Amarin Pharma, Inc. v. U.S. Food & Drug Admin.

• Decision Date: 07 August 2015
• Docket Number: No. 15 Civ. 3588(PAE).,15 Civ. 3588(PAE).
• Citation: 119 F.Supp.3d 196
• Parties: AMARIN PHARMA, INC., Dr. Jonathan Herbst, Dr. Eric Rishe, Dr. Peter Gottesfeld, and Dr. Ralph Yung, Plaintiffs, v. UNITED STATES FOOD & DRUG ADMINISTRATION, United States of America, Stephen Ostroff, M.D., and Sylvia Matthews Burwell, Defendants.
• Court: U.S. District Court — Southern District of New York

119 F.Supp.3d 196

AMARIN PHARMA, INC., Dr. Jonathan Herbst, Dr. Eric Rishe, Dr. Peter Gottesfeld, and Dr. Ralph Yung, Plaintiffs,

v.UNITED STATES FOOD & DRUG ADMINISTRATION, United States of America, Stephen Ostroff, M.D., and Sylvia Matthews Burwell, Defendants.

No. 15 Civ. 3588(PAE).

United States District Court, S.D. New York.

Signed Aug. 7, 2015.

Floyd Abrams, Joel Laurence Kurtzberg, Michael Brenner Weiss, Ben Adam Schatz, Shilpa Narayan, Cahill Gordon & Reindel LLP, New York, NY, for Plaintiffs.

Ellen Melissa London, U.S. Attorney Office, New York, NY, Kerala Thie Cowart, Washington, DC, for Defendants.

OPINION & ORDER

PAUL A. ENGELMAYER, District Judge:

In United States v. Caronia, 703 F.3d 149 (2d Cir.2012), the Court of Appeals for the Second Circuit vacated a pharmaceutical sales representative's conviction for conspiring to introduce a misbranded drug into interstate commerce, in violation of 21 U.S.C. §§ 331(a) and 333(a)(1). The conviction was based on Caronia's having promoted a drug for "off-label use," that is, a use other than the one approved by the U.S. Food and Drug Administration (the "FDA"). Caronia's conduct to promote the off-label use, however, had consisted solely of truthful and non-misleading speech. The Second Circuit held that, to avoid infringing the First Amendment, the misbranding provisions of the Federal Food, Drug and Cosmetic Act (the "FDCA") must be construed "as not prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs" where the off-label use itself is lawful. 703 F.3d at 168.

This case grows out of the decision in Caronia and involves the same misbranding provisions. Plaintiff Amarin Pharma, Inc. ("Amarin") manufactures a triglyceride-lowering drug, Vascepa. The FDA has approved Vascepa for one use, but doctors have widely, and lawfully, prescribed it for another. Amarin wishes to make truthful statements to doctors relating to Vascepa's off-label use. The specific statements Amarin seeks to make are derived largely from an FDA-approved study of Vascepa's off-label use, and from writings by the FDA itself on that subject. Amarin therefore contends, and the FDA largely but not wholly concedes, that the statements Amarin seeks to make are truthful and non-misleading. However, the FDA, recognizing that Amarin's purpose in making these statements would be to promote an unapproved use of Vascepa, has threatened to bring misbranding charges against Amarin (and, presumably, its employees) if it does so.

In this action, Amarin claims that the FDA's threat of a misbranding action is chilling it from engaging in constitutionally protected truthful speech. Amarin seeks preliminary relief to ensure its ability to engage in truthful and non-misleading speech free from the threat of a misbranding action. For the reasons that follow, the Court grants such relief.

I. Background¹

Amarin is a biopharmaceutical company incorporated in Delaware and based in New Jersey. Compl. ¶ 24. It and four medical doctors resident in New York² (collectively, "Amarin") bring this suit against the FDA, two officials with responsibility over the FDA (Dr. Stephen Ostroff and Sylvia Matthews Burwell), and the United States (collectively, the "FDA").³ The FDA is the federal agency responsible for approving, disapproving, and otherwise regulating food, drugs, medical devices, and biologies under the FDCA. Id. ¶ 25.

In this background section, the Court first reviews the statutory and regulatory framework under the FDCA governing the sale and marketing of drugs, the provisions relevant to the off-label promotion of drugs, and the FDA's response to date to the Caronia decision addressing the interplay between these provisions and the First Amendment. The Court then reviews the FDA's evaluation of Vascepa and the basis for its decision to not approve it for the off-label use at issue here. The Court then reviews this lawsuit and Amarin's application for preliminary relief.

A. The Statutory and Regulatory Framework

1. Brief History of the FDCA

Before 1938, drug manufacturers could market drugs without premarket approval for safety or effectiveness.⁴ In 1938, a year after more than 100 Americans died after ingesting a toxic drug (elixir sulfanilamide ), Congress enacted the FDCA.⁵

As originally enacted, the FDC A required drugs to be approved for safety, but not for effectiveness, before their introduction into the market. See Drug Industry Act of 1962, S.Rep. No. 87–1744, at 37 (1962), reprinted in 1962 U.S.C.C.A.N. 2884 (reprinted at London Decl., Ex. Z–4, at 8). As a result, even where the evidence did not support a manufacturer's therapeutic claims, the FDA still approved of drugs for general distribution as long as they were shown to be "safe under conditions proposed for their use in the labeling." Id.

This regulatory regime led to a profusion of drug advertising that had "a deliberate intent to mislead." Id.; see also The Drug Industry Antitrust Act of 1962: Hearings before the Antitrust Subcomm. of the H. Comm. on the Judiciary, 87th Cong. 67 (reprinted at London Decl., Ex. AA–1, at 4) ("[T]he physician is bombarded with seductive advertising which fails to tell the truth, the whole truth, and nothing but the truth. This often leads him into prescribing a new drug without adequate warning or information about its possible side effects and, indeed, without any solid clinical evidence that the drug is effective or is even as safe as the advertisers claim."); Waxman, A History, 58 Food & Drug L.J. at 301–02.

In response to rampant false and misleading advertising of drugs, Congress amended the FDCA by enacting the Drug Amendments of 1962. These require manufacturers to demonstrate that their drugs are both safe and effective for their intended uses before they are approved for distribution. Pub.L. No. 87–781, 76 Stat. 780 (1962) ("Kefauver–Harris Amendments"); 21 U.S.C. § 355(a), (d).⁶ Specifically, the FDCA, as amended, provides that: "No person shall introduce or deliver for introduction into interstate commerce any new drug," without the FDA's approval of a "new drug application," which must demonstrate the drug's safety and efficacy through a series of pre-clinical and clinical trials, and must indicate the proposed labeling for the drug. 21 U.S.C. § 355. FDA approval is therefore necessary before a manufacturer can distribute a drug.

2. The Prescription and Use of Approved Drugs for Off–Label Purposes

Significant here, however, the FDA does not regulate doctors. After a drug has been approved by the FDA, a doctor may lawfully prescribe it for both FDA-approved and non-FDA approved ("off-label") uses. See Caronia, 703 F.3d at 153 (citing Buckman Co. v. Plaintiffs' Legal Comm., 531 U.S. 341, 350, 121 S.Ct. 1012, 148 L.Ed.2d 854 (2001) ; Weaver v. Reagen, 886 F.2d 194, 198 (8th Cir.1989) ; John E. Osborn, Can I Tell You the Truth? A Comparative Perspective on Regulating Off–Label Scientific and Medical Information, 10 Yale J. Health Pol'y L. & Ethics 299, 303 (2010) ("Physicians may prescribe FDA-approved drugs ... for any therapeutic use that is appropriate in their medical judgment.")).

The prescription of FDA-approved drugs for off-label purposes is widespread. The most comprehensive study on off-label prescriptions in the United States, conducted in 2001, found that approximately 21% of prescriptions were for off-label purposes. See Randall S. Stafford, Regulating Off–Label Drug Use: Rethinking the Role of the FDA, 358 N. Engl. J. Med. 1427, 1427 (2008).⁷ In certain fields, off- label prescription is the norm rather than the exception. See Euni Lee et al., Off-label prescribing patterns of antidepressants in children and adolescents, 21 Pharmacoepidemiology & Drug Safety 137 (2012) (in 2000–2006 study, more than 90% of antidepressants prescribed to children and adolescents in an outpatient care setting were for off-label purposes); Douglas L. Leslie et al., Off-label use of antipsychotic medication in the department of Veterans Affairs health system, 60 Psychiatric Servs. 1175 (2009) (based on review of Veterans Affairs databases, more than 60% of prescriptions of antipsychotic drugs in 2007 were for off-label use); see also Ishaq Lat et al., Off-label medication use in adult Critical care patients, 26 J. Critical Care 89, 91 (2010) (study of medication orders for 414 patients in 37 intensive care units across nation showed that more than 35% were for an off-label purpose and that 97% of patients received at least one off-label medication).

And the therapeutic—indeed, sometimes life-saving—value of off-label uses of FDA approved drugs has been widely recognized.

In the area of oncology, for example, doctors commonly prescribe drugs for off-label purposes. For a doctor treating a cancer patient, the option of waiting years for possible FDA approval of a new use for an existing drug will often be untenable, and drugs approved by the FDA to treat one type of cancer have proven effective in combatting others, including by reducing tumors or enhancing the effectiveness of chemotherapy.⁸ In 2009, in recognition that certain drugs may be a cancer patient's "last hope," Medicare expanded its coverage of cancer treatment drugs to include drugs not FDA-approved for that purpose. For example, Medicare today covers Gemzar, a drug that the FDA has approved to treat only four types of cancer, to treat a dozen other cancers, including advanced cervical cancer.⁹

In other areas of medicine, too, there are numerous examples in which drugs have been successfully prescribed to treat conditions other than those for which the FDA approved them.¹⁰

A doctor's off-label prescription also may involve using a drug for an approved condition but at an unapproved dosage or directed to an unapproved patient population. For example, many drugs that the FDA has approved for use by adults have not been approved for pediatric use, in some instances because of the challenges presented by testing drugs on infants...