{"id":4606,"date":"2015-08-17T01:41:00","date_gmt":"2015-08-17T01:41:00","guid":{"rendered":"https:\/\/www.healthlawpolicymatters.com\/?p=4606"},"modified":"2021-11-03T01:42:25","modified_gmt":"2021-11-03T01:42:25","slug":"first-amendment-protects-truthful-off-label-speech-by-drug-manufacturers-2","status":"publish","type":"post","link":"https:\/\/www.healthlawpolicymatters.com\/2015\/08\/17\/first-amendment-protects-truthful-off-label-speech-by-drug-manufacturers-2\/","title":{"rendered":"First Amendment Protects Truthful Off-Label Speech by Drug Manufacturers"},"content":{"rendered":"\n

Pharmaceutical manufacturers have likely taken note of Amarin Pharma Inc.\u2019s recent success in a pre-enforcement legal challenge against the Food and Drug Administration (FDA or the Agency). On August 7, 2015, Amarin obtained a preliminary injunction that prevents the Agency from bringing misbranding charges against the company for making truthful statements to doctors about off-label (unapproved) uses of the drug Vascepa\u00ae (icosapent ethyl). Amarin claimed that FDA\u2019s threat of initiating a misbranding action had a chilling effect on the company\u2019s ability to engage in constitutionally protected truthful speech, and from providing valuable information to physicians. This\u00a0significant ruling\u00a0<\/a>from Judge Paul Engelmayer in the Southern District of New York represents the first time FDA has been enjoined on First Amendment grounds from prosecuting a drug manufacturer for misbranding based on the manufacturer\u2019s truthful marketing of its product.<\/p>\n\n\n\n

In filing its complaint against FDA, Amarin sought protection for its speech \u201cboth at a general and a statement-specific level.\u201d At a general level, Amarin\u2019s First Amendment challenge alleges that FDA\u2019s threat of misbranding under provisions of the Federal Food, Drug and Cosmetic Act (FFDCA or the Act), 21 U.S.C., \u00a7\u00a7 331(a) and 333(a)(1), restricted Amarin\u2019s speech. Based on\u00a0United States v. Caronia<\/em>\u00a0\u2013 a 2012 decision from the Second Circuit, discussed previously on our blog,\u00a0here<\/a>\u00a0and\u00a0here<\/a>, in which the conviction of a drug company sales representative was vacated because Caronia could not be convicted for on the basis of his truthful speech about off-label uses for a drug \u2013 the court broadly held that Amarin may engage in truthful and non-misleading speech promoting an off-label use of Vascepa, and that this speech may not form that basis of a prosecution for criminal misbranding. At the statement-specific level, the court also reviewed in great detail specific statements and disclosures for which Amarin sought comfort would not be the subject of a misbranding action.<\/p>\n\n\n\n

Although the decision appears to provide some breathing room for manufacturers to make truthful off-label marketing statements under the FFDCA, the Amarin<\/em> court also affirmed FDA\u2019s interests in ensuring the accuracy of information distributed by drug companies, as established by the Supreme Court in the 1980 Central Hudson<\/em> decision. Specifically, governmental restrictions on truthful commercial speech must advance a substantial government interest, and they may not be more extensive than necessary to serve that interest.<\/p>\n\n\n\n

Regulatory Background<\/strong><\/p>\n\n\n\n

Neither the FFDCA nor FDA\u2019s implementing regulations expressly prohibit the promotion or marketing of drugs for an off-label use. But FDA\u2019s longstanding position regarding off-label marketing by drug manufacturers derives from the statutory prohibition against the introduction of any \u201cmisbranded\u201d drug into interstate commerce. The Act establishes that a drug is misbranded if its labeling does not include \u201cadequate directions for use,\u201d and FDA regulations explain that this means directions for use must provide for the safe use of the drug for the purposes for which it is intended the manufacturer or distributor.<\/p>\n\n\n\n

In prosecuting cases involving a misbranding charge that stems from off-label marketing, FDA and the Department of Justice argue that once a manufacturer promotes a drug, whether through oral or written statements, for an unapproved use, such use becomes an \u201cintended\u201d use such that the label no longer accurately conveys \u201cadequate directions for use,\u201d rendering the product misbranded. Over the years, the ban on off-label communications has become broadly applied by the government and has stifled drug company\u2019s engagement with new communication tools, for example social media and other types of electronic communications.<\/p>\n\n\n\n

Factual Background <\/strong><\/p>\n\n\n\n

Amarin\u2019s drug Vescepa (icosapent ethyl) was approved for use in adults with very high levels of triglycerides, and Amarin subsequently sought approval to market Vascepa for a second use, in patients with \u201cpersistently high triglycerides.\u201d Amarin completed a clinical study for this second use, but FDA did not grant approval for the proposed indication, based on the fact that there was uncertainty regarding the impact of the triglyceride reductions in those patients\u2019 cardiovascular risk profiles (notwithstanding that Amarin had met its study objectives and Vascepa produced a statistically significant reduction in those patients\u2019 triglyceride levels). This second use is the off-label use at issue in the case, for which Amarin wanted to make certain objectively truthful statements to doctors, including about the results of the clinical trial conducted in patients with persistently high triglycerides.<\/p>\n\n\n\n

When FDA denied approval of Amarin\u2019s application for the second indication, the letter also stated that Vascepa may be considered misbranded under the FFDCA if it is marketed with a discussion of the study results \u201cbefore approval of this supplemental application\u201d (such warnings about potential violations of the Act are common language in certain Agency communications to drug sponsors). After receiving FDA\u2019s letter, Amarin, along with several physicians, brought an as-applied First Amendment challenge to FDA\u2019s policy prohibiting Amarin \u201cfrom making completely truthful and non-misleading statements about its product to sophisticated healthcare professionals.\u201d<\/p>\n\n\n\n

Amarin\u2019s complaint also contended that FDA\u2019s position deprived the physician co-plaintiffs of important medical information, because physicians may lawfully prescribe drugs for off-label uses and, indeed, in many contexts off-label use may be the standard of care (to the extent that Medicare and other payors may cover payment for such uses). Amarin alleged that physicians \u201cneed truthful and non-misleading information about these drugs to make informed decisions about what is best for their patients,\u201d but FDA\u2019s \u201ccurrent regime for regulating the flow of \u2018off-label\u2019 information. . . severely restricts medical professionals\u2019 access to information from the source most knowledgeable about the drugs: the drug manufacturers.\u201d<\/p>\n\n\n\n

In addition to the broad speech protection that Amarin sought to obtain, the company also sought a ruling permitting it to make specific statements that it alleged were \u201ccarefully-circumscribed, truthful, and scientifically-accurate,\u201d and it provided specific off-label promotional content regarding Vascepa for the court\u2019s review. After filing the complaint, Amarin sought a preliminary injunction to prevent FDA from bringing a misbranding action, with the Agency\u2019s written enforcement threat as a factor weighing in Amarin\u2019s favor.<\/p>\n\n\n\n

Court Grants Preliminary Injunction Request<\/strong><\/p>\n\n\n\n

In his August 7 ruling, District Judge Engelmayer sided with Amarin, explaining that the court\u2019s \u201cconsidered and firm view is that, under Caronia<\/em>, the FDA may not bring such an action based on truthful promotional speech alone, consistent with the First Amendment.\u201d The court held that under Caronia<\/em>, truthful and non-misleading speech promoting the off-label use of an FDA-approved drug cannot be the basis for a misbranding action.<\/p>\n\n\n\n

Next, the court analyzed Amarin\u2019s specific proposed statements about Vascepa, which consisted of three specific statements regarding the second, unapproved use of Vascepa; five disclosures to assure its statements were not misleading; and several scientific reprints that the company proposed to disseminate.<\/p>\n\n\n\n