Three months ago, Par Pharmaceutical filed a lawsuit against the FDA contending that its right to convey “truthful” information to physicians is protected by the First Amendment, yet is thwarted by agency regulations governing off-label promotion (here is the lawsuit). At issue, the drugmaker argued, was its ability to talk to doctors who may prescribe one of its drugs for unapproved uses.

In particular, Par was referring to Megace ES, which was approved by the FDA in 2005 to treat anorexia, cachexia or unexplained weight loss in AIDS patients. However, Par did not dispute that some doctors prescribe Megace to treat wasting in other patients, such as the elderly or those with cancer. In fact, the US Attorney in New Jersey is investigating its sales and marketing practices.

The lawsuit was the latest missive by the pharmaceutical industry to attack FDA regulations governing drug promotion - notably, off-label marketing - and claim that such efforts constitute protected speech. Drugmakers are testing this argument the wake of a US Supreme Court ruling last year that struck down a Vermont law about data mining (see here).

Earlier this week, however, the FDA filed a response to the Par lawsuit and excoriates the drugmaker for various positions articulated in its complaint. Specifically, the FDA maintains that Par is incorrect to argue that the agency would seek to press off-label marketing charges that would be based on hypothetical arguments, especially if the drugmaker adheres to the law and refrains from such illegal promotion. Put another way, the FDA maintains the case is not ripe.

“This case is not justiciable because Par does not face a credible threat of prosecution for the future course of conduct alleged in the complaint,” the FDA writes. “Par’s argument rests on a patchwork of false assumptions and misinterpretations of the regulations, and if Par confines itself to the marketing plans and activities specifically alleged in the complaint, it has no reason to fear prosecution on that basis… Par cannot fabricate a justiciable controversy by wrongly anticipating agency action based on a misreading of FDA’s regulations and claiming a need to assuage self-induced
fears.”

Not surprisingly, the FDA also argues that Par is fundamentally wrong to insist its ability to discuss its drugs is crimped - if off-label promotion occurs. “The challenged FDA regulations are fully consistent with the Federal Food, Drug, and Cosmetic Act and the First Amendment, and leave ample room for Par to engage in truthful and non-misleading speech about the approved use of its product,” the FDA continues. “Whatever interests Par may assert are far outweighed by the government’s paramount interests of protecting the public health by ensuring the safety and effectiveness of drugs for their intended uses.” In short, off-label promotion stands as a justifiable reason for prosecution.

But there is more. The FDA then argues that Par brought its lawsuit in a not-so-veiled attempt to derail and undermine the investigation by the US Attorney. As the agency notes, Megace ES has been approved since 2005, but Par never followed-up its own efforts to seek additional indications for the drug, which might have allowed for marketing to cancer or geriatric patients.

To make that point clear, the FDA attached a declaration to its brief from Rachel Sherman, the associate director of medical policy and director of the Office of Medical Policy in the FDA’s Center for Drug Evaluation and Research, along with minutes from various meetings in 2005 between Par and the agency in which suggestions were made for reworking a clinical trial to gain wider approval (here is the FDA brief).

Meanwhile, the FDA also notes in its brief, that Par has admitted to speaking about approved uses to “potentially off-label prescribers” in certain settings, including oncology and long-term care facilities for the elderly. And at the same time, the agency points out that Par maintains that its reps do not speak about approved use to off-label prescribers in settings targeting elderly or cancer patients.

“But there is no principled distinction to be made between these activities in these two settings,” the agency argues. “Whatever Par’s reasons for choosing to promote in one setting but not the other, it was not chilled by a fear of prosecution, and Par’s alleged harm is self-inflicted and unnecessary. Nor has Par explained why, if its fear is real and its motivation is to clarify its First Amendment rights, it waited until this late hour to file suit - after marketing Megace ES for six years, and without any intervening change in the governing regulations or FDA’s statements about how it interprets them.”

In short, the FDA is arguing that Par acted prematurely and is using the newly emerged debate over off-label promotion and protected free speech to avoid the threat of criminal prosecution. “If and when that investigation leads to any enforcement action against Par, the government’s case will rest on the full range of evidence regarding Par’s past conduct that has been developed in that investigation. Par will be free to assert any constitutional defenses to such an enforcement action in the course of that proceeding.”

One regulatory expert says the scenario is reminiscent of a case involving Allergan, which paid $375 million and pleaded guilty to one misdemeanor count of misbranding in connection with off-label marketing of its Botox med for various unapproved uses. The drugmaker also paid $225 million in fines to cover civil claims asserted by the DOJ under the False Claims Act (back story).

As part of the deal, however, Allergan was required to dismiss its First Amendment lawsuit (here it is) in which the drugmaker sought to win the right to distribute information about unapproved uses for Botox in the context of providing scientific and medical info to doctors. Allergan claimed an FDA ban on off-label marketing violated its First Amendment rights to free speech.

“I see this in much the same way as the Allergen lawsuit,” says Arnie Friede, a former FDA associate chief counsel and a former senior corporate counsel at Pfizer. “I always thought that case was an effort to gain leverage in the negotiations. Allergan paid $600 million, but it’s hard to know if the lawsuit actually made a difference.

“In any event, I think the government has done a very effective job (in the Par brief) of saying ‘Look, whatever is going on in that investigation is all well and good, but that’s not what this case is about.’ And, according to FDA, it’s not a ‘case or controversy’, in any event, because what Par is saying it wants to do is not a violation of law. According to FDA, if all that the company wants do is what it lays out in its complaint, then that’s not a problem by itself. But if there’s some other scheme we don’t know about, then FDA, according to the brief, reserves the right to examine that separately. But based on what’s in the Par Complaint, FDA says it won’t prosecute. So what’s the big deal?”

“I think government is right on this point. I think this is an effort by Par to gain leverage in the DOJ investigation. On the other hand, I think the government makes a very strong case that there’s no controversy here… As FDA notes, if Par is shivering because it perceives a ‘chill’ in its First Amendment rights, that shivering is for its own reason, but not because Par risks any appreciable danger of prosecution for the limited activities in lays out in its complaint.”

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