q8 (n=68/69) was 99%; ranibizumab Q4 (n=72/75) was 96%. 20/200 to 20/100 ( ≥35 letters to <50 letters): EYLEA Q4 (n=121/128) was 95%; EYLEA Q8 (n=125/132) was 95%; ranibizumab Q4 (n=91/97) was 94%.  ≥20/100 ( ≥50 letters): EYLEA Q4 (n=121/128) was 94%; EYLEA Q8 (n=383/406) was 94%; ranibizumab Q4 (n=398/423) was 94%.

The results of this prespecified subgroup analysis require cautious interpretation and could represent chance findings, as a multiplicity
adjustment has not been applied.

Treatment effects in evaluable subgroups in each study were, in general, consistent with the results in the overall populations.1,3

EYLEA Q4 Is FDA Approved for Patients Who May Need More Frequent Injections

  • Although EYLEA may be dosed as frequently as 2 mg Q4 (~every 25 days, monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed Q4 compared with Q8. Some patients need Q4 (monthly) dosing after the first 12 weeks (3 months)1

Integrated VIEW 1 and VIEW 2 (post hoc analysis)
Mean change in BCVA (ETDRS letters) through Year 1 from baseline in patients with or without early persistent retinal fluid7

In patients with early persistent retinal fluid, patients on EYLEA Q4 (n=115) +11.7 letters and patients on EYLEA Q8 (n=123) +7.5 letters. In patients without persistent early retinal fluid, patients on EYLEA Q4 (n=498) +8.9 letters, and patients on EYLEA Q8 (n=484) +9.8 letters. In patients with early persistent retinal fluid, patients on EYLEA Q4 (n=115) +11.7 letters and patients on EYLEA Q8 (n=123) +7.5 letters. In patients without persistent early retinal fluid, patients on EYLEA Q4 (n=498) +8.9 letters, and patients on EYLEA Q8 (n=484) +9.8 letters.

The analyses of these post hoc endpoints were not multiplicity protected and are descriptive only.

  • Early persistent fluid (intraretinal [cystic] or subretinal) was defined as presence of fluid at the first 4 visits (baseline, Week 4, Week 8, and Week 12) after having received 3 initial monthly injections (baseline, Week 4, and Week 8) as seen on TD-OCT7
  • ≈20% of patients with Wet AMD who received EYLEA experienced early persistent retinal fluid7

In this post hoc analysis, patients with early persistent fluid in the EYLEA Q4 group gained 11.7 letters compared
with 7.5 letters in the EYLEA Q8 group

CRT data with EYLEA2-4

Dosing flexibility with
EYLEA in Wet AMD1

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References
  1. EYLEA® (aflibercept) Injection full U.S. Prescribing Information. Regeneron Pharmaceuticals, Inc. March 2021.
  2. Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. lntravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121(1):193-201. doi:10.1016/j.ophtha.2013.08.011
  3. Data on file. Regeneron Pharmaceuticals, Inc.
  4. Heier JS, Brown DM, Chong V, et al; for the VIEW 1 and VIEW 2 Study Groups. lntravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548. doi:10.1016/j.ophtha.2012.09.006
  5. Khurana RN, Rahimy E, Joseph WA, et al. Extended (every 12 weeks or longer) dosing interval with intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration: post hoc analysis of VIEW trials. Am J Ophthalmol. 2019;200:161-168. doi:10.1016/j.ajo.2019.01.005
  6. Kaiser PK, Singer M, Tolentino M, et al. Long-term safety and visual outcome of intravitreal aflibercept in neovascular age-related macular degeneration: VIEW 1 extension study. Ophthalmol Retina. 2017;1(4):304-313. doi:10.1016/j.oret.2017.01.004
  7. Jaffe GJ, Kaiser PK, Thompson D, et al. Differential response to anti-VEGF regimens in age-related macular degeneration patients with early persistent retinal fluid. Ophthalmology. 2016;123(9):1856-1864. doi:10.1016/j.ophtha.2016.05.016