Will drugmakers get what they're looking for at this week's FDA off-label hearing?



For something to be truthful, should it require well-controlled clinical studies? Who should be the judge of what claims are truthful and not misleading?

Those questions, which get at the core of the issue of off-label pharmaceutical promotion, are part of a debate between drugmakers and the FDA that stretches over two decades. A hearing this week convened by the FDA could set the stage for a regulatory resolution.

See also: Off-label promotion, by the numbers

At issue is whether manufacturers should be able to share information about a therapy beyond the product's FDA-approved label. 

The fact that both pharma and regulators are still battling the matter in court, and that the agency has yet to issue a clear framework, speaks to the complexity involved.

The two-day hearing on November 9 and 10 is the latest episode in the long tug of war between industry and agency, but one in which the parties will have a chance to grapple with some of this complexity, as stakeholders air views on whether truthful and non-misleading information may help, or hinder, healthcare providers and payers in making better decisions.

Physicians can prescribe drugs for any reason if they believe it benefits patients, but drugmakers promoting their products for uses not in the label are considered misbranding under the Food, Drug and Cosmetic Act. Two drugmaker lobbying arms, PhRMA and BIO, released joint principles in July that called for new and clearer regulatory standards to allow drugmakers to communicate with doctors about safe and effective use of their products.

See also: Lobbyists create off-label principles following FDA lawsuits

“I think the pressure has been building for some time,” said Wayne Pines, consultant for APCO worldwide and a former FDA associate commissioner. “These are issues that need to be addressed. We have the beginning of a time table. I would just hope that the agency is not engaged in having this hearing as a delaying tactic to avoid having to make a decision.”

The announcement follows two lawsuits against the FDA that were settled in favor of drugmakers. The cases likely spurred the agency to action even though the issue of off-label marketing policy has been raised frequently over the years.

In 2015 a federal judge in the U.S. District Court for the Southern District of New York ruled in favor of Amarin, which had argued that the First Amendment protects manufacturers from FDA accusations of off-label marketing if the communications are truthful and not misleading. Amarin had been seeking approval to communicate non-approved uses for its fish-oil pill, Vascepa.

Then, in December of last year, the FDA settled a similar case with Pacira Pharmaceuticals. The company had sued the agency after receiving a warning letter for marketing its pain treatment Exparel beyond the two surgeries cited in the company's clinical data. As part of the settlement, the FDA formally withdrew the warning letter and granted the product a new labeling supplement.

Despite the industry push for regulatory changes to off-label policy, the agency has already shared its view on sharing truthful and non-misleading uses of drugs that are off label, in some cases. In 2009 the FDA recognized that the public health may benefit when healthcare professionals receive truthful and non-misleading scientific or medical publications on unapproved new uses in its guidance on good reprint practices, said Kellie Combs, an attorney with Ropes & Gray who represented Pacira in its recent off-label case.

“FDA has acknowledged time and time again that providing access to off-label information is critical to the public health,” Combs said.

Indeed, for companies trying to figure out how the FDA may resolve this issue, it's helpful to look at the agency's previous rulings on communicating these types of information, according to Combs.

“Some of the FDA draft guidance that delinates safe harbors or responses to unsolicited requests — conceptually — all of those docs in some way refer to the idea that if there is contrary evidence you have to share it, and by and large you can't cherry pick information in the public domain,” she said.

Some experts say that the requirement of fair balance, which mandates that drugmakers present information about both the risks and benefits of a therapy, may end up in draft guidance and is consistent with how the FDA wants information disseminated to healthcare providers.

The agency's recent settlements, too, may hint at what may come next from the FDA, which may elect to categorize what kinds of off-label information are required, Combs noted. “With Amarin, there was significant attention [paid by the FDA] to the types of disclosures and disclaimers that may be required to make an off-label statement,” she said.

While drugmakers may view the hearing itself as a victory of sorts, the promotion of off-label uses of FDA-approved drugs remains a contentious issue. The argument against it is two-fold, according to Joanne Hawana, an attorney for Mintz Levin.

“Most doctors say that they don't have time to evaluate all this information and they don't necessarily trust pharma companies to give them unbiased information,” she said. “I think the medical professionals at the executive level of the FDA also have that view.”

Still, the recent lawsuits and settlements in favor of drugmakers may mean that a resolution is the agency's best interest, at least according to industry advocates.

“We hope that the agency would act to address these issues quickly as many of the constitutional issues have been fully fleshed out and developed in case law for some time,” Combs said. “The industry has been looking for clarity for years now and I don't think that this should be further delayed considering how long the FDA has been thinking about these issues.”