Case 1:14-cv Document 1 Filed 02/27/14 Page 1 of 23 IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF COLUMBIA

Transcription

1 Case 1:14-cv Document 1 Filed 02/27/14 Page 1 of 23 IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF COLUMBIA ) AMARIN PHARMACEUTICALS ) IRELAND LIMITED ) 88 Harcourt Street ) Dublin 2, Ireland, ) ) Plaintiff, ) ) v. ) No. 1:14-cv-0324 ) FOOD AND DRUG ADMINISTRATION ) New Hampshire Avenue ) Silver Spring, MD 20993, ) ) MARGARET A. HAMBURG, M.D. ) Commissioner of Food and Drugs ) Food and Drug Administration ) New Hampshire Avenue ) Silver Spring, MD 20993, ) ) and ) ) KATHLEEN SEBELIUS ) Secretary of Health and Human Services ) 200 Independence Avenue, S.W. ) Washington, DC 20201, ) ) Defendants. ) ) COMPLAINT FOR DECLARATORY AND INJUNCTIVE RELIEF

2 Case 1:14-cv Document 1 Filed 02/27/14 Page 2 of 23 Plaintiff Amarin Pharmaceuticals Ireland Limited ( Amarin ) brings this Complaint against Defendants seeking declaratory and injunctive relief and alleges as follows: INTRODUCTION 1. Amarin is a pioneer biopharmaceutical company focused on developing and marking therapeutics to improve cardiovascular health. On July 26, 2012, Amarin secured the approval of the Food and Drug Administration ( FDA ) to market Vascepa (icosapent ethyl) Capsules ( Vascepa ) for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia. 2. Vascepa is Amarin s first FDA-approved product. Vascepa is also the first FDA-approved product with the active ingredient of icosapent ethyl, an ethyl ester of eicosapentaenoic acid, an omega-3 fatty acid. 3. Because FDA had never approved a product with icosapent ethyl as its active ingredient prior to its approval of Vascepa, Vascepa is entitled to a 5- year period of market exclusivity under Sections 505(c)(3)(E)(ii) and 505(j)(5)(F)(ii) of the Federal Food, Drug, and Cosmetic Act ( FDCA ), Pub. L. No , 52 Stat (1938), as amended by the Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No , 98 Stat ( Hatch- Waxman Act ) (codified as amended at 21 U.S.C. 355(c)(3)(E)(ii), 355(j)(5)(F)(ii)). 2

3 Case 1:14-cv Document 1 Filed 02/27/14 Page 3 of This statutory exclusivity protects pioneer drug companies from generic competition for five years after FDA s approval of an eligible pioneer drug and effectively prevents generic competitors from challenging the pioneer drug companies patents for four years after FDA approval. See 21 U.S.C. 355(c)(3)(E)(ii), 355(j)(5)(F)(ii). 5. However, on February 21, 2014, FDA informed Amarin that FDA had denied its request that the Agency recognize 5-year statutory exclusivity for Vascepa. See Ex. 1. FDA based its decision on FDA s prior approval of Lovaza, an undifferentiated fish oil mixture which FDA had approved in FDA acknowledged that the active ingredient in Lovaza is an undifferentiated fish oil mixture of which icosapent ethyl is only one of many constituents. Thus, FDA agreed with Amarin that Vascepa and Lovaza have different active ingredients. FDA nevertheless refused to recognize 5-year statutory exclusivity for Vascepa on the grounds that Lovaza s active ingredient is not also its active moiety and that Vascepa and Lovaza share a common active moiety. 7. FDA s decision is contrary to law. The controlling statutes grant 5- year exclusivity to any new drug, no active ingredient (including any ester or salt of the active ingredient) of which has been previously approved by FDA. It is undisputed that the active ingredient of Lovaza is an undifferentiated fish oil mixture. That mixture is not the same as Vascepa s active ingredient (icosapent ethyl). Nor is the mixture an ester or salt of icosapent ethyl, or vice versa. In refusing to recognize Vascepa s 5-year statutory exclusivity, FDA has improperly 3

4 Case 1:14-cv Document 1 Filed 02/27/14 Page 4 of 23 substituted the words active moiety for the statute s words ( active ingredient ). FDA has also concluded (in violation of the statute and regulations) that a drug with a complex mixture as its single active ingredient may have multiple active moieties, none of which is a salt or ester of the active ingredient. 8. FDA s action is also arbitrary and capricious. FDA has repeatedly recognized 5-year exclusivity for pioneer drugs in materially indistinguishable circumstances involving drug products with multiple constituents. In denying Amarin s request for similar treatment, FDA disowned these relevant Agency precedents and failed to offer a reasonable explanation for its reverse in policy or for applying its new approach retroactively to Vascepa. 9. FDA s application of its new policy retroactively to Vascepa s new drug application is particularly arbitrary and capricious because the product was entitled to 5-year exclusivity under existing Agency rules and practice during the time the product was developed and approved, as FDA itself initially recognized in reviewing the Vascepa product. In addition, Amarin was entitled to rely on the plain language of the governing statutes and on the FDA precedents recognizing such exclusivity in analogous situations that the Agency now maintains were wrongly decided. Amarin should not be penalized because after Amarin developed and secured approval for Vascepa FDA has decided to adopt a new policy that conflicts with its past practice. Indeed, on the very day that FDA relied on its new interpretation of the 5-year exclusivity statute and regulations to deny Amarin s request for 5-year exclusivity, FDA decided to apply a new interpreta- 4

5 Case 1:14-cv Document 1 Filed 02/27/14 Page 5 of 23 tion of the same statute and regulations only prospectively to other drug companies. See Citizen Petition Response, FDA-2013-P-0058, FDA-2013-P-0119, FDA P-0471, at 17 (Feb. 21, 2014). 10. FDA s application of its newly announced policy is also without observance of procedure required by law. FDA must continue to apply its past policy that the active moiety of a complex mixture is the mixture itself until FDA revises that interpretation of the applicable regulations through notice-andcomment rulemaking. 11. FDA s unlawful action upsets the careful balance that Congress struck between promoting competition among brand-name and generic drugs and encouraging innovation. FDA, Abbreviated New Drug Application Regulations; Patent and Exclusivity Provisions, 50,338, 50,338 (Oct. 3, 1994). It deprives Amarin of statutory exclusivity for Vascepa to which it is entitled, subjects Vascepa to generic challenges (in the form of abbreviated new drug application submissions and attendant litigation related to patents covering Vascepa) that the statute prohibits, and exposes Amarin to litigation costs and business risk that should not occur under the statute. Amarin therefore seeks an order (1) declaring that FDA s decision to deny Amarin s request for new chemical entity exclusivity violates the Administrative Procedure Act ( APA ), (2) declaring that Vascepa is entitled to the benefits of 5-year exclusivity under Sections 505(c)(3)(E)(ii) and 505(j)(5)(F)(ii) of the FDCA, (3) vacating FDA s decision, (4) enjoining FDA from accepting any application to market a generic version of 5

6 Case 1:14-cv Document 1 Filed 02/27/14 Page 6 of 23 Vascepa until after the expiration of Vascepa s new chemical entity exclusivity or until the Court so orders, and (5) setting aside FDA s acceptance of any such application that occurs before the Court enters its order. PARTIES 12. Plaintiff Amarin Pharmaceuticals Ireland Limited is incorporated and maintains its principal place of business in Ireland. 13. Defendant Food and Drug Administration is an agency of the United States Government within the Department of Health and Human Services, with offices at 200 Independence Avenue, S.W., Washington, DC, and New Hampshire Avenue, Silver Spring, MD. The Secretary of Health and Human Services has delegated to FDA the authority to administer the relevant provisions of the FDCA. 14. Defendant Margaret A. Hamburg, M.D., is Commissioner of Food and Drugs and is the senior official of the FDA. She is sued in her official capacity. Dr. Hamburg maintains offices at 200 Independence Avenue, S.W., Washington, DC, and New Hampshire Avenue, Silver Spring, MD. 15. Defendant Kathleen Sebelius is Secretary of Health and Human Services and the official charged by law with administering the FDCA. She is sued in her official capacity. Secretary Sebelius maintains an office at 200 Independence Avenue, S.W., Washington, DC. 6

7 Case 1:14-cv Document 1 Filed 02/27/14 Page 7 of 23 JURISDICTION AND VENUE 16. This action arises under the FDCA, 21 U.S.C. 301 et seq., and the APA, 5 U.S.C. 500 et seq. This Court has jurisdiction pursuant to 28 U.S.C. 1331, 1361, and There exists an actual and justiciable controversy between Amarin and Defendants requiring resolution by this Court. 18. Venue is proper pursuant to 28 U.S.C. 1391(e). STATUTORY AND REGULATORY BACKGROUND A. Statutory Background 19. Under the FDCA and the Hatch-Waxman Act, new drugs may not be introduced into interstate commerce without FDA s approval. See 21 U.S.C. 355(a); see also Actavis Elizabeth LLC v. FDA, 625 F.3d 760, 761 (D.C. Cir. 2010). FDA will not approve a new drug unless the product has been proven safe and effective for each intended use. See 21 U.S.C. 355(d). 20. Section 505 of the FDCA describes three types of applications for FDA approval of a new drug: (1) a new drug application ( NDA ) that contains full reports of investigations of the proposed product s safety and effectiveness, id. 355(b)(1); (2) a Section 505(b)(2) application that contains full reports of investigations of safety and effectiveness but where at least some of the application s information refers to studies that were performed using other drugs and that were not conducted by or for the applicant and for which the applicant has not obtained a right of reference, id. 355(b)(2); and (3) an abbreviated new 7

8 Case 1:14-cv Document 1 Filed 02/27/14 Page 8 of 23 drug application ( ANDA ) that contains information sufficient to show that the proposed product is identical to a previously approved product, id. 355(j). 21. Pioneer drug companies, such as Amarin, that conduct and sponsor research of drug safety and effectiveness devote significant amounts of time and money to developing innovative new products and obtaining FDA s approval of their NDAs. The ANDA process, however, allows generic drug companies to circumvent the onerous requirements for approval of an NDA and to avoid related research and development costs. The Section 505(b)(2) process likewise allows certain drug manufacturers to obtain FDA approval of a new drug based on data developed through research conducted or sponsored by others, including potential competitors. 22. The Hatch-Waxman Act struck a careful balance between promoting competition among brand-name and generic drugs and encouraging innovation. FDA, Abbreviated New Drug Application Regulations; Patent and Exclusivity Provisions, 50,338, 50,338 (Oct. 3, 1994). Specifically, to ensure that competition from generic drug companies would not defeat pioneer drug companies incentives to fund the research and development of new products, Congress enacted various provisions that grant eligible pioneer drugs periods of marketing exclusivity during which FDA may not accept or approve ANDAs or Section 505(b)(2) applications that refer to those drugs. 8

9 Case 1:14-cv Document 1 Filed 02/27/14 Page 9 of At issue in this case is 5-year statutory exclusivity under Sections 505(c)(3)(E)(ii) and 505(j)(5)(F)(ii) of the FDCA, 21 U.S.C. 355(c)(3)(E)(ii), 355(j)(5)(F)(ii). 24. This exclusivity applies to drug[s], no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under [Section 505(b)]. 21 U.S.C. 355(c)(3)(E)(ii), 355(j)(5)(F)(ii). The statute bars the submission of any ANDA (id. 355(j)(5)(F)(ii)) or Section 505(b)(2) application (id. 355(c)(3)(E)(ii)) that refers to an eligible new drug for five years from the date on which the NDA is approved, in this case, July 26, 2017, or four years (here July 26, 2016) if the ANDA or Section 505(b)(2) application certifies that an unexpired patent that claims the drug is invalid or will not be infringed by the manufacture, use, or sale of the proposed product. See id. 355(b)(2)(A)(iv), 355(c)(3)(E)(ii), 355(j)(2)(A)(vii)(IV), 355(j)(5)(F)(ii) In contrast, NDAs that do not qualify for 5-year exclusivity may still be eligible for the lesser protections of new clinical study exclusivity under Sections 505(c)(3)(E)(iii) and 505(j)(5)(F)(iii) of the FDCA. This type of exclusivity applies to an NDA that contains reports of new clinical investigations (other 1 In effect, this statutory exclusivity protects an eligible pioneer drug from generic competition (generally for five years) plus the duration of FDA s review of the ANDA for the generic product. Additionally, new chemical entity exclusivity limits the ability of the pioneer drug company s competitors to challenge its patents for at least four years, and in the event that patent litigation occurs, may prevent FDA s approval of the ANDA or Section 505(b)(2) application from becoming effective until seven and one-half years from the date on which the NDA is approved (here, January 26, 2020). 9

10 Case 1:14-cv Document 1 Filed 02/27/14 Page 10 of 23 than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant. 21 U.S.C. 355(c)(3)(E)(iii), 355(j)(5)(F)(iii). 26. Whereas 5-year statutory exclusivity bars the submission of an AN- DA or Section 505(b)(2) application during the exclusivity period, new clinical study exclusivity postpones only the effective approval of the ANDA or Section 505(b)(2) application, so that the NDA holder potentially faces competition immediately upon the expiration of its new clinical study exclusivity. See id. B. FDA Regulations 27. FDA has promulgated regulations to implement the statutory provisions governing new chemical entity exclusivity. See 21 C.F.R The regulations grant exclusivity to each drug product that contains a new chemical entity. Id (b)(2). 28. Although the statute grants 5-year exclusivity to any drug that contains no active ingredient that has previously been approved by FDA, FDA s regulations define new chemical entity as a drug that contains no active moiety that has been approved by FDA in any other NDA or Section 505(b)(2) application. Id (a) (emphasis added). The regulations thus substitute moiety for the word ingredient in the statute. 29. The regulations go on to define active moiety as the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other 10

11 Case 1:14-cv Document 1 Filed 02/27/14 Page 11 of 23 noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance. Id. C. FDA Precedents on Prior-Approved Mixtures 30. FDA precedents establish that FDA s approval of a mixture as a single active ingredient drug product will not render ineligible for 5-year statutory exclusivity (or, as FDA refers to it, new chemical entity exclusivity) a laterapproved drug product containing a constituent of the mixture. 31. In 1993, FDA recognized new chemical entity exclusivity for Condylox (podofilox) Topical Solution (NDA ). The active ingredient in Condylox, podofilox, is purified from the plant genus podophyullum. FDA had previously approved several other drug products that were mixtures containing podophyllin resin, a cruder extract from the same plant. FDA determined that these prior approvals did not preclude new chemical entity exclusivity for Condylox because these previously approved NDAs did not characterize podofilox as an active ingredient. FDA, Citizen Petition Response, Docket No. FDA-1992-P-0051, at 1 (July 21, 1993). 32. Similarly, in 2009, FDA approved Qutenza (NDA ), a drug whose active ingredient (capsaicin) is a synthetic equivalent of a naturally occurring compound found in chili peppers. FDA recognized new chemical entity exclusivity for Qutenza even though FDA believed that that active ingredient had 11

12 Case 1:14-cv Document 1 Filed 02/27/14 Page 12 of 23 previously been part of the naturally derived mixture (capsicum or cayenne pepper extract) in the previously approved drug product Relevo Liniment. 33. Additionally, FDA has recognized new chemical entity exclusivity for several drug products despite the fact that the active ingredient of each contained constituents also contained in at least one previously-approved drug product. FDA did so with respect to Survanta, approved in 1991; Infasurf, approved in 1998; and Curosurf, approved in In each of these precedents, FDA determined that the prior approval of a mixture containing a constituent also contained in a later-approved product did not preclude new chemical entity exclusivity for the later-approved product. Moreover, FDA opined that Infasurf and Survanta had different active moieties because the active moiety for each product was the entire mixture. See Memorandum from John K. Jenkins to Janet Woodcock re: Addendum to April 22, 1997, memorandum regarding the request by ONY for dispute resolution under 21 CFR related to NDA , at 18 (July 2, 1997) ( Due to the complex nature of the physical interaction of the components that results in the pharmacological activity of naturally derived surfactants, the Division considers the entire mixture to be the active moiety. ). D. The Presumption in Favor of New Chemical Entity Exclusivity. 34. In its 2005 response to a citizen petition filed with respect to the NDA for Vitrase (hyaluronidase) (NDA ), FDA addressed the general question of what exclusivity to grant a drug product if the Agency does not have sufficient information to determine whether a drug contains a previously ap- 12

13 Case 1:14-cv Document 1 Filed 02/27/14 Page 13 of 23 proved active moiety and concluded that [new chemical entity exclusivity] should apply to products about which the Agency has insufficient information to know whether they contain a previously approved active moiety. FDA, Citizen Petition Response, Docket No. FDA-2005-P-0134, at 2 (Oct. 25, 2005). 35. In reaching that conclusion, FDA adopted a presumption for purposes of marketing exclusivity that a product does not contain a previously approved active moiety if the Agency has insufficient information to know if, in fact, it contains one. Id. Application of that presumption, FDA reasoned, promotes pharmaceutical competition without inhibiting innovation, consistent with the objectives of the Hatch-Waxman amendments. Id. at 3. FACTS A. Vascepa 36. Amarin developed and markets the biopharmaceutical product Vascepa (icosapent ethyl) Capsules ( Vascepa ) for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (i.e., triglyceride levels greater than or equal to 500 mg/dl). 37. FDA approved Amarin s NDA for Vascepa (NDA ) on July 26, Vascepa is the first product for which Amarin has secured FDA approval. 38. The active ingredient in Vascepa is icosapent ethyl, an ethyl ester of eicosapentaenoic acid, a type of omega-3 fatty acid. 39. At the time FDA approved Vascepa, the Agency had never before approved a drug with icosapent ethyl as an active ingredient. Indeed, Vascepa 13

14 Case 1:14-cv Document 1 Filed 02/27/14 Page 14 of 23 remains the only pure icosapent ethyl product clinically-proven to significantly reduce triglyceride levels without increasing LDL (low-density lipoprotein) cholesterol levels and to provide a spectrum of additional lipid treatment benefits with a tolerability and safety profile similar to placebo. 40. Amarin devoted significant resources to developing the first FDAapproved icosapent ethyl product with the reasonable expectation that its innovation and investment would be entitled to the protection afforded by new chemical entity exclusivity. 41. Amarin s development program for Vascepa has included numerous investigations, including nonclinical studies; placebo-controlled, randomized, double-blind Phase 3 clinical trials; and a cardiovascular outcomes study. Among the studies conducted by Amarin were two nonclinical carcinogenicity studies that FDA requested on the ground that approval of a new chemical entity for a chronic use indication generally requires that carcinogenicity studies be conducted in two rodent species. B. Lovaza 42. In 2004, FDA approved an NDA filed by Smithkline Beecham for an omega-3 fatty acid product called Lovaza for use in treating elevated triglycerides (NDA ). 43. FDA determined that Lovaza has a single active ingredient and that the single active ingredient is a complex mixture of omega-3-acid ethyl esters. 14

15 Case 1:14-cv Document 1 Filed 02/27/14 Page 15 of GlaxoSmithKline LLC, which currently holds the NDA for Lovaza, has described the active ingredient as the entire fish-oil based mixture in Lovaza not just the ethyl esters of omega-3 fatty acids. 45. Icosapent ethyl is one of the seven known omega-3 acids ethyl esters that are constituents of the complex mixture of omega-3-acid ethyl esters in Lovaza. The other constituents include the ethyl esters of docosahexaenoic acid, docosapentaenoic acid, stearidonic acid, heneicosapentaenoic acid, eicosatetraenoic acid, and alpha-linolenic acid. 46. The presence of icosapent ethyl among the constituents of the complex mixture that is the active ingredient of Lovaza does not, however, render icosapent ethyl an active moiety or active ingredient in Lovaza under applicable FDA precedent. C. Amarin Requests New Chemical Entity Exclusivity For Vascepa. 47. On April 23, 2012, while awaiting FDA approval of its NDA for Vascepa, Amarin requested that FDA recognize new chemical entity exclusivity for Vascepa. 48. On June 22, 2012, representatives of FDA and Amarin met to discuss Amarin s request. 49. FDA took no action on Amarin s request for new chemical entity exclusivity when FDA approved the NDA on July 26, Instead, FDA wrote to Amarin on July 27, 2012, that the Agency had not yet made a final decision as to the new chemical entity status of Vascepa. 15

16 Case 1:14-cv Document 1 Filed 02/27/14 Page 16 of Amarin and FDA subsequently exchanged additional correspondence in which Amarin further explained its position that Agency precedent required FDA to grant new chemical entity exclusivity to Vascepa. 51. Amarin s correspondence with FDA demonstrated that Vascepa is entitled to new chemical entity exclusivity despite FDA s prior approval of Lovaza. Specifically, Amarin showed that, under FDA precedent, see supra paras , prior approval of a drug whose active ingredient is a complex mixture does not render a later-approved drug whose active ingredient is a constituent of that mixture ineligible for new chemical entity exclusivity. 52. Amarin further explained that, in order to be considered an active ingredient in Lovaza, icosapent ethyl would first need to be considered an ingredient. But icosapent ethyl is not listed in the Lovaza label as an ingredient, let alone an active ingredient. 53. Additionally, Amarin noted that icosapent ethyl has not been demonstrated to be responsible for the physiological or pharmacological action of Lovaza, and that a number of clinical differences have been observed between Vascepa and Lovaza. 54. Amarin also pointed out that FDA should apply its presumption in favor of new chemical entity status when there is insufficient data to identify the active constituents of a mixture in a prior-approved drug. As Amarin explained, applying a presumption in favor of new chemical entity exclusivity here would advance the Hatch-Waxman Act s purpose of fostering innovation and be con- 16

17 Case 1:14-cv Document 1 Filed 02/27/14 Page 17 of 23 sistent with FDA s decision to grant new chemical entity exclusivity to Vitrase, see supra paras D. FDA Unlawfully Denies Amarin s Request for New Chemical Entity Exclusivity. 55. On February 21, 2014, FDA issued a decision denying Amarin s request for new chemical entity exclusivity. See Ex FDA agreed with Amarin s argument that Lovaza has a single active ingredient : the omega-3 acid ethyl esters mixture as a whole. Id. at 19; see also id. at Nevertheless, FDA concluded that Lovaza s active ingredient is distinct from its active moiety. See id. at 6 8, In declining to recognize Vascepa s entitlement to 5-year exclusivity, FDA announced a new position that, at least in the context of naturally derived mixtures, even if the entire mixture is the single active ingredient, that active ingredient may contain more than one component active moiety. Id. at Citing studies demonstrating that eicosapentaenoic acid independently lowers serum [triglyceride] levels, id. at 2, FDA concluded that eicosapentaenoic acid meaningfully contributes to and at least in part is responsible for physiological or pharmacological effect of the Lovaza mixture, id. (footnotes omitted) (quoting 21 C.F.R (a)). Thus, according to FDA, eicosapentaenoic acid is at least one of the active moieties of Lovaza. See id. at

18 Case 1:14-cv Document 1 Filed 02/27/14 Page 18 of Because eicosapentaenoic acid is also the sole active moiety of Vascepa, FDA denied Amarin s request for recognition of new chemical entity exclusivity even though Vascepa and Lovaza undisputedly have different active ingredients. See id. 60. FDA did not expressly address Amarin s contention that FDA should apply a presumption in favor of new chemical exclusivity, as FDA has in the past. See supra paras Instead, FDA purported to saddle Amarin with the burden of demonstrat[ing] that [eicosapentaenoic acid] was not an active moiety in any previously approved product, including Lovaza. Ex. 1, at FDA acknowledged that its determination conflicted with several prior Agency precedents. FDA observed, however, that the Agency has not always acted consistently with regard to identification of the active ingredient or active moiety of a naturally derived mixture. Id. at 8; see also id. at 6 ( We acknowledge that the few relevant prior Agency statements and prior actions where FDA considered 5-year [new chemical] exclusivity matters in the context of naturally derived mixtures have not necessarily resulted in consistent outcomes. ); id. at 19 ( [T]he Agency s past actions indicate that FDA has not had a fully consistent practice in this regard. ); id. at 22 ( [P]ast exclusivity determinations have not always been consistent. ). And FDA asserted that several precedents favoring Amarin s position were decided incorrectly. See id. at 10 11, 13 15,

19 Case 1:14-cv Document 1 Filed 02/27/14 Page 19 of FDA did not explain how its new position advances the policies underlying the Hatch-Waxman Act s provisions regarding new chemical entity exclusivity. Rather, FDA disagree[d] with Amarin that the extensive development program that Amarin undertook to gain approval of Vascepa was relevant to Vascepa s eligibility for new chemical entity exclusivity. See id. at 23. FDA apparently failed to recognize that its decision would dilute the statutory incentive for drug manufacturers to develop new products with active ingredients previously unapproved by FDA. E. FDA s Decision Significantly Affects Amarin s Rights to Vascepa. 63. FDA s unlawful denial of Amarin s request for new chemical entity exclusivity exposes Vascepa to the threat of competition from generic manufacturers prior to the date on which Amarin s exclusivity would otherwise allow. Amarin now faces the prospect of imminent patent litigation and potentially a reduced share of the market for triglyceride treatments and a reduced return on its investment in Vascepa. 64. As a result of FDA s decision, Amarin s potential competitors may now file ANDAs or Section 505(b)(2) applications that rely on the safety and efficacy data from the studies that Amarin undertook to support its NDA. 65. Also as a result of FDA s decision, Amarin s potential competitors have acquired the immediate opportunity to litigate the validity and infringement of the Amarin patents that claim Vascepa or uses of Vascepa. 19

20 Case 1:14-cv Document 1 Filed 02/27/14 Page 20 of Amarin seeks declaratory and injunctive relief to secure the exclusivity rights and benefits to which it is entitled under the APA, the Hatch- Waxman Act, and FDA s own prior decisions. CLAIM FOR RELIEF Count I (Administrative Procedure Act: Violation of the FDCA and Applicable Regulations) 67. The above paragraphs are incorporated herein by reference. 68. FDA s denial of Amarin s request for recognition of 5-year statutory exclusivity for Vascepa constitutes final agency action. 69. FDA s final decision on February 21, 2014, to deny Amarin s request for new chemical entity exclusivity for Vascepa is arbitrary, capricious, an abuse of discretion, and not in accordance with law. FDA s action is in violation of the FDCA and the APA. 70. This Court should set aside and vacate FDA s denial of exclusivity; declare that FDA may not accept for filing any ANDA or Section 505(b)(2) application for which Vascepa is the reference-listed drug until after Amarin s 5-year statutory exclusivity expires or the Court so orders; enjoin FDA from accepting any such application before that date; and if FDA accepts any such application before the Court acts, to set aside FDA s acceptance. Count II (Administrative Procedure Act) 71. The above paragraphs are incorporated herein by reference. 20

21 Case 1:14-cv Document 1 Filed 02/27/14 Page 21 of Separate and apart from the unlawfulness of FDA s adoption its new policy that the active ingredient of a naturally derived mixture is not also its active moiety, FDA acted arbitrarily and capriciously in applying its new policy retroactively to Vascepa. 73. FDA s adoption and application of its new policy to Vascepa without notice-and-comment rulemaking was also without observance of procedure required by law. Under FDA s prior application of its regulations, the active moiety in Lovaza would have been considered the undifferentiated mixture, not eicosapentaenoic acid as FDA concluded here. In denying Amarin s request for 5-year exclusivity for Vascepa, FDA impermissibly announced a different interpretation of its regulations without undertaking notice-and-comment rulemaking. 74. Accordingly, this Court should set aside and vacate FDA s denial of exclusivity; declare that FDA may not accept for filing any ANDA or Section 505(b)(2) application for which Vascepa is the reference-listed drug until after Amarin s 5-year statutory exclusivity expires or the Court so orders; enjoin FDA from accepting any such application before that date; and if FDA accepts any such application before the Court acts, to set aside FDA s acceptance. RELIEF REQUESTED WHEREFORE, Amarin requests that this Court issue judgment in its favor and against defendants and issue the following relief: 1. Vacatur of FDA s denial of new chemical entity exclusivity for Vascepa; 21

22 Case 1:14-cv Document 1 Filed 02/27/14 Page 22 of A declaratory judgment that Vascepa is protected by the marketing exclusivity provisions of Sections 505(c)(3)(E)(ii) and 505(j)(5)(F)(ii) of the FDCA; 3. A declaratory judgment that FDA may not accept for filing any AN- DA or Section 505(b)(2) application for which Vascepa is the reference-listed drug until after Amarin s market exclusivity for Vascepa under Sections 505(c)(3)(E)(ii) and 505(j)(5)(F)(ii) expires or the Court so orders; 4. A permanent injunction prohibiting FDA from accepting any ANDA or Section 505(b)(2) application for which Vascepa is the reference-listed drug until after Amarin s market exclusivity for Vascepa under Sections 505(c)(3)(E)(ii) and 505(j)(5)(F)(ii) expires or the Court so orders; 5. A preliminary injunction prohibiting FDA from accepting any ANDA or Section 505(b)(2) application for which Vascepa is the reference-listed drug prior to this Court s determination of the merits of this action; and 6. If necessary, an order setting aside FDA s acceptance of any ANDA or Section 505(b)(2) application that occurs before the time applicable under Sections 505(c)(3)(E)(ii) and 505(j)(5)(F)(ii); and 7. An award of such other and further relief as this Court may deem just and proper. 22

23 Case 1:14-cv Document 1 Filed 02/27/14 Page 23 of 23 Respectfully submitted, February 27, 2014 /s/ Christopher N. Sipes Christopher N. Sipes (D.C. Bar No ) Benjamin C. Block (D.C. Bar No ) Matthew J. Berns (D.C. Bar No ) COVINGTON & BURLING LLP 1201 Pennsylvania Ave., N.W. Washington, DC (202) (Telephone) (202) (Fax) Counsel for Plaintiff Amarin Pharmaceuticals Ireland Limited 23