EYLEA® (aflibercept) Submitted for EU Marketing Authorization for the Treatment of Macular Edema Following Central Retinal Vein Occlusion

TARRYTOWN, N.Y. and BERLIN, Dec. 6, 2012 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Bayer HealthCare today announced that Bayer HealthCare has submitted an application for marketing authorization in Europe for EYLEA (aflibercept) Injection for the treatment of macular edema following Central Retinal Vein Occlusion (CRVO).

"It is our pleasure to announce the filing for EYLEA for the macular edema following CRVO indication with the European Regulatory Authority (EMA) immediately after receiving approval for the treatment of wet age-related macular degeneration.  We hope this will extend the benefits of EYLEA as a new treatment option to European patients with macular edema secondary to central retinal vein occlusion," said Kemal Malik, M.D., Head of Global Development and member of the Bayer HealthCare Executive Committee.  "With 52 weeks results of two Phase 3 trials showing substantial and sustained improvement in vision relative to the sham control group, EYLEA has the potential to provide patients and physicians a new treatment option for central retinal vein occlusion."

The submission of EYLEA for Macular Edema following CRVO is based on data from the Phase 3 COPERNICUS and GALILEO studies.  In both studies, the primary efficacy endpoint was the proportion of patients who gained at least 15 ETDRS letters of Best Corrected Visual Acuity (BCVA) at 24 weeks compared to baseline on the ETDRS visual acuity charts.  The EYLEA 2 milligrams (mg) monthly group was significantly superior to the sham control group for the primary endpoint.  The effects were largely maintained until week 52. 

EYLEA is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA. 

EYLEA was approved in the United States for the treatment of wet AMD in November 2011 and for macular edema following CRVO in September 2012.  EYLEA was also approved in Europe, Japan, Australia, and in several other countries earlier this year for use in wet AMD.

Phase 3 trials are currently under way with EYLEA in the treatment of diabetic macular edema (DME), branch retinal vein occlusion (BRVO), and myopic choroidal neovascularization (mCNV).

Bayer HealthCare and Regeneron are collaborating on the global development of EYLEA.  Regeneron maintains exclusive rights to EYLEA in the United States.  Bayer HealthCare licensed the exclusive marketing rights outside the United States, where the companies will share equally the profits from any future sales of EYLEA.

About EYLEA^® (aflibercept) Injection For Intravitreal Injection
Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body.  Its normal role in a healthy organism is to trigger formation of new blood vessels (angiogenesis) supporting the growth of the body's tissues and organs.  However, in certain diseases, such as wet age-related macular degeneration, it is also associated with the growth of abnormal new blood vessels in the eye, which exhibit abnormal increased permeability that leads to edema.  Scarring and loss of fine-resolution central vision often results.  In Central Retinal Vein Occlusion (CRVO), a blockage occurs in the main blood vessel that transports deoxygenated blood away from the retina.  VEGF levels are elevated in response contributing to macular edema.

EYLEA 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 and formulated as an iso-osmotic solution for intravitreal administration.  EYLEA acts as a soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of these cognate VEGF receptors.  EYLEA is specially purified and contains iso-osmotic buffer concentrations, allowing for injection into the eye.

In the United States, EYLEA is approved for the treatment of wet AMD and Macular Edema following CRVO.  Phase 3 trials are currently underway with EYLEA for the treatment of diabetic macular edema (DME) and Macular Edema following Branch Retinal Vein Occlusion (BRVO). 

IMPORTANT U.S. PRESCRIBING INFORMATION FOR EYLEA^® (aflibercept) INJECTION
In the United States, EYLEA^® (aflibercept) Injection is indicated for the treatment of patients with neovascular (Wet) Age-related Macular Degeneration (AMD).  The recommended dose for EYLEA is 2 mg administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg 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.

In the United States, EYLEA is also indicated for the treatment of patients with Macular Edema following Central Retinal Vein Occlusion (CRVO).  The recommended dose for EYLEA is 2 mg administered by intravitreal injection every 4 weeks (monthly).

IMPORTANT SAFETY INFORMATION FOR EYLEA^® (aflibercept) INJECTION
EYLEA^® (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA.

Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments.  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. Intraocular inflammation has been reported during the post approval use of EYLEA.

Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA.  Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors.  Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.

There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including EYLEA, defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).  The incidence of ATEs in the VIEW 1 and VIEW 2 wet AMD studies in patients treated with EYLEA was 1.8% during the first year. The incidence of ATEs in the COPERNICUS and GALILEO CRVO studies was 0% in patients treated with EYLEA compared with 1.4% in patients receiving sham control during the first six months.

The most common adverse reactions (5% or more) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.

Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections with EYLEA including endophthalmitis, traumatic cataract, increased intraocular pressure, and vitreous detachment.

Please see the full Prescribing Information at www.EYLEA.com.

About Central Retinal Vein Occlusion (CRVO)
Over 100,000 people in the United States and more than 66,000 people in major European countries are estimated to suffer from CRVO. CRVO is caused by obstruction of the central retinal vein that leads to a back up of blood and fluid in the retina.  The fluid can result in retinal injury and loss of vision.  VEGF levels are elevated in response to this retinal injury contributing to macular edema.  It is believed that anti-VEGF treatment may help decrease vascular permeability and edema.

About Regeneron Pharmaceuticals
Regeneron is a fully integrated biopharmaceutical company that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions.  Regeneron markets three products in the United States, EYLEA^® (aflibercept) Injection, ZALTRAP^® (ziv-aflibercept) Injection for Intravenous Infusion, and ARCALYST^® (rilonacept) Injection for Subcutaneous Use, ZALTRAP is co-commercialized with Sanofi. Phase 3 studies are in progress with EYLEA in two additional indications and with product candidates, sarilumab and REGN727.  Regeneron has active research and development programs in many disease areas, including ophthalmology, inflammation, cancer, and hypercholesterolemia.  Additional information and recent news releases are available on the Regeneron web site at www.regeneron.com.

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials.  Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 17.2 billion (2011), is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany.  The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions.  Bayer HealthCare's aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide.  Bayer HealthCare has a global workforce of 55,700 employees (Dec 31, 2011) and is represented in more than 100 countries.  More information at www.healthcare.bayer.com. 

Regeneron Forward Looking-Statement
This news release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron, and actual events or results may differ materially from these forward-looking statements.  These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates and research and clinical programs now underway or planned, including without limitation EYLEA, unforeseen safety issues resulting from the administration of products and product candidates in patients, the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates, determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and drug candidates, competing drugs that may be superior to Regeneron's products and drug candidates, uncertainty of market acceptance of Regeneron's products and drug candidates, unanticipated expenses, the costs of developing, producing, and selling products, the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare, to be canceled or terminated, and risks associated with third party intellectual property and pending or future litigation relating thereto.  A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2011 and its Form 10-Q for the quarter ended September 30, 2012.  Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events, or otherwise, unless required by law.

Bayer Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

SOURCE Regeneron Pharmaceuticals