The FDA has settled a landmark case in off-label promotion, giving a company the legal right to promote their drug for unapproved uses, as long as the data “is truthful and non-misleading.” What does this mean for the industry, and what should pharma marketers do?
“You can observe a lot by just watching,” said Yogi Berra. “And when you come to a fork in the road, take it.” For years, we’ve been following legal battles over the right for off-label promotion, and with every win in the courts have wondered what to do next with our messaging and communications. Is each off-label case an isolated instance with unique circumstances, or is the litigation trending in a manner suggestive of a potential paradigm shift in how prescription drugs can and will inevitably be marketed?
Fish Oil & Pain Killers
If this week’s FDA settlement with Amarin Pharmaceuticals is any indication, then the answer is likely the latter. As we’ve covered in a prior blog, their drug VASCEPA (icosapent ethyl) is indicated as an adjunct to diet to lower triglyceride levels in adult patients with severe hypertriglyceridemia; extensive data also demonstrated efficacy for adult patients with “persistently high” levels who were already on statin therapy. As this data was off-label, Amarin requested an expanded indication for that broader patient population.
The FDA denied their request, and Amarin fought back last May, claiming that since the off-label data was shown to be “truthful and non-misleading,” the company had the First Amendment right to communicate data from the studies, including that beyond the drug’s approved indication. By early August, a judge granted Amarin preliminary relief, allowing them to temporarily use the data; and a few days ago the FDA decided not to appeal, enabling the pharmaceutical company to continue promoting VASCEPA off-label.
Although the FDA released a statement that “this settlement is specific to this particular case and situation, and does not signify a position on the First Amendment and commercial speech,” an analogous case with Pacira Pharmaceuticals over their anesthetic EXPAREL (bupivacaine liposome injectable suspension) similarly based on “non-misleading” but off-label data was settled last December, greatly broadening its indication as well. Both brands are now being legally promoted off-label, and the industry is already in off-label conference mode!
Guidance & Websites
The pressure is clearly building: in one corner, the FDA understandably wants to preserve its essential role as the official arbiter of safety and efficacy for prescription drugs; in the other, pharma companies want to share additional clinical data shown to be “truthful and non-misleading” with physicians who ostensibly are already hungry for it. To appease both sides, a comprehensive policy designed to guide industry practices is needed; a third-party review entity has even been suggested, but the onus is clearly on the FDA to make the next move.
Draft guidance on off-label promotion would address these concerns and hopefully provide a viable framework for the industry. The good news is that the Director of the FDA Center for Drug Evaluation and Research (CDER), Janet Woodcock, has said she takes First Amendment rights seriously, and the agency is working on exactly this kind of policy documentation. For now the territory is ambiguous, understandably giving pharma marketers the jitters: What should we do during this intriguing but confusing transition?
A great place to start is by taking a look at how the two brands that have gone through litigation already handle off-label promotion. The VASCEPA website, for example, features the ANCHOR study results for the expanded “persistently high” plus statin patient population with equal prominence as the FDA-approved MARINE study; language that would give experienced pharma marketers pause includes “Data reviewed and confirmed by the FDA—indication not approved by the FDA.” How’s that for a mind-bender?
A telling footnote cites the federal court order allowing the off-label data to be used:
The EXPAREL website is similarly exotic to the eyes of traditional pharma marketers who have learned to live and breathe approved use only, the site devoting an entire page to “important new information” about the drug, including its use “in a variety of surgeries not limited to those studied in its pivotal trials,” along with a message from the company CEO regarding their “successful collaboration with the FDA to resolve this matter” to ultimately provide an “option like EXPAREL to as many patients as appropriate.”
What’s fascinating in both instances is how the off-label promotional content is seamlessly embedded within the conventionally approved content. Standard fair balance in the form of a global ISI containing the approved indication is as you would normally expect, with the off-label data specified as such, yet placed with equal weight and no other overtly distinguishing characteristics. Moving forward, might such lack of differentiation prove problematic, potentially construed as “misleading”? Brave new pharma marketing world indeed!
Inevitability & Surprise
So are these two websites aberrations, or harbingers of a pharma future? Will legacy brands eventually scale to include off-label information the FDA nonetheless deems “truthful and non-misleading,” and in a manner similar to what we’ve seen here? What about other media and modalities, including print and digital journal advertising, display ads, rep-delivered interactive visual aids—and even DTC? To date, the court rulings have only applied to physician messaging—but can consumer messaging be far behind?
Only time (and new FDA draft guidance) will tell. Until then, perhaps even more pressing questions involve the off-label data itself. For both VASCEPA and EXPAREL the FDA was given the opportunity to evaluate if the additional clinical data was “truthful and non-misleading”—but as experts have already observed, those criteria can become far more subjective and intricate as the data becomes increasingly complex. As pharma companies consider the weltering of off-label data available, such criteria will remain top of mind.
“The first step in considering off-label marketing for a pharma brand should involve clearly and precisely identifying the specific claims you want to make, and ensuring they are truthful and non-misleading,” cautions Darshan Kulkarni, Pharm.D, Esq (@FDALawyers). “In light of the recent ‘Yates Memo’ from the Department of Justice that renews focus on corporate wrongdoing, and the aggressive use of the Park Doctrine, it behooves pharma and medical device companies to move carefully through such uncharted waters.”
Along this line, the VASCEPA settlement also includes an optional “preclearance provision” for new off-label claims that Amarin may want to make to physicians, and a dispute resolution procedure—both potentially paving the way for more generalized off-label guidance suitable for the industry. With First Amendment rights at the core, the momentum is already building for a fundamental state-change to how drugs will be marketed, that inevitability likely holding many surprises in how all this will eventually shake out.
Trust & Expertise
Lori Grant, President of Klick Health, recommends a vigilant approach. “All of our goals are aligned; first and foremost we all want to ensure the safety of patients. Along with being truthful and not misleading, it is critical that an abundance of scientific evidence support the safe and effective use of medications. Off-label promotion when done responsibly could bring tremendous value to physicians eager for additional data to help better identify and treat the right patients. But until formal guidance comes from the FDA, we suggest that our clients proactively prepare with partners they trust.”
“You’ve got to be very careful if you don’t know where you are going,” said Yogi Berra, “because you might not get there.” With new FDA guidance issued seemingly every quarter that deeply impacts everything we do, it’s “déjà vu all over again” when it comes to off-label promotion. Do you have a trusted partner to help lead the way? With a fully dedicated on-staff editorial team expertly versed in medical and regulatory affairs, Klick is poised to resolutely and safely help take you there. Contact us to get this vital conversation started!
Special thanks for input from Julie Turnbull, PhD, Lead Medical Editor at Klick Health.