FDA loss in Vascular Solution off-label promotion case foreshadowed Amarin settlement

Industry and free speech advocates are touting the FDA's concession to drug company Amarin ($AMRN) as a sign that they are winning the battle over the constitutionally of off-label promotion. The settlement was no doubt prodded by a series of legal defeats suffered by the FDA, including not just over the Amarin litigation, but also a recent case involving Vascular Solutions' Vari-Lase device to treat varicose veins.

In February, a jury acquitted Vascular Solutions CEO Howard Root after the Department of Justice accused him of off-label promotion. The case hinged on whether companies can market specific uses based on a general indication, writes Minneapolis-based attorney Kevin Riach of law firm Fredrikson & Byron P.A.

Although the Vari-Lase was cleared by the FDA for the "treatment of varicose veins in the lower extremity," the feds said Vascular Solutions could not legally market the device to treat a specific vein known as the perforator vein, but the jury disagreed.

At a recent hearing on treatments for traumatic brain injury (TBI), the FDA repeated the general principle that general indications cannot be used to make specific claims.

Officials from the device arm (CDRH) said that the broad indications of use for imaging devices like CT and MRI scanners do not enable them to market specific use for quantification of visual biomarkers because "as the intended use becomes more specific, the expectation for the level of evidence increases," in the words of CDRH health scientist Daniel Krainak.

It should be noted that industry did not protest the FDA's stance at the meeting, nor was it mentioned in the context of any court cases. But that just goes to show the far-reaching implications of the Vascular Solutions decision.

And during the case, there were signs of the creeping loss of FDA authority regarding the constitutionality of factual off-label promotion under the First Amendment.

"Notably, the trial court instructed the jury at the opening and close of trial that truthful off-label promotion is not a crime because such speech is protected by the First Amendment. This instruction marks the first time that the First Amendment protection for truthful off-label speech has been adopted by a court outside the Second Circuit, and it is a significant blow to the government's ability to prosecute companies for off-label promotion. The court's instructions are likely to be cited by other companies facing False Claims Act and criminal liability for off-label promotion in future cases," Riach wrote.

But last year's legal victory for Amarin offers an even stronger precedent for drug and device makers.

In particular, attorney Coleen Klasmeier, who heads the food, drug and medical device regulatory practice team at Sidley Austin, previously told FierceMedicalDevices that thanks to the Amarin decision--whose importance was just reinforced by the settlement--drugs and devices that meet a surrogate endpoint will now have to be able to promote themselves off-label with greater confidence, as long as the claims made are true, even if the FDA has doubts about the endpoint's relationship to a clinical outcome or endpoint.

The precedent comes just as the FDA is encouraging the use of surrogate endpoints to accelerated med tech clinical trials, such as those sanctioned under the nascent Expedited Access Pathway for breakthrough devices. 

In another sign of weakness following the unfavorable Amarin ruling in August, the FDA in October unpublished a warning letter related to off-label promotion after the target, Pacira Pharmaceuticals, sued the agency in response. It later settled with the company by agreeing to expand the drug's label. -- Varun Saxena (email | Twitter)

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