Off-label marketing regulations and enforcement

Off-label marketing regulations and enforcement Implications of the Caronia and Amarin rulings

Norton Rose Fulbright US LLP Wednesday, September 16, 2015

Off-label marketing regulations and enforcement Implications of the Caronia and Amarin rulings

Speaker Saul Perloff

Partner Norton Rose Fulbright US LLP

San Antonio

Speaker Robin Adelstein


New York

Moderator Cori Goldberg

Senior Associate Norton Rose Fulbright US LLP

New York

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Administrative Information

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Off-label marketing regulations and enforcement

Off-label marketing regulations and enforcement

Background Although physicians are free to prescribe drugs for any indication that meets the appropriate medical standard of care, the government prosecutes manufacturers for off-label marketing using two vehicles:

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Food, Drug, & Cosmetic Act (FDCA) Although the FDCA’s misbranding provisions do not expressly prohibit the marketing or promotion of drugs for off-label use, prosecutors have used them to bring criminal actions against manufacturers that make assertions inconsistent with their products’ approved drug labels.

Federal False Claims Act (FCA) A manufacturer may be civilly liable under the FCA for making a false statement about a drug that causes the off-label prescription of that drug for an unapproved use that is not reimbursable by federal healthcare programs.

FDCA Misbranding Provisions

21 U.S.C. § 355(a)

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Requires that before drugs are distributed into interstate commerce, they must be approved by the FDA for specific uses


FDCA Misbranding Provisions 21 U.S.C. § 331 (a)

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Prohibits distributing misbranded product



21 U.S.C. § 352

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Declares a drug or device “misbranded” if its labeling fails to bear “adequate directions for use”


21 C.F.R. § 201.5 defines “adequate directions for use” as

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“directions under which the layman can use a drug safely and for the purposes for which it is intended.”

FDCA Misbranding Provisions 21 C.F.R. § 201.128 defines “intended use” as

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“the objective intent of the persons legally responsible for the labeling of drugs”

“the circumstances that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised.”

which may be demonstrated by

“such persons’ expressions or may be shown by the circumstances surrounding the distribution of the article,” including “oral or written statements by such persons or their representatives”

and

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31 U.S.C. §§ 3729 et seq. prohibits

FCA Provisions and Enforcement

a person from knowingly presenting or causing to be presented a false or fraudulent claim to the government for payment or approval

Penalties for violation include: ‒ Civil penalties $5,500-11,000 ‒ Treble damages ‒ Exclusion from federal healthcare

programs

and

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FCA underlying theory

FCA Provisions and Enforcement

Manufacturers who have knowingly engaged in the off-label promotion of their prescription drug or medical device products, and have received payments from Medicare or Medicaid as a result of such off-label promotion, have committed a fraud upon the government and are accordingly punishable under the FCA.

Sorrell vs. IMS Health, Inc., 131 S. Ct. 2653 (2011)

Supreme Court struck down as unconstitutional Vermont’s attempts to restrict the use of physician prescribing data by pharmaceutical companies for marketing purposes, holding

“Speech in aid of pharmaceutical marketing … is a form of expression protected by the Free Speech Clause of the First Amendment.”

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U.S. v. Caronia Docket No. 09-5006-cr (2d Cir. 2012)

Off-label marketing and free speech Jazz Pharma sales representative (Caronia) informed doctors of studies establishing Xyrem®’s efficacy for unapproved uses and in unapproved sub-populations.

Caronia was convicted of conspiracy to misbrand based on truthful statements of off-label use.

2d Circuit reversed holding that the First Amendment forbids the government from prosecuting pharmaceutical manufacturers and their reps for truthful speech promoting the lawful, off-label use of an FDA-approved drug.

Basis of appeal was improper jury instruction in which the law was explained to forbid off-label marketing and the prosecution centered around Caronia’s speech rather than his intent to misbrand.

FDA did not appeal and interpreted the ruling narrowly.

Amarin Pharma, Inc. et al. v. FDA, et al., Case No. 1:15-cv-3588 (S.D. N.Y. Aug. 7, 2015)

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Amarin manufactures Vascepa®, an FDA approved drug consisting only of pure EPA indicated to reduce triglyceride levels in adults with very high triglyceride levels.

Amarin pursued approval of Vascepa® to treat patients with high triglyceride levels pursuant to the FDA’s Special Protocol Assessment (SPA) program.

Despite having met all clinical endpoints, the FDA rescinded the SPA agreement and refused to approve Vascepa® for the new indication.

Amarin Pharma, Inc. et al. v. FDA, et al. Case No. 1:15-cv-3588 (S.D. N.Y. Aug. 7, 2015)

Judge Engelmayer granted Amarin’s motion for preliminary injunction, ruling that Amarin can make truthful and non-misleading statements promoting Vascepa®’s potential benefits for patients with persistently high triglycerides without fear of prosecution.

“The Court’s considered and firm view is that, under Caronia, the FDA may not bring such an action based on truthful promotional speech alone, consistent with the First Amendment . . . Where the speech at issue consists of truthful and non-misleading speech promoting the off-label use of an FDA-approved drug, such speech, under Caronia, cannot be the act upon which an action for misbranding is based.”

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Current Status of Amarin Pharma, Inc. et al. v. FDA, et al.

Possibility of settlement looms

August 28, 2015 letter from Amarin to the Court

August 31, 2015, the Court stayed the Amarin proceedings until October 30, 2015

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“[t]he parties have agreed to explore the possibility of settlement in this matter.”

requested that further proceedings be stayed until October 30, 2015, “on which date the parties will file a joint letter advising the Court of their views as to next steps in the case.”

Scope of the Ruling

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Does the reasoning extend beyond the criminal context?

What is the scope of the Amarin ruling?

‒ How does this impact FCA cases? ‒ Other civil actions?

Is the ruling limited to pharmaceuticals?

‒ What about foods & dietary supplements? ‒ Medical devices? ‒ OTC drugs?

How much did the safety profile of Vascepa® influence the outcome?

Practical considerations after Amarin

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Practical Considerations

What makes marketing

claims truthful and not

misleading?

Who decides?

‒ In what context does it get decided?

‒ Is there a difference between proactive promotional statements v. responses to unsolicited requests?

Who carries the burden of

proof?

Will FDA’s new guidance

(when issued) make a

difference?

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Practical Considerations

How do you mitigate your company’s

risks?

How do you balance

reputational risk and expense v.

benefits of such promotion?

Is this a slippery slope?

Are there other, hidden

risks?

Appendix

Current status of FDA rulemaking on off-label promotion

2011 2015 2011 2012 2013 2014 2015

2011 & 2013 Citizen petitions request greater clarity for manufacturers to provide “truthful and non-misleading scientific information” regarding drug and device uses beyond those approved by the FDA

Dec. 2011 FDA issues Draft Guidance: “Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices”

Feb. 2014 FDA issues Draft Guidance: “Distributing Scientific and Medical Publications on Unapproved New Uses – Recommended Practices”

June 2014 FDA announces it will issue draft guidance concerning the dissemination of off-label information on medicines

May 2015 FDA announces public meeting on off-label promotion restrictions in “summer” 2015 (TBD)

July 2015 House passes 21st Century Cures Act that would expand scientific information that manufacturers can share with payers, formulary committees or “similar entities”

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Questions and wrap-up


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Please direct any questions regarding the administration of this presentation to Cristina De Los Santos at [email protected].

Continuing Education Information

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Speaker Bios

Cori Annapolen Goldberg focuses her practice on FDA issues for the food, drug, and device industries; health law matters; government and internal investigations; and white collar criminal defense. Cori has both transactional and regulatory expertise. She has worked with clients including medical device manufacturers, pharmaceutical companies, food manufacturers, hospitals, academic medical centers, physicians, and other health care providers. Her practice includes the representation of clients in compliance matters, including internal investigations and self-disclosures. She also advises clients on issues related to accreditation by the Accreditation Council for Graduate Medical Education (ACGME) and the Liaison Committee on Medical Education (LCME).

Cori advises her clients on a broad array of topics including food and drug law issues, clinical research considerations, corporate compliance concerns, and fraud and abuse issues. She also represents large corporations in investigations by the US Department of Justice, the Department of Health and Human Services Office of Inspector General, the US Securities and Exchange Commission, and other federal and state agencies.

Prior to joining, Cori served as a judicial law clerk to Judge Clayton Greene, Jr. on the Court of Appeals of Maryland.

Moderator Cori Goldberg

Senior Associate Norton Rose Fulbright US LLP

New York

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Speaker Bios

Speaker Robin Adelstein


New York

Robin Adelstein's pragmatic approach to the practice of law is informed by her experience, having served as in-house counsel at Swiss healthcare company Novartis and UK alcohol beverage leader Diageo before becoming North American General Counsel of Sandoz, the generics division of Novartis.

Whether involving pharmaceuticals or consumer products, Robin has advised her clients on a wide range of issues and directed material litigation and government investigations to positive results. As a former General Counsel of a multibillion-dollar company, Robin knows first-hand the importance of providing prompt, accurate and practical advice on legal and compliance issues, particularly in the context of balancing complex business objectives. Robin also understands the challenges with managing outside counsel, having redesigned and run the Novartis Preferred Firm Program globally.

Robin litigates complex, commercial disputes, class actions and multi-jurisdictional cases before US federal and state courts, and represents clients in government enforcement actions by the Federal Trade Commission and Department of Justice, as well as the HHS Office of the Inspector General. She has defended clients in qui tam matters in many locales and in investigations and litigation by numerous State Attorneys General. Robin also advises companies with respect to the antitrust issues arising in mergers and acquisitions, joint ventures, trade association activities, distribution practices, pricing programs and other aspects of competitor and customer communications and associations.

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Speaker Bios

As a partner in the Intellectual Property Group and the head of the advertising practice, Saul Perloff represents domestic and international clients in a wide range of complex advertising and unfair competition disputes under the Lanham Act and state law. He also counsels and advises pharmaceutical, consumer product, biotechnology and other clients on advertising and brand protection strategies.

Saul has successfully prosecuted and defended disputes involving false advertising, unfair competition and trademark/trade dress and patent infringement in fifteen states across the country. In addition to his advertising and brand protection practice, Saul has represented companies in cases involving securities fraud, anti-trust and professional liability. He also represents clients in internal investigations of accounting fraud and irregularities.

From 1992 to 1995, he served as a trial attorney and member of the Chief Counsel's Honor Program in the US Army Corps of Engineers.

Speaker Saul Perloff


San Antonio

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Law around the world

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Documents

Off-label marketing regulations and enforcement