The tricky part about the off-label marketing of drugs, or the marketing of drugs to doctors for unapproved indications, is that companies, and not the US Food and Drug Administration (FDA), may get to decide what some courts are referring to as “truthful and non-misleading” marketing information.

Republican Reps. Fred Upton (MI) and Joe Pitts (PA) on Thursday took FDA to task for the agency’s “inability or unwillingness to publicly clarify its current thinking” on off-label marketing, particularly as courts in recent months have ruled against FDA and said drug and device companies are allowed to disseminate this kind of marketing information as it’s protected by the First Amendment.

At face value, the letter would make it seem like FDA is woefully behind in adapting to the shifting legal landscape, or as the representatives put it, using settlement agreements as the “only means by which policy is formulated.” But a look into the three recent court decisions on off-label marketing reveals a murky line between promoting unproven uses of medical products, or even claims for uses rejected by FDA, and providing doctors with pertinent information to help them decide what to prescribe.

Court Cases

The letter cites a number of recent court victories over FDA, including with Pacira Pharmaceuticals’ off-label claims for its injectable local anesthetic, Amarin’s claims regarding its triglyceride-lowering cholesterol drug and Vascular Solutions’ laser treatment.

However, in all three cases, FDA was overruled not because of new data that would further substantiate why these companies should be able to market their health products for off-label conditions.

On the Pacira front, FDA sent the company a warning letter in 2014 over concerns that the injectable local anesthetic Exparel, which is approved for use in two specific surgeries: bunionectomy and hemorrhoidectomy, was being used in other surgical settings, such as in a laparoscopic cholecystectomy and an open colectomy, and neither surgical procedure is supported by data, FDA said.

FDA also said it was "concerned" about an "array of professionally directed promotional materials" that implied the drug to be safe and effective in "various other surgical procedures."

The two sides in December 2015 settled the matter and FDA approved a change to the drug’s label to include new indications.

With Amarin, however, the US District Court for the Southern District of New York ruled that the statements the company proposed to make to doctors for Vascepa (icosapent ethyl), as a treatment of persistently high triglycerides, are “truthful and non-misleading,” despite being indications that FDA rejected the drug for.

Similarly, Vascular Solutions encouraged salespeople to market its Vari-Lase laser treatment as targeting perforator veins, even though FDA refused to approve it for that use.

GOP Proposal

Pitts and Upton note that FDA guidance on off-label marketing would be welcomed, though they also take specific issue with the Obama administration’s concerns over House-passed Cures legislation, which the White House says could “undermine regulatory standards by allowing unproven uses of therapies to be marketed to health care payors [sic].”

The representatives said the Obama stance confirms their “suspicions that HHS has become reflexively opposed to enabling FDA to make even minor policy changes in this space, despite their legal footing continuing to crumble.”

The representatives are also floating a discussion draft of a bill that would create a new type of information companies can provide to doctors as part of what they call a “scientific exchange.”

Under the bill, companies could provide communications on their drugs, biologics or devices that will not be considered “labeling, advertising or evidence of a new intended use,” if those communications include “a conspicuous and prominent statement” that the drug, biologic or device has not been approved for such marketing claims, or that the claims are not included in the FDA-approved label.

Letters to the editor, communications at conferences and dissemination of findings to the “lay media” are included in the list of examples of what would constitute such a “scientific exchange.”

Upton and Pitts Letter to HHS