VEGF Trap-Eye Shows Positive Results in a Phase 2 Study in Patients With Diabetic Macular Edema
`
`February 18, 2010
`
`TARRYTOWN, N.Y. and LEVERKUSEN, Germany, Feb 18, 2010 /PRNewswire via COMTEX News Network/ -- Regeneron Pharmaceuticals, Inc.
`(Nasdaq: REGN) and Bayer HealthCare AG today announced that VEGF Trap-Eye showed positive results in a Phase 2 study in patients with diabetic
`macular edema (DME). The primary endpoint of the study, a statistically significant improvement in visual acuity over 24 weeks compared to the
`standard of care in DME, macular laser therapy, was met. Visual acuity improvement was measured by the mean number of letters gained over the
`initial 24 weeks of the study.
`
`"The ability of VEGF Trap-Eye to significantly improve vision in patients with DME in this initial Phase 2 study is encouraging," said Dr. Kemal Malik,
`member of the Bayer HealthCare Executive Committee responsible for global development. "Bayer and Regeneron will discuss the next steps in
`further developing VEGF Trap-Eye in this indication."
`
`"The magnitude of the gain in visual acuity achieved with VEGF Trap-Eye in this Phase 2 study demonstrates the biologic activity of VEGF Trap-Eye in
`treating diabetic macular edema, a disease in which high levels of vascular endothelial growth factor (VEGF) are present," said Diana Do, MD, the
`Principal Investigator for the study and Assistant Professor of Ophthalmology at the Wilmer Eye Institute, The Johns Hopkins University School of
`Medicine in Baltimore, Maryland.
`
`Patients in each of the four dosing groups receiving VEGF Trap-Eye achieved statistically significantly greater mean improvements in visual acuity (8.5
`to 11.4 letters of vision gained) compared to patients receiving macular laser therapy (2.5 letters gained) at week 24 (p< 0.01 for each VEGF Trap-Eye
`group versus laser). VEGF Trap-Eye was generally well tolerated, and there were no drug-related serious adverse events.
`
`The results of the Phase 2 study will be presented at the Angiogenesis 2010: Clinical Trials meeting on February 20, 2010 in Miami, Florida. Slides
`summarizing the data presented will be made available at that time on the Regeneron website (www.regeneron.com on the Presentations Page, under
`the Investor Relations section).
`
`About the Phase 2 Study Results
`
`In this double-masked, prospective, randomized, multi-center Phase 2 trial, entitled DA VINCI (DME And VEGF Trap-Eye: INvestigation of Clinical
`Impact), 219 patients with clinically significant DME with central macular involvement were randomized to five groups. The control group received
`macular laser therapy at week one, and patients were eligible for repeat laser treatments, but no more frequently than at 16 week intervals. Two
`groups received monthly doses of 0.5 or 2.0 milligrams (mg) of VEGF Trap-Eye throughout the 6-month dosing period. Two groups received three
`initial monthly doses of 2.0 mg of VEGF Trap-Eye (at baseline and weeks 4 and 8), followed through week 24 by either every 8-week dosing or
`as-needed (PRN) dosing with specific repeat dosing criteria. The following summarizes the mean gain in visual acuity at week 24 by dosing arm and
`the mean number of treatments received by patients over the first six monthly visits:
`
`Standard-of-care macular laser therapy (n=44; 1.7 treatments): +2.5 letters gained
`VEGF Trap Eye 0.5 mg monthly (n=44; 5.6 injections): +8.6 letters gained
`VEGF Trap-Eye 2 mg monthly (n=44; 5.5 injections): +11.4 letters gained
`VEGF Trap-Eye 2 mg every other month, following 3 monthly injections (n=42: 3.8 injections): +8.5 letters gained
`VEGF Trap-Eye 2 mg as-needed, following 3 monthly injections (n=45; 4.4 injections): +10.3 letters gained
`
`The study was not designed to evaluate statistical differences among the results achieved in each of the VEGF Trap-Eye groups, and no significant
`differences were observed. Over 90 percent of the VEGF Trap-Eye patients and the laser patients remained in the study at the 6-month primary
`endpoint evaluation.
`
`VEGF Trap-Eye was generally well-tolerated, and there were no ocular or non-ocular drug-related serious adverse events reported in the study. The
`adverse events reported were those typically associated with intravitreal injections or the underlying disease. The most frequent adverse events
`reported among patients receiving VEGF Trap-Eye included conjunctival hemorrhage, eye pain, floaters (myodesopsia), ocular redness (hyperemia),
`and increased intraocular pressure. There were three deaths among the 175 patients treated with VEGF Trap-Eye and none in the 44 patients treated
`with laser over 6 months. All three patients had underlying risk factors for their cause of death, and the cases were not reported to be drug-related.
`
`Following the initial 24 weeks of treatment, patients continue to be treated for another 24 weeks on the same dosing regimens. Initial one-year results
`will be available later this year. Regeneron and Bayer HealthCare are sponsors of the DA VINCI study.
`
`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.
`
`Mylan Exhibit 1057
`Mylan v. Regeneron, IPR2021-00881
`Page 1
`
`Joining Petitioner: Apotex
`
`

`

`About VEGF Trap-Eye
`
`VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein 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 currently in Phase 3 development in wet (age-related) macular degeneration (AMD). The VIEW 1 (VEGF Trap-Eye: Investigation of
`Efficacy and Safety in Wet AMD) study is being conducted in the United States and Canada by Regeneron and the VIEW 2 study is being conducted in
`Europe, Asia Pacific, Japan, and Latin America by Bayer HealthCare. The primary endpoint of these non-inferiority studies is the proportion of patients
`treated with VEGF Trap-Eye who maintain vision at the end of one year, compared to ranibizumab patients. Patient enrollment has been completed in
`both studies with initial year-one primary endpoint data expected in the second half of 2010.
`
`VEGF Trap-Eye is also in Phase 3 development for the treatment of central retinal vein occlusion (CRVO), another major cause of blindness. The
`COPERNICUS (COntrolled Phase 3 Evaluation of Repeated iNtravitreal administration of VEGF Trap-Eye In Central retinal vein occlusion: Utility and
`Safety) study is being led by Regeneron, and the GALILEO (General Assessment Limiting InfiLtration of Exudates in central retinal vein Occlusion
`with VEGF Trap-Eye) study is being led by Bayer HealthCare. The primary endpoint of both studies is improvement in visual acuity versus baseline
`after six months of treatment. Initial data from the CRVO program are anticipated in early 2011.
`
`About Regeneron Pharmaceuticals, Inc.
`
`Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious
`medical conditions. In addition to ARCALYST(R) (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has
`therapeutic candidates in Phase 3 clinical trials for the potential treatment of gout, age-related macular degeneration, and certain cancers. Additional
`therapeutic candidates are in earlier stage development programs in rheumatoid arthritis and other inflammatory conditions, pain, cholesterol
`reduction, allergic conditions, and cancer. Additional information about Regeneron and recent news releases are available on Regeneron's web site at
`www.regeneron.com.
`
`Forward Looking Statement - Regeneron
`
`This news release discusses historical information and includes forward-looking statements about Regeneron and its products, development
`programs, finances, and business, all of which involve a number of risks and uncertainties, such as risks 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 collaboration agreement, including Regeneron's
`agreements with the sanofi-aventis Group and Bayer HealthCare, to be canceled or to terminate without any product success, risks associated with
`third party intellectual property, and other material risks. 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, 2008 and Form
`10-Q for the quarter ending September 30, 2009. 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.
`
`About Bayer HealthCare Pharmaceuticals
`
`The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a
`subsidiary of Bayer AG, 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, Bayer Schering Pharma, Consumer Care and Medical Care
`divisions. Bayer HealthCare's aim is to discover and manufacture products that will improve human and animal health worldwide. Find more
`information at www.bayerhealthcare.com.
`
`Forward-Looking Statements - Bayer HealthCare AG
`
`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.
`
` Contact Information:(cid:10)
` Regeneron Pharmaceuticals, Inc.(cid:10)
` Peter Dworkin Laura Lindsay(cid:10)
` Investor Relations Media Relations(cid:10)
` 914.345.7640 914.345.7800(cid:10)
` peter.dworkin@regeneron.com laura.lindsay@regeneron.com(cid:10)
`
` Bayer HealthCare(cid:10)
` Anna Koch,(cid:10)
` +49 30 468-15942(cid:10)
` anna.koch@bayerhealthcare.com(cid:10)
`
`Mylan Exhibit 1057
`Mylan v. Regeneron, IPR2021-00881
`Page 2
`
`Joining Petitioner: Apotex
`
`

`

`SOURCE Regeneron Pharmaceuticals, Inc.
`
`Copyright (C) 2010 PR Newswire. All rights reserved
`
`Mylan Exhibit 1057
`Mylan v. Regeneron, IPR2021-00881
`Page 3
`
`Joining Petitioner: Apotex
`
`