Takeda Pharm., U.S.A., Inc. v. Burwell

78 F.Supp.3d 65

Takeda Pharmaceuticals, U.S.A., Inc., Plaintiff

v.Sylvia Mathews Burwell, in her official capacity as Secretary, United States Department of Health and Human Services, et al., DefendantsandHikma Pharmaceuticals PLC, et al., Intervenor–Defendants.

and

Elliott Associates, L.P., et al., Plaintiffs

v.Sylvia Mathews Burwell, in her official capacity as Secretary, United States Department of Health and Human Services, et al., DefendantsandHikma Pharmaceuticals PLC, et al., Intervenor–Defendants.

Civil Action No. 14–cv–1668 KBJ

Civil Action No. 14–cv–1850 KBJ

United States District Court, District of Columbia.

Signed January 13, 2015

Jessica L. Ellsworth, Susan Margaret Cook, Catherine E. Stetson, Hogan Lovells US LLP, Matthew D. McGill, Lucas C. Townsend, Mithun Mansinghani, Gibson Dunn & Crutcher LLP, Washington, DC, Michael Sitzman, Gibson, Dunn & Crutcher LLP, San Francisco, CA, for Plaintiff.

Jessica R. Gunder, U.S. Department of Justice, Washington, DC, for Defendant.

UNDER SEAL

MEMORANDUM OPINION

KETANJI BROWN JACKSON, United States District Judge

Table Of Contents

I. BACKGROUND ... ––––

A. Colchicine : A Drug For The Treatment Of Gout ... ––––

B. FDA's Drug Approval Framework: The Hatch–Waxman Amendments ... ––––

1. NDAs, ANDAs, and 505(b)(2) NDAs ... ––––

2. The Patent Certification Requirement ... ––––

3. The Labeling Requirements ... ––––

C. FDA's Approval Of Colcrys (A Colchicine Tablet) ... ––––

1. Mutual Relies On ColBenemid, Published Literature, And Its Own Clinical Studies To Support The Colcrys Application For Acute Flares Of Gout ... ––––

2. Mutual Relies on ColBenemid and Published Literature To Support The Colcrys Application For Prophylactic Treatment of Gout ... ––––

3. FDA Takes Enforcement Action Against Unapproved Oral Colchicine Products Because Their Labels Do Not Reflect The Most Current Data ... ––––

D. FDA's Approval Of Mitigare (A Colchicine Capsule) ... ––––

1. Mutual Files A Citizen Petition Protesting West–Ward's Application And FDA Responds ... ––––

2. FDA Approves Mitigare Capsule For Prophylaxis Of Gout Flares Based On Col–Probenecid, Published Literature, and West–Ward's Own Studies ... ––––

3. West–Ward Launches Mitigare, Alerting Takeda To The Existence Of Mitigare ... ––––

E. Procedural History ... ––––

II. LEGAL STANDARDS ... ––––

III. DISCUSSION ... ––––

A. FDA's Approval Of Mitigare Without A Colcrys Reference And Related Certifications To The Colcrys Patents Did Not Violate The Agency's Rules Or The FDCA ... ––––

1. FDA's Procedural Rules Did Not Require West–Ward To Reference Colcrys Because West–Ward Did Not Rely On Colcrys Data To Support West–Ward's Application For FDA Approval Of Mitigare ... ––––

a. No FDA Policy Establishes That FDA's Reliance—As Opposed To That Of The Section 505(b)(2) Applicant—Gives Rise To Patent Certification Obligations ... ––––

b. Even If Agency Reliance On Third–Party Data Is Relevant, FDA Did Not Approve Mitigare In Reliance On Mutual's Information ... ––––

2. Under FDA's Procedural Rules, An Applicant—Not FDA—Has The Right To Choose The “Most Appropriate” Or “Most Similar” Reference Drug For Its 505(b)(2) Application ... ––––

3. The FDCA Unambiguously Requires A Section 505(b)(2) Applicant To Certify Only To Patents Associated With The Reference Listed Drug ... ––––

B. FDA's Approval Of Mitigare Was Not An Unreasoned Change Of The Agency's Prior Position Regarding Single–Ingredient Oral Colchicine Products ... ––––

C. FDA's Decision To Approve Mitigare With A Label That Contains Safety Information That Differs From Colcrys Was Not Arbitrary And Capricious ... ––––

IV. CONCLUSION ... ––––

The Hatch–Waxman Amendments to the Food, Drug, and Cosmetic Act (“FDCA”), Pub. L. No. 98–417, 98 Stat. 1585 (1984), “balance two competing interests in the pharmaceutical industry: (1) inducing pioneering research and development of new drugs and (2) enabling competitors to bring low-cost, generic copies of those drugs to market.” Janssen Pharmaceutica, N.V. v. Apotex, Inc., 540 F.3d 1353, 1355 (Fed.Cir.2008) (internal quotation marks and citation omitted). Hatch–Waxman achieves this balance, in part, by allowing new applicants for drug approval to rely on research and data that an innovator company generates so long as the new applicant “references” the innovator's drug and “certifies” to the innovator's patents. See infra Part I.B.2; see also 21 U.S.C. § 355(b)(2)(A). Plaintiffs Takeda Pharmaceuticals U.S.A., Inc. (“Takeda”) and Elliott Associates, L.P., Elliott International, L.P., and Knollwood Investments, L.P. (collectively, “Elliott”) allege that the Food and Drug Administration (“FDA”) upset Hatch–Waxman's careful balance when the agency approved an application that Hikma Pharmaceuticals PLC (“Hikma”) submitted through its U.S. agent West–Ward Pharmaceuticals Corp. (“West–Ward”) for a gout medication named Mitigare. Mitigare is a single-ingredient 0.6 milligram (“mg”) oral colchicine drug product that is substantially similar to Plaintiffs' colchicine drug, Colcrys, which FDA approved five years prior to Mitigare based in part on research studies that Takeda's predecessor Mutual Pharmaceutical Company, Inc. (“Mutual”) conducted. In seeking approval for Mitigare, West–Ward neither referenced Colcrys nor certified to the Colcrys patents, and Hikma has now authorized West–Ward to market a generic version of Mitigare that will compete with—and cost less than—Plaintiffs' Colcrys.

In the separate but consolidated complaints that Takeda and Elliott have filed in this Court against Defendants Sylvia Mathews Burwell (in her official capacity as Secretary of the Department of Health and Human Services) and Margaret Hamburg (in her official capacity as head of the FDA), Plaintiffs maintain that FDA's approval of Mitigare without a Colcrys reference or the related patent certifications violates the Administrative Procedure Act (“APA”) because that approval was inconsistent with the agency's procedural rules and the certification provisions of the FDCA. Plaintiffs also claim that FDA's approval of Mitigare was arbitrary and capricious because Mitigare's label lacks certain safety information that is on the Colcrys label—information that is related to Mutual's research and that FDA previously suggested should be on the label of future colchicine drug products. The lawsuits that Takeda and Elliott have filed (and in which Hikma and West–Ward have now intervened) request a stay or rescission of FDA's approval of Mitigare as a remedy for these alleged violations.

Before this Court at present are four cross-motions for summary judgment that the Plaintiffs, the Defendants, and the Defendant–Intervenors have submitted in the context of the two pending actions.¹ This Court has considered these dispositive motions, the oppositions thereto, the supplemental briefing, and the arguments made orally at the two hearings that this Court has held in relation to this matter. Because this Court agrees with Defendants and Defendant–Intervenors that (1) no statute, regulation, or policy required FDA to reject West–Ward's application for Mitigare because the application did not reference Colcrys or certify to the Colcrys patents; (2) FDA's scientific judgment that Mitigare is safe as labeled is well-reasoned and entitled to deference; and (3) FDA did not make an unreasoned change in policy when it approved Mitigare, Takeda's Motion for Summary Judgment in Takeda Pharmaceuticals U.S.A., Inc. v. Burwell, No. 14–1668–KBJ (D.D.C.), is DENIED; Elliott's Motion for Summary Judgment in Elliott Associates, L.P. v. Burwell, No. 14–1850–KBJ (D.D.C.), is DENIED; and Defendants' and Defendant–Intervenors' cross-motions for summary judgment in Elliott Associates, L.P. v. Burwell, No. 14–1850–KBJ (D.D.C.), are GRANTED . This Court issued a separate order consistent with this opinion on January 9, 2015.

I. BACKGROUND

The instant dispute involves two drug products, both of which have the active ingredient colchicine, which is a pharmacological substance that has been used historically for the treatment of gout.² Plaintiffs have a financial interest in Colcrys—an FDA-approved 0.6 mg single-ingredient oral colchicine tablet—and they have brought this challenge to Defendant FDA's recent approval of Intervenors' Mitigare, which is a 0.6 mg single-ingredient oral colchicine capsule. In order to understand the Plaintiffs' challenge fully, some background information about both colchicine itself and FDA's prior approval of Plaintiff's Colcrys, is necessary. The underlying facts are not in dispute.

A. Colchicine : A Drug For The Treatment Of Gout

Doctors have used colchicine—an agent derived from the Colchicum Autumnale plant—to treat gout for centuries. (See Admin. R. (hereinafter, “AR”) at 3 (“The first use of colchicine as a selective treatment for gout is attributed to the Byzantine physician Alexander of Tralles in 6 A.D.”).) Colchicine can be used both for the targeted treatment of gout flares (“acute treatment”) and for longer-term maintenance treatment that is aimed at preventing flares (“prophylaxis”). (See id. at 4, 116–17, 157, 204.) However, there is a relatively small window of doses in which colchicine provides therapeutic benefits without causing severe complications. (See AR at 202.) This “narrow therapeutic index” means that minor dosing changes can have a grave effect on patient outcomes because toxic levels of colchicine can be reached relatively quickly and “can result in serious life-threatening adverse events and death.” (Id.; see also id. at 117 (noting that, although colchicine is therapeutic “at doses of approximately 0.015 mg/kg,” the drug is “toxic in doses greater than 0.1 mg/kg, and typically lethal at doses of approximately 0.8 mg/kg”).) Even doses of colchicine that are within the normal therapeutic range can be toxic if colchicine is used concomitantly with certain other drugs called “CYP3A4 and P-gp inhibitors.” (Id. at 202.)

Consistent with colchicine's long history, drug manufacturers in the...