Say goodbye to the FDA’s off-label marketing prohibition as we know it. A federal judge put another nail into the off-label marketing coffin on August 7, 2015 when he said the FDA’s rule prohibits free speech.
This was the second nail. The first nail came in 2012, when a drug sale rep’s conviction of violating the misbranding rule was tossed out by a federal appeals court in the Caronia case for the same reason.
“Congress Shall Make No Law”
Here’s what the Constitution says in the First Amendment about free speech: “Congress shall make no law…abridging the freedom of speech….” It’s simple and elegant. No law. Period.
There is no exception for the FDA, yet the FDA abridges speech when it chills the right of device and drug makers by mandating that they can only speak about on-label information. On-label information the FDA has approved.
This second case began when four physicians, Jonathan Herbst, Eric Rishe, Peter Gottesfeld and Ralph Yung and a fish oil maker, Amarin Pharma, Inc. sued the FDA in federal court to secure their rights to provide and receive truthful information, even if that information wasn’t on the FDA-approved label.
Paul A. Engelmayer, a U.S. district court judge in New York (and former Wall Street Journal reporter), agreed with the physicians and company.
In a 71-page opinion, Judge Engelmayer cited the 2012 Caronia decision by an appeals court which threw out the conviction of a drug rep, who had shared truthful, but off-label information with physicians. That court held that the FDA cannot “prohibit and criminalize truthful off-label promotion of FDA-approved drugs.”
But the Caronia decision wasn’t enough for the FDA. The agency argued that Caronia only applied to one special case and continued to threaten to make criminals of anyone else trying to push truthful off-label speech.
Amarin makes Vascepa, a tryglyceride-lowering drug (fish oil). The FDA approved it for one use, but physicians widely prescribed it for another use. Amarin wanted to make truthful statements to physicians about that off-label use. The FDA did not challenge the truthfulness of Amarin’s off-label information. However, the FDA threatened to bring misbranding charges against the company if it distributed the information.
Amarin went to court and asked the federal judge to issue an injunction to keep the FDA from making them criminals. The court granted their request.
FDA Safety and Effectiveness Authority History
A little history about the FDA’s authority is helpful.
Prior to 1938 companies could market products without FDA approval. Then 100 people died after ingesting elixir sulfanilamide and Congress passed the Federal Food, Drug, and Cosmetic Act (FDCA). Approval was needed for safety, but not effectiveness. This led to some manufacturers deliberately misleading the public and physicians about the effectiveness of their product. So Congress amended the FDCA in 1962 to require a demonstration of safety AND effectiveness and that the FDA must approve the product before it can be distributed.
Off-Label As Standard of Care
But the FDA doesn’t regulate physicians and after a product is approved, physicians can use it any way they see fit. By 2001, approximately 21% of prescriptions were for off-label purposes. In some cases it became the norm. The therapeutic value of off-label use became widely recognized.
In 2009, the FDA acknowledged that off-label uses “may even constitute a medically recognized standard of care.”
Misbranding, False Claims and Off-Label
The FDCA does not expressly prohibit the promotion of products for off-label use, but the FDA applies a “misbranding” criminal charge if someone promotes off-label. Punishment can result in a one year prison term and a $1, 000 fine. If it’s shown that you intended to mislead, then you can go prison for three years and face a $10, 000 fine. Companies found guilty of off-label promotion also face civil and federal suits under the False Claims Act.
It’s not an idle threat. In recent years federal prosecutors, according to the court, have “actively” pursued criminal misbranding charges against companies and sales reps. In 2012, GlaxoSmithKline pled guilty to misbranding and paid a $1 billion fine. The same year, Abbott Laboratories, Inc. paid a $500 million fine. In 2010 Allergan Inc. paid a $375 million fine.
When the manufacturers’ “speech” is untrue or misleading, the FDA says the public’s health in endangered. But generally speaking, the FDA says its goal in pursuing criminal charges is to encourage the use of the agency’s approval process.
The FDA has allowed some off-label educational activity by manufacturers by issuing draft guidances on how manufacturers should respond to unsolicited requests for off-label information. The manufacturer should disseminate truthful and non-misleading information only to that person and tailored to answer only the requester’s specific question.
Before Caronia, no one had challenged the FDA’s application of the misbranding provision of truthful and non-misleading promotional statements.
FDA Challenges Begin
In the 1998 Friedman case, a public interest group challenged the FDA over the prohibition of distribution of textbook excerpts and article reprints from medical and journals. The court rejected the FDA’s argument that those commercial communications were illegal. The FDA appealed. Perhaps fearing a loss, the agency pulled the appeal and adopted a much narrower construction of the guidance document.
Then in 2012 came Caronia and the appeals court said “that a manufacturer’s speech promoting off-label use is constitutionally protected commercial speech, and that the First Amendment places limits on a misbranding prosecution to the extent it is based on the truthful promotion of FDA-approved drugs for off-label use.”
But the FDA chose to read Caronia “narrowly” and said the decision preserved their right to bring misbranding actions.
In February 2014, the agency issued an updated draft guidance regarding the dissemination of scientific or medical journal articles under certain conditions. The guidance said that if a sales representative characterizes an article to suggest that a drug is safe or effective for an unapproved use, the agency may use such speech as evidence that the manufacturer intended to promote that use.
Then in June 2014, the agency agreed to conduct a comprehensive review and issue a new guidance within a year. That promised guidance had not been issued at the time of Amarin’s lawsuit. On July 7, 2015, the agency declined to tell the court when the new guidance would be offered.
Amarin’s Legal Challenge
Amarin sought FDA approval for two separate uses of Vascepa. The company received FDA approval on September 25, 2011 to market Vascepa for treating adult patients with triglyceride levels above 500 mg/dL of blood (“severe hypertriglyceridemia, ” or “very high triglycerides”). The second request was for patients with triglyceride levels between 200 and 499 mg/dL of blood and who are already on statin therapy (“persistently high triglycerides”).
The second request was the off-label use at issue in this case.
After failing to receive FDA approval for the second use and being threatened with misbranding prosecution, the company and the four physicians filed suit in May 7, 2015.
The physicians argued that they needed truthful and non-misleading information to make informed decisions about what’s best for their patients. They argued that the FDA’s current method for regulating the flow of off-label information “severely restricts” medical professionals’ access to information from the source most knowledgeable about the product.
FDA Responds
In June 2015, the FDA tried to narrow the dispute of some of Amarin’s communications by noting that “some fall within the scope” of existing allowed claims. The FDA tried to make Amarin’s suit irrelevant by offering to define some conditions under which the company could communicate to physicians about some of the information in question.
The agency reiterated that it was reviewing its regulations over dissemination of information and a new guidance would be forthcoming.
Amarin could have declared victory and gone home at that point. But the company pressed on.
On June 23, 2015, the FDA opposed Amarin’s request for preliminary relief. The agency told the court that if the company accepted its proposal, the controversy would be moot. If Amarin didn’t agree to the agency’s proposal to modify some statements, then Amarin’s plan was a “frontal assault…on the entire approval framework.”
On June 30, the company told the agency it wasn’t interested in their proposal and the agency’s threat to prosecute the company as an attempt to “refight old, lost battles.”
On July 7, 2015, the court heard the arguments.
Judge’s Ruling and Aftermath
The judge said 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. A fair reading of that decision refutes the FDA’s view that the Second Circuit’s ruling was limited to the facts of Caronia’s particular case.”
Jude Engelmayer ruled that Amarin had established a “substantial likelihood of success on the merits on this point, ” and granted the injunction. He noted that misbranding is “unlike the crimes of jury tampering, blackmail, and insider trading to which the FDA has analogized, in which ‘the speech is the act’.”
So now what?
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, ” John Kamp, executive director of the Coalition for Healthcare Communication told John Sullivan of Policy and Medicine. “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.”
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.
The case is the “first decision that clearly and unequivocally rebuffs the government’s view that off-label promotion can be prosecuted even if it is truthful and non-misleading, ” Floyd Abrams, a partner at Cahill Gordon & Reindel and Amarin’s counsel, said during a call with reporters after the ruling.
Warning to Manufacturers
But before manufacturers turn their sales reps loose on physicians with truthful yet off-label information, consider that the judge said there were limitations and gave some advice to manufacturers when he said:
“Although the FDA cannot require a manufacturer to choreograph its truthful promotional speech to conform to the agency’s specifications, 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. A manufacturer that leaves its sales force at liberty to converse unscripted with doctors about off-label use of an approved drug invites a misbranding action if false or misleading (e.g., one-sided or incomplete) representations result. Caronia leaves the FDA free to act against such lapses.”
The FDA has 60 days after the ruling to appeal.
