On Friday, a New York Federal Judge ruled that Amarin Pharma is allowed to promote Vascepa, the company’s Omega 3 product used to control triglyceride levels, beyond the currently approved FDA labeling. In the 69-page opinion of this closely-watched case District Court Judge Paul Engelmayer undercut a number of FDA’s arguments seeking to curtail off-label promotion. “Insofar as Amarin seeks preliminary relief recognizing its First Amendment right to be free from a misbranding action based on truthful speech promoting the off-label use of an FDA-approved drug, Amarin has established a substantial likelihood of success on the merits on this point,” the Judge wrote.
Download the District Court Opinion
As background, in 2012, FDA approved Vascepa to treat people with “very” high levels of triglycerides in their blood. Amarin also conducted an FDA-approved study (the “ANCHOR” study) that showed the drug is effective at reducing slightly lower but still “persistently” high levels of triglycerides, which is a common off-label use. Despite the trial successfully meeting its endpoints related to lowering triglycerides, the FDA denied Amarin’s application for approval of this second use. The agency found that recent scientific studies left it unclear whether reducing the triglyceride levels of people with persistently high triglycerides reduces cardiovascular risk. Amarin wanted to disseminate the results of the ANCHOR study and other evidence, with the statement that “supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.”
In its letter to Amarin rejecting the new use, the FDA said it may take legal action if Amarin promoted the drug for that use without approval. Amarin sued to lift the threat of a misbranding suit in May of this year (view the specifics of their complaint) and was granted preliminary relief in Friday’s decision. The ruling follows the 2012 opinion by the U.S. Second Circuit Court of Appeals in United States v. Caronia that vacated a sales rep’s conviction for promoting a drug for off-label use. The Second Circuit has appellate jurisdiction over the New York Court at issue here, and the opinion followed Caronia closely. In doing so, the District Court ordered that:
(1) Amarin may engage in truthful and non-misleading speech promoting the off-label use of Vascepa, i.e., to treat patients with persistently high triglycerides, and under Caronia, such speech may not form the basis of a prosecution for misbranding; and
(2) Based on the information presently known, the combination of statements and disclosures that Amarin proposes to make to doctors relating to the use of Vascepa to treat persons with persistently high triglycerides, as such communications have been modified herein, is truthful and non-misleading.
“The decision opens more direct and effective paths to communicate truthful and non-misleading information about Vascepa clinical trial results and the state of science relevant to the potential of Vascepa to reduce the risk of cardiovascular disease,” stated Amarin regarding the court’s opinion. “With accurate information readily available, healthcare professionals will be better able to assess for themselves how best to choose among available treatment options for their patients. With healthcare professionals better informed, this decision is a victory that Amarin believes will lead to improved patient care.”
What Are Some Takeaways?
The decision “brings to a head over twenty years of wrangling between the industry and the FDA on the applicability of the First Amendment to FDA off-label marketing,” states John Kamp, Executive Director of the Coalition for Healthcare Communication. “Furthermore, it leaves little room for FDA to protect its existing enforcement scheme, and puts all that much more pressure on the agency to provide new policy guidance in the area.” Indeed, FDA has promised to issue new guidance regarding off-label communications of medical products, but has not yet done so.
The court’s decision also “casts doubt on FDA’s long standing rules enabling limited ‘scientific exchange’ with some professionals but banning the promotional communication by the sales force and media marketing,” Kamp adds. FDA has issued a variety of guidance documents severely constricting the “who, what, when, where, and why” of off-label information. For example, while FDA would allow a firm’s medical department to respond to an “unsolicited request” for off-label information, sales personnel have traditionally been cut off from any proactive dissemination of off-label information. However, the court disagreed with this interpretation. The Circuit in Caronia “did not limit that holding to a subset of truthful promotional speech, such as statements responding to doctors’ queries or statements by non-sales personnel.” Judge Engelmayer added astutely: “Indeed, the speech on which the Caronia prosecution itself was based involved the very types of statements promoting off-label use that the FDA most disfavors: proactive oral statements to a doctor by a manufacturer’s sales representative.”
However, Caronia leaves room for prosecuting off-label marketing as misbranding, the court stated, noting first that the First Amendment does not protect false or misleading commercial speech. “Caronia’s construction of the misbranding provisions so to exclude truthful promotion speech affords no protection to a manufacturer that uses false or misleading communications to promote an off-label use,” the Judge wrote. “Second, the First Amendment protects expression, not conduct. A manufacturer that engages in non-communicative activities to promote off-label use cannot use the First Amendment as a shield.” The court also noted that “there is practical wisdom to much of the FDA’s guidance, including that a manufacturer vet and script in advance its statements about a drug’s off-label use.”
The implications of the case are not fully clear at this point. One notable aspect is that while the Second Circuit Caronia decision is only binding on District Courts in New York, Connecticut and Vermont, Amarin is an Irish company with U.S. headquarters in New Jersey. Thus, other companies far and wide could theoretically sue FDA in one of the District Courts with this favorable existing precedent.
Another interesting factor in this case is that dietary supplement manufacturers are permitted to make one of the central claims that Amarin seeks to state, verbatim, on the packaging of their products that are chemically identical to Vascepa. Such packages read: “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.” FDA even noted that it would not object to Vascepa being marketed as a dietary supplement. James Beck, a life sciences attorney at Reed Smith who shed light on the case in an interview, doesn’t really see this fact as having much influence on the magnitude of the case. “If a company is convinced that what it wants to say is truthful, whether there exists another means of saying it is icing on the cake,” Beck stated.
In other words, if the company believes that what it has to say is truthful, FDA is going to be put through a First Amendment defense and the agency will have to come up with a basis to say it is not true. “The fact that FDA is allowing dietary manufacturers to make the same statement undercuts the validity of their argument as to whether it’s not truthful,” Reed states, “but this is more of an evidentiary aspect” rather than any constriction on the scope of the opinion.
This is a potential landmark decision; as such we will continue to add analysis of this case on Policy and Medicine and in-depth on Life Science Compliance Update. The most immediately pressing aspect of the case will be whether the FDA appeals the decision to the Second Circuit. The District Court here on a number of occasions in the opinion was unsympathetic to FDA’s concerns regarding Caronia because they did not seek an appeal. (e.g. “Had the FDA believed that Caronia gravely undermined the drug approval process, it should have sought review of that decision.”) Thus, it will be interesting to see whether FDA changes its course this time around.