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Press release from PR Newswire

Regeneron Submits Biologics License Application to FDA for VEGF Trap-Eye for Treatment of Wet Age-Related Macular Degeneration

Tuesday, February 22, 2011

Regeneron Submits Biologics License Application to FDA for VEGF Trap-Eye for Treatment of Wet Age-Related Macular Degeneration08:00 EST Tuesday, February 22, 2011TARRYTOWN, N.Y., Feb. 22, 2011 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) today announced that the company submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for VEGF Trap-Eye for the treatment of the neovascular form of age-related macular degeneration (wet AMD).  Under the Prescription Drug User Fee Act (PDUFA), the goal for a standard review time from submission to FDA action is ten months.  Regeneron's submission includes a request for Priority Review, which, if granted, would shorten the FDA's targeted goal for review time under PDUFA to six months. "There have been significant advances in the treatment of wet AMD in recent years.  However, the need for monthly intravitreal injections to obtain optimal vision gains has resulted in a significant burden for physicians, patients, and their caregivers," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron.  "We are extremely proud to have conducted the largest global Phase 3 clinical program in patients with wet AMD, which demonstrated that patients treated with VEGF Trap-Eye 2 mg every two months, following three loading doses, were able to be dosed with fewer injections over one year without compromising efficacy.  We look forward to working closely with the FDA to bring this potentially important new medicine to patients with wet AMD."  The VEGF Trap-Eye BLA is based on the positive results from two Phase 3 trials, the North American VIEW 1 trial and the global VIEW 2 trial.  In these trials, all regimens of VEGF Trap-Eye, including VEGF Trap-Eye dosed 2 milligrams (mg) every two months (following three loading doses), successfully met the primary endpoint of non-inferiority, compared to the current standard of care, ranibizumab 0.5 mg dosed every month.  The primary endpoint analysis was statistical non-inferiority in the proportion of patients who maintained (or improved) vision over 52 weeks compared to ranibizumab.  A generally favorable safety profile was observed for both VEGF Trap-Eye and ranibizumab.  The ocular adverse events were balanced across all treatment groups in both studies.  There were no notable differences in non-ocular adverse events among the study arms. About the VIEW Program The VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) program consists of two randomized, double-masked, Phase 3 clinical trials evaluating VEGF Trap-Eye in the treatment of the neovascular form of age-related macular degeneration (wet AMD).  The VIEW 1 study, which randomized 1217 patients, is being conducted in the United States and Canada by Regeneron under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration.  The VIEW 2 study, which randomized 1240 patients, is being conducted in Europe, Asia Pacific, Japan, and Latin America by Bayer HealthCare.  The study designs are essentially identical.  The primary endpoint evaluation was conducted at 52 weeks. In each of the studies, VEGF Trap-Eye was evaluated for its effect on maintaining and improving vision when dosed as an intravitreal injection on a schedule of 0.5 mg monthly, 2.0 mg monthly, or 2.0 mg every two months (following three monthly loading doses), as compared with intravitreal ranibizumab administered 0.5 mg every month during the first year of the studies.  The primary endpoint of these non-inferiority studies was the proportion of patients treated with VEGF Trap-Eye who maintained visual acuity at the end of one year, compared to ranibizumab patients.  Visual acuity was measured as a score based on the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart, a standard chart used in research to measure visual acuity.  Maintenance of vision was defined as losing fewer than three lines (equivalent to 15 letters) on the ETDRS eye chart. The following table summarizes the VIEW 1 and VIEW 2 results for the primary and the first secondary endpoint pre-specified for testing:Ranibizumab0.5mg monthlyVEGF Trap-Eye0.5mg monthlyVEGF Trap-Eye2mg monthlyVEGF Trap-Eye2mg every 2months Maintenance of vision* (% patients losing <15 letters) at week 52 versus baseline VIEW 1 94.4%95.9%**95.1%**95.1%**VIEW 294.4%96.3%**95.6%**95.6%**Mean improvement in vision* (letters) at 52 weeks versus baseline (p-value versus ranibizumab 0.5mg monthly)***VIEW 1 8.16.9 (NS)10.9 (p<0.01)7.9 (NS)VIEW 2 9.49.7 (NS)  7.6 (NS)8.9 (NS)*Visual acuity was measured as the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart**Statistically non-inferior based on a non-inferiority margin of 10%, using confidence interval approach (95.1% and 95% for VIEW 1 and VIEW 2, respectively)*** Test for superiorityNS=not statistically significantIn the VIEW 1 and VIEW 2 trials, a generally favorable safety profile was observed for both VEGF Trap-Eye and ranibizumab. The incidence of ocular treatment emergent adverse events was balanced across all four treatment groups in both studies, with the most frequent events associated with the injection procedure, the underlying disease, and/or the aging process.  The most frequent ocular adverse events were conjunctival hemorrhage, macular degeneration, eye pain, retinal hemorrhage, and vitreous floaters.  The most frequent serious non-ocular adverse events were typical of those reported in this elderly population who receive intravitreal treatment for wet AMD; the most frequently reported events were falls, pneumonia, myocardial infarction, atrial fibrillation, breast cancer, and acute coronary syndrome.  There were no notable differences among the study arms.As-needed (PRN) dosing with both agents, with a dose administered at least every three months (but not more often than monthly), is being evaluated during the second year of VIEW 1 and VIEW 2.  These studies are part of the global development program for VEGF Trap-Eye being conducted by Regeneron and Bayer HealthCare.About VEGF Trap-EyeVEGF Trap-Eye is a fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 that binds all forms of VEGF-A, along with the related Placental Growth Factor (PlGF).  VEGF Trap-Eye is a specific and highly potent blocker of these growth factors.  VEGF Trap-Eye is specially purified and contains iso-osmotic buffer concentrations, allowing for injection into the eye.Regeneron and Bayer HealthCare are collaborating on the development of VEGF Trap-Eye for the treatment of wet AMD, central retinal vein occlusion, diabetic macular edema, myopic choroidal neovascularisation, and other eye diseases and disorders.  Bayer HealthCare intends to submit regulatory applications in the first half of 2011 for marketing approval in Europe.  If approved by regulatory authorities, Bayer HealthCare will market VEGF Trap-Eye outside the United States, where the companies will share equally in profits from any future sales of VEGF Trap-Eye.  Regeneron maintains exclusive rights to VEGF Trap-Eye in the United States.About Wet Age-Related Macular Degeneration (wet AMD)Age-related macular degeneration (AMD) is a leading cause of acquired blindness.  Macular degeneration is diagnosed as either dry (non-exudative) or wet (exudative).  In wet AMD, new blood vessels grow beneath the retina and leak blood and fluid.  This leakage causes disruption and dysfunction of the retina creating distortion and/or blind spots in central vision, and it can account for blindness in wet AMD patients.  Wet AMD is the leading cause of blindness for people over the age of 65 in the U.S. and Europe.  It is estimated that more than 210,000 Americans are newly diagnosed with and treated for wet AMD each year.About Central Retinal Vein Occlusion (CRVO)Over 100,000 people in the United States and more than 66,000 people in key European countries are estimated to suffer from central retinal vein occlusion (CRVO).  CRVO is caused by obstruction of the central retinal vein that leads to a back up of blood and fluid in the retina.  This causes retinal injury and loss of vision.  The retina can also become "ischemic" (starved for oxygen), resulting in the growth of new, inappropriate blood vessels that can cause further vision loss and more serious complications.  Release of vascular endothelial growth factor (VEGF) contributes to increased vascular permeability in the eye and inappropriate new vessel growth.  It is believed that anti-VEGF treatment may help decrease vascular permeability and edema and prevent the inappropriate growth of new blood vessels in the retina in patients with CRVO.About Diabetic Macular Edema (DME)Diabetic macular edema (DME) is the most prevalent cause of moderate vision loss in patients with diabetes.  DME is a common complication of Diabetic Retinopathy (DR), a disease affecting the blood vessels of the retina.  Clinically significant DME is a leading cause of blindness in younger adults (under 50).  Clinically significant DME occurs when fluid leaks into the center of the macula, the light-sensitive part of the retina responsible for sharp, direct vision.  Fluid in the macula can cause severe vision loss or blindness.Approximately 370,000 Americans currently suffer from clinically significant DME, with 95,000 new cases arising each year.  According to the American Diabetes Association, more than 18 million Americans currently suffer from diabetes, and many other people are at risk for developing diabetes.  With the incidence of diabetes steadily climbing, it is projected that up to 10 percent of all patients with diabetes will develop DME during their lifetime.About Regeneron PharmaceuticalsRegeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions.  In addition to ARCALYST® (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has therapeutic candidates in Phase 3 clinical trials for the potential treatment of gout, diseases of the eye (wet age-related macular degeneration and central retinal vein occlusion), and certain cancers.  Additional therapeutic candidates developed from proprietary Regeneron technologies for creating fully human monoclonal antibodies are in earlier stage development programs in rheumatoid arthritis and other inflammatory conditions, pain, cholesterol reduction, allergic and immune conditions, and cancer.  Additional information about Regeneron and recent news releases are available on Regeneron's web site at www.regeneron.com. Regeneron Forward Looking StatementThis news release includes forward-looking statements about Regeneron and its products, development programs, finances, and business, all of which involve a number of risks and uncertainties.  These include, among others, risks and timing associated with preclinical and clinical development of Regeneron's drug candidates, determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize its product and drug candidates, competing drugs that are superior to Regeneron's product and drug candidates, uncertainty of market acceptance of Regeneron's product and drug candidates, unanticipated expenses, the availability and cost of capital, the costs of developing, producing, and selling products, the potential for any license or collaboration agreement, including Regeneron's agreements with the sanofi-aventis Group and Bayer HealthCare, to be canceled or terminated without any product success, and risks associated with third party intellectual property.  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 (SEC), including its Form 10-K for the year ended December 31, 2010. 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.Investor Relations Contact:Michael Aberman, M.D. Tel. +1 (914) 345-7799E-Mail: michael.aberman@regeneron.com Media Contact:Peter Dworkin, Tel. +1 (914) 345-7640E-Mail: peter.dworkin@regeneron.comSOURCE Regeneron Pharmaceuticals, Inc.For further information: Investor Relations Contact: Michael Aberman, M.D., +1-914-345-7799, michael.aberman@regeneron.com, or Media Contact: Peter Dworkin, +1-914-345-7640, peter.dworkin@regeneron.com