UNITED STATES INTERNATIONAL TRADE COMMISSION
`WASHINGTON, D.C.
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`Investigation No. 337-TA-____
`Docket No. 3460
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`In the Matter of
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`CERTAIN PRE-FILLED SYRINGES FOR
`INTRAVITREAL INJECTION AND
`COMPONENTS THEREOF
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`STATEMENT ON THE PUBLIC INTEREST BY PROPOSED
`RESPONDENT REGENERON PHARMACEUTICALS, INC.
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`Regeneron Exhibit 1085.001
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`Proposed Respondent Regeneron Pharmaceuticals, Inc. respectfully submits this public interest
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`statement in response to a complaint entitled Certain Pre-filled Syringes for Intravitreal Injection and
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`Components Thereof, DN 3460, filed on June 19, 2020. See 85 Fed. Reg. 38158. As discussed below, the
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`relief sought in the Complaint would be severely detrimental to the public health because it would disrupt
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`the treatment regimens for patients suffering from serious eye diseases, eliminate physician choice to
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`ensure the best therapies for their patients, and force patients benefiting from the accused product to
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`switch to other drugs that are less effective and in some cases even unsafe.
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`I.
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`HOW THE ACCUSED PRODUCTS ARE USED IN THE UNITED STATES
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`Complainants seek to bar the importation of Regeneron’s EYLEA® (aflibercept) pre-filled
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`syringe (“PFS”) and components thereof. EYLEA is an innovative biologic drug for the treatment of a
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`variety of severe eye diseases involving overproduction of a naturally occurring protein called vascular
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`endothelial growth factor (“VEGF”). Millions of patients suffer from VEGF-related eye diseases that can
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`cause vision loss and blindness, including (among others) wet age-related macular degeneration (“wet
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`AMD”), diabetic retinopathy (“DR”), diabetic macular edema (“DME”), and macular edema following
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`retinal vein occlusion (“MEfRVO”). EYLEA is FDA-approved to treat all of these diseases.
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`EYLEA is a novel and groundbreaking drug developed by Regeneron that blocks or inhibits the
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`overproduction of VEGF proteins, reducing abnormal growth and leakage in the eye, which helps to
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`stabilize vision loss. In some cases, EYLEA can even reverse vision loss and restore sight. After years of
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`research and development, EYLEA first received FDA approval in vial form in November 2011. FDA
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`approved EYLEA in PFS form on August 13, 2019. Regeneron started selling EYLEA PFS on December
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`9, 2019, and commenced a full-scale commercial launch in February 2020. After only months on the
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`market, physicians and patients rapidly switched from EYLEA vial to EYLEA PFS, with nearly 80% of
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`EYLEA sales converting to PFS form. Nearly all EYLEA sales will likely convert to PFS within the year.
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`II.
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`THE REQUESTED RELIEF POSES SUBSTANTIAL PUBLIC HEALTH CONCERNS
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`A. Patients Should Not Be Forced to Switch to EYLEA in Vial Form
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`Complainants contend that excluding EYLEA PFS would have no adverse impact on the public
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`1
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`Regeneron Exhibit 1085.002
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`health because physicians can simply switch from administering EYLEA PFS to EYLEA with a vial and
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`syringe – this is simply untrue for several reasons. First, as shown in Fig. A below, EYLEA in vial form
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`comes with many more components than PFS, including the vialed biologic, two separate needles, a
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`plastic syringe, and not to mention all the packaging.
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`Fig. A: EYLEA Vial
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` Fig. B. EYLEA PFS
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`Thus a physician must utilize two needles, along with the vialed biologic, to undergo the sterile process of
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`withdrawing the anti-VEGF from the vial (using a filter needle) before injecting it into the patient’s eye
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`(using an injection needle). By contrast, the PFS (shown in Fig. B above) is a single, integrated safety
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`system injection product and comes ready-to-use as soon as the physician attaches a separate needle for
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`injection. Thus, administering EYLEA in vial form, by definition, has more touch points, is more time-
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`consuming, increases the number of steps and thereby the possibility of foreign particles being introduced
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`into the eye during administration. It is no surprise that physicians as well as patients prefer the PFS over
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`the vial given its ease of use and efficiency.
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`Moreover, switching the many millions of patients now relying on their regular injections of
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`EYLEA PFS to injection with a separate needle from a vial would be impractical from a supply
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`standpoint. Regeneron and its manufacturing partners have already transitioned their manufacturing and
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`supply operations from EYLEA in the vial to EYLEA in PFS. To transition the manufacturing process
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`back to the EYLEA vial would take several years to accomplish, assuming the manufacturing lines are
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`2
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`Regeneron Exhibit 1085.003
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`even available. If those manufacturing lines are not available and Regeneron were forced to develop new
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`manufacturing partners or facilities, the process of procuring equipment, developing and validating the
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`manufacturing process, and obtaining regulatory approval would take even longer. As such, Regeneron
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`cannot predict when or how many EYLEA vials would be available for patients currently relying on
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`EYLEA PFS. EYLEA in vial form is thus not an acceptable substitute for EYLEA PFS.
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`B. LUCENTIS Is Less Effective and Less Convenient than EYLEA PFS
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`There is no acceptable substitute for EYLEA PFS. Complainants contend that their own anti-
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`VEGF product LUCENTIS is an acceptable substitute. But Lucentis requires more frequent injections
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`than EYLEA at a time when in-patient trips to medical doctors are difficult with the COVID-19
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`pandemic. Unlike LUCENTIS, EYLEA is recommended for intravitreal injection once a month for the
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`first three months, but then can be injected every two months to treat wet AMD, DR, and DME.
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`Regeneron clinical studies showed that EYLEA administered every two months was clinically equivalent
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`to LUCENTIS dosed monthly. Indeed, EYLEA involves “less frequent injections and monitoring. This
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`may reduce the need for costly and time-consuming monthly visits for patients and caregivers.”1
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`Moreover, because of its unique design, EYLEA is likely to bind the VEGF target more tightly than
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`LUCENTIS (which has only one VEGF binding domain), resulting in a stronger inhibition of VEGF in
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`the patients’ eyes. EYLEA has also been found to be more effective at improving vision for patients with
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`DME.2 EYLEA is therefore regarded by many as superior to LUCENTIS.
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`LUCENTIS is not an acceptable substitute for EYLEA PFS for the additional reason that
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`physicians are naturally reluctant to switch a patient from one anti-VEGF to another when the patient is
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`responding well to a particular treatment. Moreover, insurance approval for EYLEA is not transferable to
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`LUCENTIS, so patients would experience additional delays and inconvenience if they were forced to
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`1 Press Release, Regeneron, “Regeneron Announces FDA Approval of EYLEA™ (aflibercept) Injection
`for the Treatment of Wet Age-Related Macular Degeneration,” (Nov. 18, 2011),
`https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-fda-approval-
`eylea153-aflibercept-injection.
`2 See Diabetic Retinopathy Clinical Research Network, Aflibercept, Bevacizumab, or Ranibizumab for
`Diabetic Macular Edema, N. Engl. J. Med. 372(13) (Mar. 26, 2015).
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`3
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`Regeneron Exhibit 1085.004
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`switch treatment.
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`III.
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`OTHER FDA-APPROVED DRUGS CANNOT REPLACE EYLEA PFS
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`Aside from EYLEA in the vial and LUCENTIS, Complainants identify no other FDA-approved
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`anti-VEGF drugs for ophthalmic diseases at issue. Indeed, the only other such product that is prescribed
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`with any meaningful regularity is Complainants’ own anti-VEGF product BEOVU, and only for wet
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`AMD. But within months of BEOVU’s launch in 2019, patients started suffering from a range of severe
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`safety issues. Physicians immediately began reporting serious adverse reactions experienced by BEOVU
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`patients, including higher rates of intraocular inflammation, incidences of retinal artery occlusion, and
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`occlusive retinal vasculitis. These are urgent medical conditions that can result in permanent blindness. In
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`fact, Novartis’s own worldwide brand medical director urged Novartis to disclose its clinical study data
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`regarding the adverse health effects of BEOVU. Instead, Novartis terminated her employment, and a
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`wrongful termination suit is currently pending in the District of New Jersey. See Butuner v. Novartis
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`Pharm. Corp., Case No. 19-cv-06590-ES-MAH (D.N.J.).
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`Moreover, the American Society of Retinal Specialists has released five safety bulletins this year,
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`advising physicians that it had received reports of severe inflammation in patients injected with BEOVU.3
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`In response, Novartis conducted an external safety review of BEOVU, examining post-marketing events
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`in patients compared to its clinical trial results. Novartis ultimately sought FDA approval of an updated
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`label for BEOVU, highlighting its safety risks. FDA forced Novartis to acknowledge that BEOVU may
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`cause adverse events in patients of “retinal vasculitis and/or retinal vascular occlusion that may result in
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`severe vision loss.”4 BEOVU is thus not an acceptable replacement for EYLEA PFS, which has
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`experienced no such safety issues.
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`IV.
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`NO SUPPLIER HAS THE CAPACITY TO REPLACE THE ACCUSED PRODUCTS
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`For the reasons stated above, no supplier has the capacity to provide a safe, acceptable
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`3 See ASRS, Clinical Updates, https://www.asrs.org/clinical/clinical-updates.
`4 Press Release, Novartis, “Novartis Completes Safety Review and Initiates Update to the Beovu®
`Prescribing Information Worldwide (Apr. 8, 2020), https://www.novartis.com/news/novartis-completes-
`safety-review-and-initiates-update-beovu-prescribing-information-worldwide (emphasis added).
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`4
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`Regeneron Exhibit 1085.005
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`replacement anti-VEGF product that is FDA-approved and has the benefits of EYLEA PFS. Beyond the
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`serious patient and physician choice concerns, the capacity issues with manufacturing EYLEA in vial
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`form, and the safety and efficacy issues implicated by the Complaint, it does not appear that either
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`Novartis or its licensee Genentech have articulated how they could supply enough PFS (either with
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`LUCENTIS or BEOVU, assuming Novartis obtains regulatory approval) to replace EYLEA PFS.
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`V.
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`THE REQUESTED RELIEF WOULD ADVERSELY IMPACT U.S. CONSUMERS
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`Many millions of our country’s most vulnerable elderly patients rely on regular EYLEA PFS
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`injections, and the care and treatment decisions for these patients are properly with the treating physician.
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`That critical treatment choice should not be taken away. The requested relief would deprive patients of
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`EYLEA PFS and all of its benefits, forcing them to choose between an inferior treatment that requires
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`more frequent injections into a patient’s eye (LUCENTIS PFS), Novartis’ newest treatment that has
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`resulted in serious adverse reactions and even blindness in patients (BEOVU), or forced conversion back
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`to vial form. These concerns are all the more powerful during the present global COVID-19 pandemic
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`that has created much more significant health risks to individuals in need of anti-VEGF treatments and
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`adding to that risk by removing this key therapy would cause substantial public harm. Indeed, serious eye
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`disease disproportionately affects the elderly and those with medical conditions that exacerbate
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`complications associated with COVID-19. The proposed relief would unfairly subject those patients to
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`more frequent visits to medical facilities with LUCENTIS. Patients should not be forced to make that
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`harmful choice to protect Complainants’ patent rights.
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`VI.
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`CONCLUSION
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`The above considerations demonstrate that exclusion of EYLEA PFS would be detrimental to the
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`public health. Although Novartis contends otherwise, its credibility on this point is suspect. Novartis has
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`known about EYLEA PFS for six months, yet waited until the safety disaster with BEOVU to seek
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`exclusion of Regeneron’s vastly superior product. At a minimum, full discovery on these points is
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`warranted. Accordingly, Regeneron respectfully requests that the ITC decline to institute an investigation.
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`In the alternative, Regeneron requests that the Commission delegate public interest to the ALJ.
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`5
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`Regeneron Exhibit 1085.006
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`Dated: July 6, 2020
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`Respectfully submitted,
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`/s/ Elizabeth Stotland Weiswasser
`Elizabeth Stotland Weiswasser
`Anish R. Desai
`Natalie Kennedy
`Andrew Gesior
`WEIL, GOTSHAL & MANGES LLP
`767 Fifth Avenue
`New York, New York 10153
`Telephone: (212) 310-8000
`elizabeth.weiswasser@weil.com
`anish.desai@weil.com
`natalie.kennedy@weil.com
`andrew.gesior@weil.com
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`Brian E. Ferguson
`Robert T. Vlasis
`Christopher Pepe
`WEIL, GOTSHAL & MANGES LLP
`2001 M Street, NW, Suite 600
`Washington, DC 20036
`(202) 682-7000
`brian.ferguson@weil.com
`robert.vlasis@weil.com
`christopher.pepe@weil.com
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`Counsel for Proposed Respondent
`Regeneron Pharmaceuticals, Inc.
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`Regeneron Exhibit 1085.007
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`CERTIFICATE OF SERVICE
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`I hereby certify that a copy of the foregoing document was served on July 6, 2020, as indicated,
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`on the following:
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`Via EDIS
`The Honorable Lisa R. Barton
`Secretary to the Commission
`U.S. International Trade Commission
`500 E Street, S.W., Room 112
`Washington, D.C. 20436
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`Via Electronic Mail
`Margaret MacDonald
`Office of Unfair Import Investigations
`U.S. International Trade Commission
`500 E Street, S.W.
`Washington, D.C. 20436
`margaret.macdonald@usitc.gov
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`Elizabeth J. Holland
`Linnea P. Cipriano
`Calvin E. Wingfield Jr.
`Goodwin Procter LLP
`The New York Times Building
`620 Eighth Avenue
`New York, NY 10018-1405
`Phone: (212) 813-8800
`Fax: (212) 355-3333
`eholland@goodwinlaw.com
`lcipriano@goodwinlaw.com
`cwingfield@goodwinlaw.com
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`Mark G. Davis
`William G. James
`Patrick J. McCarthy
`Myomi T. Coad
`Goodwin Procter LLP
`1900 N St., N.W
`Washington, D.C. 20036-1612
`Phone: (202) 346-4000
`Fax: (202) 346-4444
`markdavis@goodwinlaw.com
`wjames@goodwinlaw.com
`pmccarthy@goodwinlaw.com
`mcoad@goodwinlaw.com
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`Joshua Weinger
`Goodwin Procter LLP
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`7
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`Regeneron Exhibit 1085.008
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`100 Northern Avenue
`Boston, MA 02210
`Phone: (617) 570-1000
`Fax: (617) 523-1231
`jweinger@goodwinlaw.com
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`Counsel for Complainants Novartis Pharma AG, Novartis Pharmaceuticals Corporation, and Novartis
`Technology LLC
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`Respectfully Submitted,
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`/s/Lauren McDuffie
`Lauren McDuffie
`IP Paralegal
`Weil, Gotshal & Manges LLP
`2001 M Street, NW, Suite 600
`Washington, D.C. 20036
`lauren.mcduffie@weil.com
`202.682.7000
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`8
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`Regeneron Exhibit 1085.009
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