The briefing is complete on Amarin’s motion for preliminary injunction.  The parties and several amici have all weighed in, and the court will hear oral argument tomorrow.

To this point, there has been significant back and forth between the FDA and Amarin.  Here is some of it.  The FDA argued that it mooted much of Amarin’s preliminary injunction request by sending its June 5 letter to Amarin.  We all saw that argument coming. Even though Amarin never asked for an FDA response to its proposed off-label promotion, it got one anyway.  In the June 5 letter, the FDA said that it “does not have concerns with much of the information [that Amarin] proposed to communicate.”  The FDA’s decision to send this unsolicited response appeared litigation driven and, unsurprisingly, it led off the FDA’s response brief:

The June 5 Letter makes clear that FDA does not object to Amarin’s distribution of summaries and reprints of the ANCHOR trial and journal article reprints, if Amarin takes the reasonable steps outlined in the Letter and ensures that such dissemination is truthful and non-misleading. June 5 Letter at 10.  Assuming Amarin takes those steps, then for all but one of the communications proposed in the Complaint, FDA would not rely on such communications in an enforcement action against Amarin.

(FDA Br. at 15.)

Amarin saw it quite differently, arguing in its reply brief that the June 5 letter clarified that the FDA has every intent on criminally prosecuting
Amarin if it has a full and truthful dialogue with health care providers on off-label uses of Vascepa:

[T]he Complaint states—in the most straightforward manner—that Amarin not only wishes to communicate with healthcare professionals “through written materials and digital media about its product” but also to “proactively engag[e] in a dialogue with doctors and other healthcare professionals about Vascepa®” in a truthful and non-misleading manner.

Nothing in FDA’s June 5 letter to Amarin or in its brief to this Court recognizes the company’s First Amendment right to do or say any of these things.  The letter contemplates no such dialogues or discussions at all, but only academic presentations in what FDA refers to as educational or scientific settings.  . . .  Neither FDA’s letter nor its brief acknowledges the right of Amarin’s representatives to seek to promote Vascepa®, truthfully and in a non-misleading manner, to doctors in their offices.  In fact, it is now clear (if there were any previous doubt about it) that such activities could subject Amarin to significant risk of criminal prosecution.  FDA’s brief to this Court is unambiguous that any dissemination of “the reprints and summaries about unapproved uses in a manner not described in the June 5 letter” may be considered by FDA “as evidence of intended use,” and thus potentially criminal.  And FDA asserts that only if the “journal reprints and summaries of the ANCHOR trial results” are disseminated in the particular manner set forth in its June 5 letter—which says not a word about dialogue or discussions, let alone meetings in which Amarin sales representatives proactively discuss Vascepa®—would Amarin be free of significant risk.

(Amarin Reply Br.at 2-3.)

Underlying the parties’ different understandings of the effect of the letter is the FDA’s continuing argument that it does not prohibit off-label speech but rather uses it as evidence that a manufacturer is marketing a drug for an unapproved use:

[T]he role of truthful speech regarding unapproved uses is strictly an evidentiary one. . . . Under the FDCA a manufacturer’s intended uses for a drug “may be derived or inferred from labeling, promotional material, advertising, and ‘any other relevant source.’”  Nat’l Nutritional Foods, 557 F.2d at 334.  Thus, when a manufacturer engages in speech regarding an unapproved use, such speech is potentially relevant to determining whether the unapproved use is an intended one, with the regulatory consequences for the distribution of the drug that flow from such a determination.

(FDA Br. at 20.)

If this argument seems familiar, it is.  The same government made the same argument on the same issue in Caronia—and lost.  To read the FDA’s brief, though, you’d come away with the impression that Amarin is facing an entirely different government and regulatory regime than those that were scrutinized in Caronia less than two years ago:

[T]he outcome in Caronia is not controlling.  Caronia did not involve speech that was shown at trial to be potentially false or misleading and did not involve the use of speech as evidence of intent.  Instead, it involved the constitutionality of a ‘complete and criminal ban on off-label promotion.’  703 F.3d at 167.

(FDA Br. at 25.)

If there has been a sea change in the FDA’s regulation of off-label promotion in the last year-and-a-half, we’re not aware of one.  Put another way, the FDA seems to be arguing that a different regulatory regime was at issue in Caronia, one created only for the purpose of that litigation, and that, here, Amarin is facing the real regulatory regime.  This seems a bit odd.  More important, it highlights the longstanding difficulty in predicting or articulating the FDA’s regulation of off-label promotion.

The FDA’s “speech as evidence” argument doesn’t fare well when subjected to real scrutiny.  No matter how argued, this notion runs up against the reality that it involves a regulatory regime that bases criminal liability, in many instances, solely on truthful, non-misleading speech.  In Caronia, the off-label promotion was the sole act that constituted the criminal violation.  The same would be true here if the FDA were to prosecute Amarin for the type of off-label promotion proposed in its complaint.  The speech results in the prosecution and, unless the FDA adopts a new regulatory approach, it always will.

Amarin’s reply brief pointed out the tautology of the government’s “speech as evidence” argument:

This speech-as-evidence argument is, on its face, a charade.  By definition, a drug company’s promotion of its product for off-label use is, in and of itself, a reflection of its intent that its drug be used off-label.  The promotion— the speech—is the illegal act.  The government’s speech-as-evidence tautology with respect to off-label promotion has not been lost on commentators or courts.  Professor Smolla explains:

The FDA and its prosecutors invoke a . . . circularity.  There is nothing illegal about promoting off-label drug uses.  But there’s a catch (there’s always a catch).  No drug may be promoted if it is misbranded.  Any drug promoted for use other than a use approved by the FDA (i.e., any drug promoted for an off-label use) is, by definition, “misbranded.”  And much like the military in Catch-22, which claims it is not penalizing the pilot merely for asking to be grounded, but rather is simply using “the ask” as evidence of the pilot’s sanity, the FDA claims it is not penalizing the promoter of off-label uses for the promotion itself, but rather as evidence of misbranding.  While seductively clever, the government’s argument is too clever by half.  Here is its flaw: the . . . evidentiary-use principle is valid only when the elements of the underlying crime or tort do not themselves require expressive activity. In such cases it is possible to coherently separate the use of speech as evidence of a nonspeech element from the imposition of liability for the speech itself.  When expressive activity is a necessary element of the crime or tort, however, no such separation is possible. . . .  Unlike the racially motivated beating in [Wisconsin v.] Mitchell, [508 U.S. 476 (1993),] conduct that was not intrinsically linked to expression at all, it is impossible to conceive of a prosecution for the introduction of a misbranded drug into interstate commerce predicated on the promotion of the drug’s off-label uses without making the expressive promotion of the off-label use an element of the crime.

(Amarin Reply Br.at 5-6.)

Finally, the FDA argued that its off-label regulatory regime is narrowly tailored to the governmental interest of promoting safe and effective drugs.  (FDA Br. at 38-42.)  In doing so, the FDA spent more time taking down alternative regulator regimes than it did supporting its current regulation of off-label promotion, a regime that still isn’t entirely clear.  As part of this discussion, the FDA rejected all the alternative regulatory regimes suggested (non-exclusively) by the Caronia court:

In discharging its regulatory responsibilities, however, FDA has reviewed other alternatives—including all of those identified in Caronia, 703 F.3d at 168—but has found them all inadequate to meet public health needs, and therefore not viable less restrictive alternatives to the regulatory approach adopted by FDA.

(FDA Br. at 38.)

But do these litigation-driven conclusions really discharge the FDA’s regulatory responsibilities?  As Amarin argued in its reply brief, the say-so of one of the FDA’s senior officials does not establish that the FDA’s off-label regulations are so narrowly tailored as to satisfy the First Amendment:

Caronia concluded that “numerous” alternatives are available to the government and on that basis held that the government’s off-label promotion ban failed Central Hudson’s fourth prong.  The government now revisits these alternatives and—unsurprisingly—has “found them all inadequate.”

In support of that conclusion, the government has submitted a declaration from Dr. Janet Woodcock, with respect to the “numerous” Caronia alternatives.  Dr. Woodcock devotes a single paragraph (in one instance, two paragraphs) to each.  She makes no representations that FDA has explored these alternatives beyond the context of this litigation (which has been pending for less than two months), or who at FDA had input in any such considerations or authority over the conclusions reached.  She does not cite in her Declaration, or attach to it, any documentary evidence to support her conclusions. Once, she references—but does not provide or cite to—“studies” (id. ¶ 49) in support of a conclusion as to one alternative. . . . Indeed, she cites no concrete factual information at all in addressing the Caronia alternatives other than two brief anecdotes about specific drugs. Woodcock Decl. ¶ 47. She speculates as to certain outcomes, stating that they “would likely” (id. ¶¶ 43, 52); “may” (id. ¶ 44); or “could” (id. ¶ 49) occur.

(Amarin Reply Br.at 8-9.)

The briefing hits on more issues than this, particularly a break-down of the Central Hudson First Amendment analysis.

But tomorrow the litigation moves from briefing to oral argument.  That should be fascinating.  The case is pending in the Southern District of New York, part of the Second Circuit. And so the FDA will be arguing in the very circuit that issued Caronia to marginalize its holding and reject its regulatory suggestions.  Somewhere along the line, either before the trial court or on appeal before the Second Circuit, that rubber is going to meet the road.