2/4/22, 5:51 PM
`
`Regeneron Announces FDA Approval of EYLEA™ (aflibercept) Injection for the Treatment of Wet Age-Related Macular Degeneration: CORRECTED | Regeneron Pharmaceuticals Inc.
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`November 18, 2011 at 5:51 PM EST
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`REGENERON ANNOUNCES FDA APPROVAL OF EYLEA™ (AFLIBERCEPT) INJECTION FOR
`THE TREATMENT OF WET AGE-RELATED MACULAR DEGENERATION: CORRECTED
`
`In the news release, Regeneron Announces FDA Approval of EYLEA™ (aibercept) Injection for the Treatment of Wet
`Age-Related Macular Degeneration, issued 18-Nov-2011 by Regeneron Pharmaceuticals, Inc. over PR Newswire, the
`third paragraph, second sentence, should read "EYLEA offers the potential of achieving the ecacy we've come to
`expect from current anti-VEGF agents, but with less frequent injections and monitoring." The complete, corrected
`release follows:
`
` 
`TARRYTOWN, N.Y., Nov. 18, 2011 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) today
`announced that the U.S. Food and Drug Administration (FDA) has approved EYLEA(aibercept) Injection, known in
`the scientic literature as VEGF Trap-Eye, for the treatment of patients with neovascular (wet) Age-related Macular
`Degeneration (AMD) at a recommended dose of 2 milligrams (mg) every four weeks (monthly) for the rst 12 weeks,
`followed by 2 mg every eight weeks (2 months).
`
`The approval of EYLEA was granted under a Priority Review, a designation that is given to drugs that offer major
`advances in treatment, or provide a treatment where no adequate therapy exists.  This approval was based upon the
`results of two Phase 3 clinical studies.  In these studies, EYLEA dosed every eight weeks, following three initial
`monthly injections, was clinically equivalent to the standard of care, Lucentis® (ranibizumab injection) dosed every
`four weeks, as measured by the primary endpoint of maintenance of visual acuity (less than 15 letters of vision loss
`on an eye chart) over 52 weeks.  The most common adverse reactions (frequency of 5% or more) reported in patients
`receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous oaters, and
`increased intraocular pressure.  The adverse event prole was similar to that seen with ranibizumab.
`
`"The approval of EYLEA offers a much needed new treatment option for patients with wet AMD," said Jeffrey Heier,
`M.D., a clinical ophthalmologist and retinal specialist at Ophthalmic Consultants of Boston, Assistant Professor of
`Ophthalmology at Tufts School of Medicine, and Chair of the Steering Committee for the VIEW 1 trial.  "EYLEA offers
`the potential of achieving the ecacy we've come to expect from current anti-VEGF agents, but with less frequent
`injections and monitoring.  This may reduce the need for costly and time-consuming monthly oce visits for patients
`and their caregivers."
`
`"This approval is an important step forward for Regeneron and for patients suffering with wet AMD, the most
`common cause of blindness in the U.S. in older adults," said Leonard S. Schleifer, M.D., Ph.D., President and Chief
`Executive Ocer of Regeneron.  "We thank the patients and clinical investigators who participated in our clinical
`studies, the FDA, and the Regeneron employees who helped make this day possible.  Now that EYLEA is approved, we
`plan to make EYLEA available to patients within the next few days." 
`
`About EYLEA™ (aibercept) 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 ne-resolution central vision often results.  
`
`EYLEA, known in the scientic literature as VEGF Trap-Eye, 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 indicated for the treatment of patients with neovascular age-related macular degeneration (wet AMD). 
`BACK
`EYLEA is contraindicated in patients with ocular or periocular infections, active intraocular inammation, or known
`TO TOP
`hypersensitivity to aibercept or to any of the excipients in EYLEA.
`
`https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-fda-approval-eylea153-aflibercept-injection
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`1/4
`
`Exhibit 2116
`Page 01 of 04
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`

`

`2/4/22, 5:51 PM
`
`Regeneron Announces FDA Approval of EYLEA™ (aflibercept) Injection for the Treatment of Wet Age-Related Macular Degeneration: CORRECTED | Regeneron Pharmaceuticals Inc.
`The recommended dose for EYLEA is 2 mg administered by intravitreal injection every four weeks (monthly) for the
`rst 12 weeks (3 months), followed by 2 mg once every eight weeks (2 months).  Although EYLEA may be dosed as
`frequently as 2 mg every four weeks (monthly), additional ecacy was not demonstrated when EYLEA was dosed
`every four weeks compared to every eight weeks.
`
`There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors,
`including EYLEA, dened as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of
`unknown cause).  The incidence of ATEs with EYLEA in clinical trials was low (1.8%).
`
`Serious adverse reactions related to the injection procedure have occurred in less than 0.1% of intravitreal injections
`with EYLEA and include endophthalmitis, traumatic cataract, and increased intraocular pressure.
`
`About the VIEW 1 and VIEW 2 Clinical Studies
`
`The safety and ecacy of EYLEA were assessed in two randomized, multi-center, double-masked, active-controlled
`studies in patients with wet AMD.  A total of 2412 patients were treated and evaluable for ecacy (1817 with EYLEA)
`in the two studies (VIEW 1 and VIEW 2). In each study, patients were randomly assigned in a 1:1:1:1 ratio to one of
`four dosing regimens: 1) EYLEA administered 2 mg every eight weeks following three initial monthly doses (EYLEA
`2Q8); 2) EYLEA administered 2 mg every four weeks (EYLEA 2Q4); 3) EYLEA 0.5 mg administered every four weeks
`(EYLEA 0.5Q4); and 4) ranibizumab administered 0.5 mg every four weeks (ranibizumab 0.5Q4).  Patient ages ranged
`from 49 to 99 years with a mean of 76 years.
`
`In both studies, the primary ecacy endpoint was the proportion of patients who maintained vision, dened as losing
`fewer than 15 letters of visual acuity at week 52 compared to baseline.  Data are available through week 52.  Both the
`EYLEA™ (aibercept) Injection 2Q8 and 2Q4 dosing groups were shown to have ecacy that was clinically equivalent
`to the ranibizumab 0.5Q4 group for the primary endpoint.
`
`Select results of the VIEW 1 and VIEW 2 studies as described in the full Prescribing Information for the EYLEA 2 mg
`every four weeks and EYLEA 2 mg every eight weeks dosing groups as compared to ranibizumab dosed monthly
`group are shown below.
`
`Ecacy Outcomes at Week 52 (Full Analysis Set with LOCF) in VIEW 1 and VIEW 2 Studies
`
`
`
`EYLEA
`
`VIEW 1
`
`EYLEA
`
`ranibizu-mab
`
`EYLEA
`
`VIEW 2
`
`EYLEA
`
`ranibizu-mab
`
`
`
`Full Analysis Set
`
`2 mg Q8 weeks(a)
`
`2 mg Q4 weeks
`
`0.5 mg Q4 weeks
`
`2 mg Q8 weeks(a)
`
`2 mg Q4 weeks
`
`0.5 mg Q4 weeks
`
`N=301
`
`N=304
`
`N=304
`
`N=306
`
`N=309
`
`N=291
`
`Efficacy Outcomes
`
`Proportion of patients who maintained visual acuity (%)
`
`(<15 letters of BCVA loss)
`
`Difference(b) (%)
`
`(95.1% CI)
`
`Mean change in BCVA as measured by ETDRS letter score from Baseline
`
`Difference(b) in LS mean
`
`
`
`94%
`
`0.6
`
`95%
`
`1.3
`
`
`
`94%
`
`95%
`
`0.6
`
`95%
`
`-0.3
`
` (-3.2, 4.4)
`
` (-2.4, 5.0)
`
`
`
` (-2.9, 4.0)
`
` (-4.0, 3.3)
`
`
`
`7.9
`
`0.3
`
`10.9
`
`3.2
`
`8.1
`
`8.9
`
`-0.9
`
`7.6
`
`-2.0
`
`95%
`
`9.4
`
`(95.1% CI)
` (-2.0, 2.5)
`(0.9, 5.4)
`
` (-3.1, 1.3)
` (-4.1, 0.2)
`
`BCVA = Best Corrected Visual Acuity; CI = Condence Interval; ETDRS = Early Treatment Diabetic Retinopathy Study;
`LOCF = Last Observation Carried Forward (baseline values are not carried forward); 95.1% condence intervals were
`presented to adjust for safety assessment conducted during the study.
`(a) After treatment initiation with 3 monthly doses
`(b) EYLEA group minus the ranibizumab group
`
`IMPORTANT SAFETY INFORMATION
`
`EYLEA™ (aibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular
`inammation, or known hypersensitivity to aibercept 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.
`
`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.
`
`BACK
`There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors,
`TO TOP
`including EYLEA, dened as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of
`unknown cause).  The incidence of ATEs with EYLEA in clinical trials was low (1.8%).
`
`https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-fda-approval-eylea153-aflibercept-injection
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`2/4
`
`Exhibit 2116
`Page 02 of 04
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`

`

`2/4/22, 5:51 PM
`
`Regeneron Announces FDA Approval of EYLEA&#153; (aflibercept) Injection for the Treatment of Wet Age-Related Macular Degeneration: CORRECTED | Regeneron Pharmaceuticals Inc.
`Serious adverse reactions related to the injection procedure have occurred in less than 0.1% of intravitreal injections
`with EYLEA including endophthalmitis, traumatic cataract, and increased intraocular pressure.
`
`The most common adverse reactions (greater than or equal to 5%) reported in patients receiving EYLEA were
`conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous oaters, and increased intraocular
`pressure.
`
`Please see the full Prescribing Information for EYLEA, available online at www.regeneron.com/EYLEA-fpi.pdf.
`
`About the EYLEA™ (aibercept) Injection Global Collaboration
`
`Regeneron is collaborating with Bayer HealthCare on the global development of EYLEA.  Bayer submitted an
`application for marketing authorization in Europe for wet AMD in June 2011.
`
`Bayer HealthCare will market EYLEA outside the United States, where the companies will share equally the prots
`from any future sales of EYLEA.  Regeneron maintains exclusive rights to EYLEA in the United States.
`
`About 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 uid.  This leakage causes disruption and dysfunction of the retina creating distortion and/or
`blind spots in central vision.  Wet AMD is the leading cause of blindness for people over the age of 65 in the U.S. and
`Europe.
`
`Conference Call Information
`
`Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Ocer of Regeneron, and other members of senior
`management will host a conference call to discuss the FDA approval of EYLEA for the treatment of patients with wet
`AMD and launch plans, as well as other corporate matters.  The interactive call will be held on November 18, 2011 at
`6:30 p.m. Eastern Time and can be accessed live through the Regeneron website at www.regeneron.com on the
`Investor Relations page.  The call, including the question and answer session, can also be accessed by dialing:
`
`Domestic Dial-in Number:  (888) 660-6127
`International Dial-in Number:  (973) 890-8355
`Participant Passcode:  30193445
`
`An archived version of the conference call will be available for 30 days on the company's website at
`www.regeneron.com on the Investor Relations page.
`
`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 two products,
`ARCALYST (rilonacept) Injection For Subcutaneous Use and EYLEA™ (aibercept) Injection.  Regeneron also has
`®
`completed several Phase 3 studies and is conducting an additional Phase 3 clinical trial for the product candidate
`ZALTRAP (aibercept) Concentrate for Intravenous Infusion.  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 inammatory conditions, pain, cholesterol reduction, allergic and immune
`conditions, and cancer.  Additional information about Regeneron and recent news releases are available on the
`Regeneron web site at www.regeneron.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 EYLEA and Regeneron's product candidates and
`research and clinical programs now underway or planned, 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 EYLEA and other products and drug candidates, competing drugs that may be superior to EYLEA and
`Regeneron's products and drug candidates, uncertainty of market acceptance of EYLEA and Regeneron's products
`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
`Sano and Bayer HealthCare, to be canceled or terminated without any product success, and risks associated with
`third party intellectual property and pending or future litigation relating thereto.  A more complete description of
`BACK
`these and other material risks can be found in Regeneron's lings with the United States Securities and Exchange
`TO TOP
`Commission, including its Form 10-K for the year ended December 31, 2010 and Form 10-Q for the quarter ended
`September 30, 2011.  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.
`
`https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-fda-approval-eylea153-aflibercept-injection
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`Exhibit 2116
`Page 03 of 04
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`

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`2/4/22, 5:51 PM
`
`Regeneron Announces FDA Approval of EYLEA&#153; (aflibercept) Injection for the Treatment of Wet Age-Related Macular Degeneration: CORRECTED | Regeneron Pharmaceuticals Inc.
`Contact Information:
` 
`Michael Aberman, M.D.
`Investor Relations 
`914.847.7799
`michael.aberman@regeneron.com
`SOURCE Regeneron Pharmaceuticals, Inc.
`
`Peter Dworkin
`Corporate Communications
`914.847.7640                       
`peter.dworkin@regeneron.com
`
`News Provided by Acquire Media
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`BACK
`TO TOP
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`Exhibit 2116
`Page 04 of 04
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