Diabetic Macular Edema (DME) and You Your doctor may have told you that you have DME

This brochure can help you learn about DME and EYLEA® (aflibercept) Injection, a treatment option for DME

For more information, visit www.EYLEA.com. SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION EYLEA® (aflibercept) Injection is a prescription medication administered by injection into the eye. You should not use EYLEA if you have an infection in or around the eye, eye pain or redness, or known allergies to any of the ingredients in EYLEA, including aflibercept. As with all medications, EYLEA can cause side effects.

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. REGEYL068_DME PatientBroch_R2.indd 1

10/29/14 9:26 AM

About DME

[1/National Eye Institute/ Facts About Diabetic Retinopathy/1/A/3/A]

Take action now to help keep your eyes as healthy as possible. DME is a serious eye condition that many people with diabetes face. DME can cause vision problems and even blindness.1

Did you know? [1/National Eye Institute/ Facts About Diabetic Retinopathy/1/A/3/A] [2/ASRS/What Is a Retina Specialist/1/A]

[1/National Eye Institute/ Facts About Diabetic Retinopathy/3/A] [3/ASRS/Diabetic Retinopathy/2/A/3/B]

Your retina specialist is your best resource to help you manage DME.1 He or she is trained to diagnose and treat retina conditions like DME.2 Be sure to get a dilated eye exam at least once a year and follow your retina specialist’s advice.1

To perform a dilated eye exam, your retina specialist first puts drops into your eye to widen (dilate) the opening that controls the flow of light into the eye (the pupil). He or she can then see into the back of the eye (including the retina) for signs of problems.1,3

Understanding diabetes and your eyes In the United States, diabetes affects more than 29 million people.4 Diabetes is the leading cause of blindness in people 20 to 74 years old.5 From 2005 to 2008, in people 40 years or older with diabetes, more than 25% had a serious eye condition (such as DME) that can cause vision loss.4

About DME

DON’T WAIT

[4/CDC/National Diabetes Statistics Report 2014/1/A/6/A] [5/CDC/2011 National Diabetes Fact Sheet/8/A]

People with diabetes are more likely to get certain eye conditions than people without diabetes. These include high pressure in the eye (glaucoma), cloudy lens (cataract), and problems with the light-sensitive tissue in the eye (the retina) that is responsible for vision.6

[6/American Diabetes Association/Eye Complications/1/A–E]

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 2 REGEYL068_DME PatientBroch_R2.indd 2-3

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About DME

UNDERSTANDING DME IS IMPORTANT FOR YOUR EYE HEALTH What is diabetic retinopathy? [1/National Eye Institute/ Facts About Diabetic Retinopathy/1/A] [6/American Diabetes Association/Eye Complications/2/A/3/A]

Diabetic retinopathy—the most common eye condition caused by diabetes—can happen when there is too much sugar (glucose) in the blood.1,6 Too much glucose in the blood damages and blocks the blood vessels in the retina, preventing the retina from getting a supply of blood and nutrients.1 Damaged blood vessels can also leak fluid into the part of the retina responsible for sharp central vision (the macula).1 Blood Vessels

Diabetic retinopathy happens when the blood vessels of the retina become damaged, leaky, and collapsed (closed off).1,6

[6 /American Diabetes Association/Eye Complications/2/B/C/ D/E]

Diabetic retinopathy can lead to DME [1/National Eye Institute/ Facts About Diabetic Retinopathy/2/C]

DME is a complication of diabetic retinopathy. It refers to the swelling of the macula with leaked fluid.1 Macular Edema (white portion) Macula

Macula

Swollen Macula

Normal Macula

Blood Vessels

[1/National Eye Institute/ Facts About Diabetic Retinopathy/1/A]

Leaking Blood Leaking Fluid

Retina

Retina

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 4 REGEYL068_DME PatientBroch_R2.indd 4-5

5 10/29/14 9:26 AM

Symptoms

DME CAN START WITHOUT YOU NOTICING IT

[1/National Eye Institute/ Facts About Diabetic Retinopathy/1/A]

Vision loss or blindness can happen as the macula swells with fluid leaking into the retina, but DME can start even before you notice any symptoms.1

Vision Simulator Card

Symptoms of DME may include1,7

[1/ National Eye Institute/ Facts About Diabetic Retinopathy/2/D/3/F]

Blurriness in the center of vision

Blind spots or patches

Symptoms

Share the enclosed card with your loved one so he or she can see how DME might affect your vision.

[7/AAO EyeSmart/ Macular Edema Symptoms/1/A/B]

Did you know? If you have diabetes, you should get a dilated eye exam from a retina specialist at least once a year.1

Waviness in the center of vision

Colors that look dull

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 6 REGEYL068_DME PatientBroch_R2.indd 6-7

CLIENT NOTE: Printer to confirm construction.

[1/National Eye Institute/ Facts About Diabetic Retinopathy/2/B/3/E]

Early diagnosis and treatment are important If not treated, DME can cause vision problems and even vision loss.1

[1/National Eye Institute/ Facts About Diabetic Retinopathy1/A/2/B/3/ C/E]

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Diagnosis

HOW YOUR DOCTOR DIAGNOSES DME

[1/National Eye Institute/ Facts About Diabetic Retinopathy/3/A/E] [3/ASRS/Diabetic Retinopathy/2/A/3/A/B]

Your retina specialist has different tests for diagnosing DME.1,3 Some commonly used tests are listed below. Dilated eye exam1,3 Your retina specialist puts drops into your eye to dilate the pupil. He or she can then see into the back of the eye (including the retina) for signs of problems.

[1/National Eye Institute/ Facts About Diabetic Retinopathy/3/A] [3/ASRS/Diabetic Retinopathy/2/A/3/B]

Fundus photography3 Shows the inside of the back of the eye.

[3/ASRS/Diabetic Retinopathy/3/A]

[1/National Eye Institute/ Facts About Diabetic Retinopathy/3/A] [3/ASRS/Diabetic Retinopathy/3/A]

Optical coherence tomography1,3 Shows the layers and thickness of the retina.

[1/National Eye Institute/ Facts About Diabetic Retinopathy/3/A] [3/ASRS/Diabetic Retinopathy/3/A]

Visual acuity test1,8 Measures how well you see the letters on an eye chart from a distance.

[1/National Eye Institute/ Facts About Diabetic Retinopathy/3/A] [8/American Optometric Association/What Is 20/20 Vision/1/A]

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 8 REGEYL068_DME PatientBroch_R2.indd 8-9

Diagnosis

Fluorescein angiography1,3 Dye is used to show the blood vessels in the back of the eye.

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About EYLEA

EYLEA has been approved by the Food and Drug Administration for the treatment of DME. EYLEA is a prescription medication, given by injection into the eye, that works by blocking vascular endothelial growth factor (anti-VEGF treatment). EYLEA in the eye EYLEA VEGF trapped by arms of EYLEA

About EYLEA

TREATMENT WITH EYLEA® (aflibercept) INJECTION

VEGF

What is VEGF? Some people with diabetes have high levels of VEGF, a type of protein made by the blood vessels. At high levels, VEGF can cause fluid to leak into the macula. DME happens as the macula swells with the fluid. Blocking VEGF helps reduce fluid from leaking into the macula.9

[9/AAO EyeSmart/ Macular Edema Treatment/1/A]

SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION Injection into the eye can result in an infection in the eye and retinal detachment. Inflammation in the eye has been reported with the use of EYLEA.

Blood vessel

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 10 REGEYL068_DME PatientBroch_R2.indd 10-11

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About EYLEA [EYLEA PI/6/A/7/B/C]

VISION IMPROVEMENT IN DME

EYLEA® (aflibercept) Injection was researched in 2 clinical studies of 862 people with DME who were given EYLEA once every 8 weeks (after 5 initial monthly doses) or once every 4 weeks, or instead, were treated with laser (control). Both studies measured the number of letters on the eye chart people saw at 1 year compared to the number of letters they saw when the study started. DME Study 1: Results at Year 1

10.7

15 10

more letters than when the study started (n=151)

12.5

more letters than when the study started

more letters than when the study started (n=154)

EYLEA dosed EYLEA dosed Control every 8 weeks every 4 weeks (after 5 initial monthly doses) These results are from 2 clinical studies; your individual results may vary.

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 12 REGEYL068_DME PatientBroch_R2.indd 12-13

15

10.7

10.5

(n=135)

(n=136)

more letters more letters than when than when the study started the study started

1.2

more letters than when the study started

5

0.2

0

DME Study 2: Results at Year 1

10

(n=154)

5

On average, at the end of year 1 in both studies: • People treated with EYLEA® (aflibercept) Injection saw 10 more letters on the eye chart than when each study started • The number of letters gained by patients treated with EYLEA was much greater than control

(n=132)

0

EYLEA dosed every 8 weeks (after 5 initial monthly doses)

EYLEA dosed every 4 weeks

Control

SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION In some patients, injections with EYLEA may trigger a temporary increase in eye pressure within 1 hour of the injection. 13 10/29/14 9:26 AM

About EYLEA

VISION IMPROVEMENT IN DME

[EYLEA PI/6/A/7/B/C]

In the 2 clinical studies, people treated with EYLEA® (aflibercept) Injection could see, on average, more letters on the eye chart at 1 year than when each study started. On average, patients beginning these studies could see this much on the eye chart: 20/20010: Severe Low Vision11 • Legal blindness in the United States10

[10/American Optometric Association/1/A] [11/Colenbrander/9/A]

More than a third of people treated with EYLEA® (aflibercept) Injection improved by at least 15 letters (3 lines) on the eye chart at 1 year.

[EYLEA PI/6/A/7/B/C]

On average, patients receiving EYLEA could see this much on the eye chart at the end of 1 year:

[EYLEA PI/6/A/7/B/C]

20/160–20/8011: Moderate Low Vision11 • Reading with aids and magnifiers11 20/4012: Near-Normal Vision11 • Often a minimum requirement for driving a vehicle11

[12/Boyer/156/A/161/A] [11/Colenbrander/9/A]

These results are from 2 clinical studies; your individual results may vary.

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 14 REGEYL068_DME PatientBroch_R2.indd 14-15

SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION Sustained increases in eye pressure have been reported with repeated injections, and your doctor may monitor this after each injection. 15 10/29/14 9:26 AM

About EYLEA

DOSING AND POSSIBLE SIDE EFFECTS [EYLEA PI/2/A]

Dosing for DME • E  YLEA® (aflibercept) Injection is a prescription medicine approved for the treatment of patients with Diabetic Macular Edema. • The recommended dose for EYLEA is 2-mg administered by injection in the eye every 2 months (8 weeks) following 5 initial monthly (4 weeks) injections. • EYLEA may be dosed once per month, but additional benefit was not seen with this dosing plan. Your retina specialist will decide what EYLEA dosing schedule is right for you.

[EYLEA PI/4/A/D/5/A]

EYLEA has been studied for safety and efficacy in more than 3,000 people with DME and other FDA-approved eye conditions EYLEA was also studied in adults of various ages and in some adults with kidney disease, with no changes in dosing needed.

Possible Side Effects • Injection into the eye can result in an infection in the eye and retinal detachment. Inflammation in the eye has been reported with the use of EYLEA® (aflibercept) Injection. • In some patients, injections with EYLEA may trigger a temporary increase in eye pressure within 1 hour of the injection. Sustained increases in eye pressure have been reported with repeated injections, and your doctor may monitor this after each injection. • T  here is a potential risk of serious and sometimes fatal side effects related to blood clots, leading to heart attack or stroke in patients receiving EYLEA. • T  he most common side effects reported in patients receiving EYLEA are increased redness in the eye, eye pain, cataract, moving spots in the field of vision, increased pressure in the eye, and vitreous (gel-like substance) detachment. • S  erious side effects related to the injection procedure are rare but can occur including infection inside the eye, retinal detachment, cataract, increased pressure in the eye, and vitreous detachment.

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 16 REGEYL068_DME PatientBroch_R2.indd 16-17

17 10/29/14 9:26 AM

Safety Information

IMPORTANT SAFETY INFORMATION

Safety Information

IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION • E  YLEA® (aflibercept) Injection is a prescription medication administered by injection into the eye. You should not use EYLEA if you have an infection in or around the eye, eye pain or redness, or known allergies to any of the ingredients in EYLEA, including aflibercept. As with all medications, EYLEA can cause side effects. • Injection into the eye can result in an infection in the eye and retinal detachment. Inflammation in the eye has been reported with the use of EYLEA. • In some patients, injections with EYLEA may trigger a temporary increase in eye pressure within 1 hour of the injection. •S  ustained increases in eye pressure have been reported with repeated injections, and your doctor may monitor this after each injection. • T  here is a potential risk of serious and sometimes fatal side effects related to blood clots, leading to heart attack or stroke in patients receiving EYLEA.

• T  he most common side effects reported in patients receiving EYLEA® (aflibercept) Injection are increased redness in the eye, eye pain, cataract, moving spots in the field of vision, increased pressure in the eye, and vitreous (gel-like substance) detachment. • S  erious side effects related to the injection procedure are rare but can occur including infection inside the eye, retinal detachment, cataract, increased pressure in the eye, and vitreous detachment. • It is important that you contact your doctor right away if you think you might be experiencing any side effects. • E  YLEA is for prescription use only. For additional safety information, please talk to your doctor and see the full Prescribing Information for EYLEA. • Y  ou are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see enclosed full Prescribing Information. 18 REGEYL068_DME PatientBroch_R2.indd 18-19

19 10/29/14 9:26 AM

What to Expect

PREPARING FOR YOUR INJECTION

Before your appointment • Arrange for someone to drive you to and from the appointment •A  sk your retina specialist’s office how long the appointment might be so you will be prepared •B  ring with you —A list of any questions you have (don’t be afraid to ask them) —A list of all prescription and over-thecounter medicines you take and how often you take them —Dark glasses (your eyes may be sensitive to light afterwards)

• Y  ou may have a temporary increase in eye pressure. Your retina specialist will have checked you for this • Your eyes may be sensitive to light Did you know? You may be eligible for transportation to your appointment through Rides in Sight, a transportation-referral service. Call 1-855-607-4337 or visit www.ridesinsight.org. SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION Injection into the eye can result in an infection in the eye and retinal detachment. Inflammation in the eye has been reported with the use of EYLEA.

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 20 REGEYL068_DME PatientBroch_R2.indd 20-21

[EYLEA PI/7/E]

What to Expect

During your appointment • Your retina specialist will —Examine your eye and discuss the procedure with you —Wash and numb your eye —Check your eye pressure after the injection

After your appointment • You may have some visual problems that are temporary. Do not drive or operate machinery if you have these symptoms

21 10/29/14 9:26 AM

About EYLEA4U

Program

If you

Your EYLEA4U® Support Specialist can provide support and information on EYLEA® (aflibercept) Injection for treatment of DME

Patient Assistance Program

Lack insurance coverage for EYLEA or are uninsured

Get in touch with an EYLEA4U Support Specialist today.

EYLEA Co-Pay Card Program

Have commercial insurance (not funded through a government healthcare program)

EYLEA4U® has 3 programs that may be able to help you, if you qualify, with the cost of EYLEA treatment.

Independent Co-Pay Assistance Foundations

Are insured through a government healthcare program (such as Medicare or Medicare Advantage)

Help With Cost

NEED HELP WITH THE COST OF EYLEA® (aflibercept) INJECTION?

Call 1-855-EYLEA4U (1-855-395-3248) and press Option 4, Monday through Friday, 9 am to 8 pm Eastern Time.

SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION There is a potential risk of serious and sometimes fatal side effects related to blood clots, leading to heart attack or stroke in patients receiving EYLEA.

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 22 REGEYL068_DME PatientBroch_R2.indd 22-23

23 10/29/14 9:26 AM

FAQs

QUESTIONS TO ASK YOUR DOCTOR

Bring a list of questions, and don’t be afraid to ask them.

Questions you might ask include • How might DME continue to affect my vision? •W  hat are the side effects of the treatment? • How often do I need to get the treatment?

• Is the treatment working?

FAQs

•H  ow long will I continue to be on treatment for DME? • Is there anything else I can do to improve my condition?

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 24 REGEYL068_DME PatientBroch_R2.indd 24-25

25 10/29/14 9:26 AM

Living With DME

THERE ARE THINGS YOU CAN DO

In addition to treatment, what else can I do? [1/National Eye Institute/ Facts About Diabetic Retinopathy/3/B/D/5/A] [6/American Diabetes Association/Eye Complications/3/A] [13/CDC/Prevent Diabetes] [1/National Eye Institute/ Facts About Diabetic Retinopathy/3/B/D/5/A]

• C  ontrol blood sugar and blood pressure through diet and exercise1,6,13 • Take your blood pressure and diabetes medications as prescribed1,6,13 •L  ow vision specialists and vision aids can help if you need to make lifestyle changes because of low vision1 Did you know?

[5/CDC/2011 National Diabetes Fact Sheet/8/A]

[14/Lighthouse International/The Amsler Grid/1/A]

Routinely checking your vision at home is also important.14 You can use the enclosed Amsler grid on page 27 as a tool to help check your vision.

What is a low vision specialist? This is a professional who can provide advice and guidance on any lifestyle changes you need to make because of low vision. Ask your retina specialist if meeting with a low vision specialist would be right for you.1 What are vision aids? Vision aids can help many people with low vision perform everyday tasks. Vision aids include15 Magnifying glasses

Sound alerts on smartphones

Special computer screens with bigger type sizes

Better lighting (less glare, more contrast)

Report any changes in your vision to your retina specialist right away.1

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. 26 REGEYL068_DME PatientBroch_R2.indd 26-27

[1/National Eye Institute/ Facts About Diabetic Retinopathy/5/A]

[15/AAO EyeSmart/Low Vision Aids/1/A/B/2/A]

Living With DME

[1/National Eye Institute/ Facts About Diabetic Retinopathy/1/A]

Diabetes is the leading cause of vision loss among working-age people in the United States.5

Pull out the Amsler grid to help check your vision

27 10/29/14 9:26 AM

Living With DME: Regeneron Is Here to Help! Find more information and support at www.EYLEA.com

References: 1. Facts about diabetic retinopathy. National Institutes of Health, National Eye Institute Web site. http://www.nei.nih.gov/health/diabetic/retinopathy.asp. Accessed August 8, 2014. 2. What is a retina specialist? American Society of Retina Specialists Web site. http://www.asrs.org/patients/what-is-a-retina-specialist. Accessed August 8, 2014. 3. Diabetic retinopathy. American Society of Retina Specialists Web site. http://www.asrs.org/patients/ retinal-diseases/3/diabetic-retinopathy. Accessed August 8, 2014. 4. National Diabetes Statistics Report, 2014. Centers for Disease Control and Prevention Web site. http://www.cdc. gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Accessed August 8, 2014. 5. 2011 National Diabetes Fact Sheet. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed August 8, 2014. 6. Eye complications. American Diabetes Association Web site. http://www.diabetes.org/ living-with-diabetes/complications/eye-complications/. Accessed August 8, 2014. 7. Macular edema symptoms. American Academy of Ophthalmology (AAO EyeSmart) Web site. http://www.geteyesmart.org/eyesmart/diseases/macular-edema-symptoms.cfm. Accessed August 8, 2014. 8. Visual acuity: what is 20/20 vision? American Optometric Association Web site. http://www.aoa.org/patients-and-public/eye-and-vision-problems/glossary-of-eye-and-visionconditions/visual-acuity?sso=y. Accessed August 8, 2014. 9. Macular edema treatment. American Academy of Ophthalmology (AAO EyeSmart) Web site. http://www.geteyesmart.org/ eyesmart/diseases/macular-edema-treatment.cfm. Accessed August 8, 2014. 10. Low vision. American Optometric Association Web site. http://www.aoa.org/patients-and-public/caring-foryour-vision/low-vision?sso=y. Accessed August 26, 2014. 11. Colenbrander A. Measuring vision and vision loss. In: Tasman W, Jaeger EA, eds. Duane’s Ophthalmology. 2006 ed. Philadelphia, PA: Lippincott Williams & Wilkins. http://www.oculist.net/downaton502/prof/ebook/duanes/pages/ v5/v5c051.html#t7. Accessed August 26, 2014. 12. Boyer DS, Hopkins JJ, Sorof J, Ehrlich JS. Anti-vascular endothelial growth factor therapy for diabetic macular edema. Ther Adv Endocrinol Metab. 2013;4(6):151-169. 13. Prevent diabetes. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/diabetes/consumer/prevent.htm. Accessed August 8, 2014. 14. The Amsler grid. Lighthouse International Web site. http://lighthouse.org/about-low-visionblindness/amsler-grid/. Accessed August 8, 2014. 15. Low vision aids and low vision rehabilitation. American Academy of Ophthalmology (AAO EyeSmart) Web site. http://www. geteyesmart.org/eyesmart/diseases/low-vision-aids-rehabilitation.cfm. Accessed August 8, 2014.

Please see Important Safety Information on pages 18-19 and enclosed full Prescribing Information. EYLEA and EYLEA4U are registered trademarks of Regeneron Pharmaceuticals, Inc.

©2014, Regeneron Pharmaceuticals, Inc.,  777 Old Saw Mill River Road, Tarrytown, NY 10591 

REGEYL068_DME PatientBroch_R2.indd 28

All rights reserved 

09/2014 LEA-0309A

10/29/14 9:26 AM

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use EYLEA safely and effectively. See full prescribing information for EYLEA. EYLEA® (aflibercept) Injection For Intravitreal Injection Initial U.S. Approval: 2011

RECENT MAJOR CHANGES

• Indications and Usage, Macular Edema Following Retinal Vein Occlusion (RVO) (1.2) • Indications and Usage, Diabetic Macular Edema (DME) (1.3) • Dosage and Administration, Macular Edema Following Retinal Vein Occlusion (RVO) (2.3) • Dosage and Administration, Diabetic Macular Edema (DME) (2.4) • Dosage and Administration, Preparation for Administration (2.5) • Warnings and Precautions, Thromboembolic Events (5.3)

INDICATIONS AND USAGE

40 mg/mL solution for intravitreal injection in a single-use vial (3)

10/2014 7/2014 1/2014 10/2014

• Ocular or periocular infection (4.1) • Active intraocular inflammation (4.2) • Hypersensitivity (4.3)

DOSAGE AND ADMINISTRATION

Neovascular (Wet) Age-Related Macular Degeneration (AMD) • The recommended dose for EYLEA is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (monthly) for the first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). (2.2) • Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks. (2.2) Macular Edema Following Retinal Vein Occlusion (RVO) • The recommended dose for EYLEA is 2 mg (0.05 mL) administered by intravitreal injection once every 4 weeks (monthly). (2.3)

FULL PRESCRIBING INFORMATION: CONTENTS* 1

INDICATIONS AND USAGE 1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD) 1.2 Macular Edema Following Retinal Vein Occlusion (RVO) 1.3 Diabetic Macular Edema (DME)

2

DOSAGE AND ADMINISTRATION 2.1 Important Injection Instructions 2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD) 2.3 Macular Edema Following Retinal Vein Occlusion (RVO) 2.4 Diabetic Macular Edema (DME) 2.5 Preparation for Administration 2.6 Injection Procedure

3

DOSAGE FORMS AND STRENGTHS

5

WARNINGS AND PRECAUTIONS 5.1 Endophthalmitis and Retinal Detachments 5.2 Increase in Intraocular Pressure 5.3 Thromboembolic Events

6

ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Immunogenicity

DOSAGE FORMS AND STRENGTHS

10/2014 7/2014

EYLEA is indicated for the treatment of patients with: • Neovascular (Wet) Age-Related Macular Degeneration (AMD) (1.1) • Macular Edema Following Retinal Vein Occlusion (RVO) (1.2) • Diabetic Macular Edema (DME) (1.3)

4 CONTRAINDICATIONS 4.1 Ocular or Periocular Infections 4.2 Active Intraocular Inflammation 4.3 Hypersensitivity

Diabetic Macular Edema (DME) • The recommended dose for EYLEA is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (monthly) for the first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). (2.4) • Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks. (2.4)

CONTRAINDICATIONS



WARNINGS AND PRECAUTIONS



ADVERSE REACTIONS

• Endophthalmitis and retinal detachments may occur following intravitreal injections. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. (5.1) • Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. (5.2) • There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors. (5.3) The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous floaters, intraocular pressure increased, and vitreous detachment. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-855-395-3248 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION

8

Revised: 10/2014

USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use

11 DESCRIPTION 12

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics

13

NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology

14

CLINICAL STUDIES 14.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD) 14.2 Macular Edema Following Central Retinal Vein Occlusion (CRVO) 14.3 Macular Edema Following Branch Retinal Vein Occlusion (BRVO) 14.4 Diabetic Macular Edema (DME)

16

HOW SUPPLIED/STORAGE AND HANDLING

17

PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are not listed

0.7 0.8

0.5 0.6

0.3 0.4

0.1 0.2 0.9 1m l

0.7 0.8

0.5 0.6

0.3 0.4

7. Remove the filter needle from the syringe and properly dispose of the filter needle. Note: Filter needle is not to be used for intravitreal injection. 8. Remove the 30-gauge x ½-inch injection needle from the plastic pouch and attach the injection needle to the syringe by firmly twisting the injection needle onto the Luer lock syringe tip (see Figure 5). Figure 5:

0.1 02 0.

1. Remove the protective plastic cap from the vial (see Figure 1). Figure 1:

6. Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to completely empty the filter needle.

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The glass vial is for single use only.

Needle Bevel Pointing Down Solution

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Using aseptic technique, the intravitreal injection should be performed with a 30-gauge x ½-inch injection needle. Vial

5. Using aseptic technique withdraw all of the EYLEA vial contents into the syringe, keeping the vial in an upright position, slightly inclined to ease complete withdrawal. To deter the introduction of air, ensure the bevel of the filter needle is submerged into the liquid. Continue to tilt the vial during withdrawal keeping the bevel of the filter needle submerged in the liquid (see Figures 4a and 4b). Figure 4a: Figure 4b:

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1 INDICATIONS AND USAGE EYLEA is indicated for the treatment of patients with: 1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD) 1.2 Macular Edema Following Retinal Vein Occlusion (RVO) 1.3 Diabetic Macular Edema (DME) 2 DOSAGE AND ADMINISTRATION 2.1 Important Injection Instructions For ophthalmic intravitreal injection. EYLEA must only be administered by a qualified physician. 2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD) The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (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 (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks [see Clinical Studies (14.1)]. 2.3 Macular Edema Following Retinal Vein Occlusion (RVO) The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection once every 4 weeks (monthly) [see Clinical Studies (14.2), (14.3)]. 2.4 Diabetic Macular Edema (DME) The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (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 (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks [see Clinical Studies (14.4)]. 2.5 Preparation for Administration EYLEA should be inspected visually prior to administration. If particulates, cloudiness, or discoloration are visible, the vial must not be used.

4. Push the filter needle into the center of the vial stopper until the needle is completely inserted into the vial and the tip touches the bottom or bottom edge of the vial.

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FULL PRESCRIBING INFORMATION

9. When ready to administer EYLEA, remove the plastic needle shield from the needle. 10. Holding the syringe with the needle pointing up, check the syringe for bubbles. If there are bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure 6). Figure 6:

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2. Clean the top of the vial with an alcohol wipe (see Figure 2). Figure 2:

11. To eliminate all of the bubbles and to expel excess drug, SLOWLY depress the plunger so that the plunger tip aligns with the line that marks 0.05 mL on the syringe (see Figures 7a and 7b). Figure 7a:

Figure 7b: Solution after expelling air bubbles and excess drug Dosing Line for 0.05 ml

3. Remove the 19-gauge x 1½-inch, 5-micron, filter needle from its pouch and remove the 1‑mL syringe supplied in the carton from its pouch. Attach the filter needle to the syringe by twisting it onto the Luer lock syringe tip (see Figure 3). Figure 3:

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Flat Plunger Edge

2.6 Injection Procedure The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include surgical hand disinfection and the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a topical broad–spectrum microbicide should be given prior to the injection.

l 1m

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Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, a sterile paracentesis needle should be available.

Following intravitreal injection, patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., eye pain, redness of the eye, photophobia, blurring of vision) without delay [see Patient Counseling Information (17)]. Each vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before EYLEA is administered to the other eye. After injection, any unused product must be discarded. 3 DOSAGE FORMS AND STRENGTHS Single-use, glass vial designed to provide 0.05 mL of 40 mg/mL solution (2 mg) for intravitreal injection. 4 CONTRAINDICATIONS 4.1 Ocular or Periocular Infections EYLEA is contraindicated in patients with ocular or periocular infections. 4.2 Active Intraocular Inflammation EYLEA is contraindicated in patients with active intraocular inflammation. 4.3 Hypersensitivity EYLEA is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in EYLEA. Hypersensitivity reactions may manifest as severe intraocular inflammation. 5 WARNINGS AND PRECAUTIONS 5.1 Endophthalmitis and Retinal Detachments Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1)]. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately [see Dosage and Administration (2.6) and Patient Counseling Information (17)]. 5.2 Increase in Intraocular Pressure Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA [see Adverse Reactions (6.1)]. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with vascular endothelial growth factor (VEGF) inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately [see Dosage and Administration (2.6)]. 5.3 Thromboembolic Events There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA. The incidence in the DME studies during the first year was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies. 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in the Warnings and Precautions (5) section of the labeling: •

Endophthalmitis and retinal detachments

•

Increased intraocular pressure

• Thromboembolic events 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice. A total of 2711 patients treated with EYLEA constituted the safety population in seven phase 3 studies. Among those, 2110 patients were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in