VEGF Trap-Eye Final Phase 2 Results in Age-related Macular Degeneration Presented at 2008 Retina
`Society Meeting
`
`September 28, 2008
`VEGF Trap-Eye Final Phase 2 Results in Age-related Macular Degeneration Presented at 2008 Retina Society Meeting
`
`SCOTTSDALE, Ariz., Sep 28, 2008 (BUSINESS WIRE) -- Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) and Bayer HealthCare AG announced
`that VEGF Trap-Eye achieved durable improvements in visual acuity and in biologic measures of neovascular disease, including retinal thickness and
`active choroidal neovascularization lesion size, for up to one year in a Phase 2 study in the neovascular form of Age-related Macular Degeneration
`(wet AMD). The results were reported today in two oral presentations at the 2008 annual meeting of the Retina Society in Scottsdale, Arizona. Slides,
`including data reported at the presentations, are available on the Regeneron website (www.regeneron.com on the Presentations Page, under the
`Investor Relations section).
`
`In this double-masked Phase 2 trial, patients were initially treated with either fixed monthly or quarterly dosing for 12 weeks and then continued to
`receive treatment for another 40 weeks on a PRN (as needed) dosing schedule. Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or
`0.5 milligrams (mg) for 12 weeks followed by PRN dosing achieved mean improvements in visual acuity versus baseline of 9.0 letters (p<0.0001
`versus baseline) and 5.4 letters (p<0.085 versus baseline), respectively, at the end of one year. The proportion of patients with vision of 20/40 or better
`(part of the legal minimum requirement for an unrestricted driver's license in the U.S.) increased from 23 percent at baseline to 45 percent at week 52
`in patients initially treated with 2.0 mg monthly and from 16 percent at baseline to 47 percent at week 52 in patients initially treated with 0.5 mg
`monthly. During the week 12 to week 52 PRN dosing period, patients initially dosed on a 2.0 mg monthly schedule received, on average, only 1.6
`additional injections and those initially dosed on a 0.5 mg monthly schedule received, on average, 2.5 injections.
`
`Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 mg for 12 weeks followed by PRN dosing also achieved mean decreases in
`retinal thickness versus baseline of 143 microns (p<0.0001 versus baseline) and 125 microns (p<0.0001 versus baseline) at week 52, respectively.
`
`While PRN dosing following a fixed quarterly dosing regimen (with dosing at baseline and week 12) also yielded improvements in visual acuity and
`retinal thickness versus baseline at week 52, the results generally were not as robust as those obtained with initial fixed monthly dosing.
`
`"Anti-VEGF therapy has dramatically changed the treatment paradigm for wet AMD, and improvement in visual acuity is now feasible in most patients.
`The biggest challenge we have is that with our current drugs, the majority of patients need frequent injections into their eye to maintain their visual
`acuity gains," stated David M. Brown, M.D., a study investigator and a retinal specialist at The Methodist Hospital in Houston. "These study results
`reinforce our interest in further exploring whether continued administration of VEGF Trap-Eye on an as-needed basis after an initial period of fixed
`dosing can maintain a durability of effect over time in controlled Phase 3 clinical studies."
`
`In this Phase 2 study VEGF Trap-Eye was also associated with a reduction in the size of the total active choroidal neovascular membrane (CNV), the
`active lesion that is the underlying cause of vision loss in patients with wet AMD. Patients initially receiving either a 2.0 mg or 0.5 mg monthly fixed
`dose of VEGF Trap-Eye for 12 weeks followed by PRN dosing experienced statistically significant 3.41 mm(2) and 1.42 mm(2) reductions in mean
`CNV size at 48 weeks (the final one-year analysis from the independent reading center) versus baseline, respectively. Patients in the 2.0 mg monthly
`cohort also achieved a statistically significant 1.75 mm(2) reduction in total lesion size. A reduction in total lesion size was not seen in the cohort
`initially dosed with 0.5 mg monthly.
`
`"Progression of the active CNV lesion and resulting vision impairment are inevitable consequences of untreated wet AMD. The reduction in total active
`CNV lesion size achieved with VEGF Trap-Eye treatment in this Phase 2 clinical study could potentially translate into clinically meaningful outcomes in
`the larger, controlled Phase 3 studies that are underway," stated Jason Slakter, M.D., head of the independent reading center for the study and a
`Clinical Professor of Ophthalmology, New York University School of Medicine, New York.
`
`VEGF Trap-Eye was generally well tolerated and there were no drug-related serious adverse events. There was one reported case of culture-negative
`endophthalmitis/uveitis in the study eye, which was deemed not to be drug-related. The most common adverse events were those typically associated
`with intravitreal injections.
`
`"These study results confirm the rationale for our Phase 3 clinical program for VEGF Trap-Eye in wet AMD," said George D. Yancopoulos, M.D., Ph.D.,
`President of Regeneron Research Laboratories. "These trials are designed to optimize improvement in visual acuity with fixed-dosing regimens of
`either every 4 weeks or every 8 weeks for one year and then study how these vision improvements can be maintained with as-needed dosing in the
`second year."
`
`About the Phase 2 Study in Wet AMD
`
`In the double-masked, prospective, randomized, multi-center Phase 2 trial, 157 patients were randomized to five dose groups and treated with VEGF
`Trap-Eye in one eye. Two groups initially received monthly doses of 0.5 or 2.0 milligrams (mg) of VEGF Trap-Eye (at weeks 0, 4, 8, and 12) and three
`groups received quarterly doses of 0.5, 2.0, or 4.0 mg of VEGF Trap-Eye (at baseline and week 12). Following the initial 12-week fixed-dosing phase
`of the trial, patients continued to receive therapy at the same dose on a PRN dosing schedule based upon the physician assessment of the need for
`re-treatment in accordance with pre-specified criteria. Patients were monitored for safety, retinal thickness, and visual acuity. The primary endpoint
`results from the fixed dosing period were presented at the 2007 Retina Society conference in September 2007. Week 32 results were presented at the
`2008 Association for Research in Vision and Ophthalmology annual meeting in April 2008.
`
`About the Phase 3 Program in Wet AMD
`
`Mylan Exhibit 1056
`Mylan v. Regeneron, IPR2021-00881
`Page 1
`
`Joining Petitioner: Apotex
`
`

`

`Regeneron and Bayer HealthCare initiated a Phase 3 global development program for VEGF Trap-Eye in wet AMD in August 2007. In two Phase 3
`trials, the companies are evaluating VEGF Trap-Eye dosed 0.5 mg every 4 weeks, 2 mg every 4 weeks, or 2 mg every 8 weeks (following three
`monthly doses) in direct comparison with ranibizumab (Lucentis®, a registered trademark of Genentech, Inc.) administered 0.5 mg every 4 weeks
`according to its U.S. label during the first year of the studies. PRN dosing will be evaluated during the second year of each study. The VIEW1 study is
`currently enrolling patients in the United States and Canada and the VIEW2 study is currently enrolling patients in Europe, Asia Pacific, Japan, and
`Latin America. The companies are collaborating on the global development of VEGF Trap-Eye for the treatment of wet AMD, diabetic eye diseases,
`and other eye diseases and disorders. 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 VEGF Trap-Eye
`
`Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels
`(angiogenesis) to support the growth of the body's tissues and organs. It has also been associated with the abnormal growth and fragility of new blood
`vessels in the eye, which lead to the development of wet AMD. The 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. Blockade of VEGF, which can prevent abnormal blood vessel formation and vascular leak, has proven beneficial in the treatment of wet AMD.
`
`About Wet AMD
`
`Age-related Macular Degeneration (AMD) is a leading cause of acquired blindness. Macular degeneration is diagnosed as either dry (nonexudative) 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 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.
`
`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® (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has
`therapeutic candidates in clinical trials for the potential treatment of cancer, eye diseases, and inflammatory diseases and has preclinical programs in
`other diseases and disorders. Additional information about Regeneron and recent news releases are available on Regeneron's web site at
`www.regeneron.com.
`
`Forward Looking Statement
`
`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, 2007 and Form
`10-Q for the quarter ended June 30, 2008. 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.
`
`SOURCE: Regeneron Pharmaceuticals, Inc.
`
`Regeneron Pharmaceuticals, Inc.
`Investor Relations
`914-345-7640
`invest@regeneron.com
`or
`Laura Lindsay, 914-345-7800
`Corporate Communications
`laura.lindsay@regeneron.com
`or
`Kelly Hershkowitz, 212-845-5624
`Media Relations
`khershkowitz@biosector2.com
`
`Mylan Exhibit 1056
`Mylan v. Regeneron, IPR2021-00881
`Page 2
`
`Joining Petitioner: Apotex
`
`