A recent American circuit court ruling has legalized, within its jurisdiction, the off-label promotion of prescription drugs if the off-label clinical data is deemed “truthful and non-misleading.” How did this happen, what does it mean for the industry, and what should you do now?
The first and most fundamental rule we learn as pharma marketers is to never promote any prescription drug or device “off-label.” That means every claim ever made for marketing purposes must be vetted and approved by medical, regulatory, and legal experts who ensure it falls squarely within the FDA-mandated indication that specifies exactly what the drug is approved to treat, and for whom.
These claims must automatically be accompanied by fair balance, disclosing in detail the drug’s safety and risk profile. The totality of that data is derived from FDA-scrutinized clinical trials, a prerequisite for any drug being approved within the United States. The entire system is in place to help ensure the FDA mission “for protecting the public health by assuring the safety, efficacy, and security” of drugs and restricted medical devices.
Since the indication of a drug is limited to the particular patient population and particular disease state evaluated by the FDA-assessed clinical trials, healthcare professionals can be assured that the efficacy and safety of that drug has been tested, and the clinical data deemed truthful and non-misleading. But is that all the “truthful and non-misleading” clinical data that’s available for a drug?
Typically not: Prescription drugs and their interactions with the human body are incredibly complicated, and hardly limited to the highly restrictive data sets and end points provided by these clinical trials. Researchers are constantly conducting their own clinical trials of these same drugs, evaluating them for varying dosing levels, diverse patient populations, and even different real and surrogate end points.
Clearly this additional data is valuable to the medical community, even if off-limits for promotion due to off-label concerns. On their own, however, many of these studies may not meet the “truthful and non-misleading” standard, but some will—such as the tantalizing and potentially game-changing scenario we’ll discuss in a second.
Because of this rigid distinction between on- and off-label data, pharma companies have created a “church/state” separation between marketing and communications by the medical affairs department: The former handles promotion and is therefore limited to the use of FDA-approved data and messaging only; the latter provides an objective and comprehensive educational resource for medical professionals, devoid of any promotional intent, and only when specifically requested by a healthcare professional.
And there’s the pharma rub: Although mountains of truthful and non-misleading additional clinical data are typically available for most drugs, the company can use none of it for promoting the product. Even if the additional data demonstrates efficacy for an expanded patient population, or administration at a different dose, or a novel combination treatment, the drug can never be promoted to that broader target population or for that different dose or treatment.
Fearing an FDA Warning Letter, pharma marketers have without question accepted and followed these rules to the letter. An essential part of doing business in a highly regulated environment, avoiding off-label promotion for us comes as naturally as the use of linear algebra for a mechanical engineer, or differential equations for a rocket scientist. Without them our buildings fall, our launches fail—until now.
The Amarin Case: A Seismic Disruption in Pharma Marketing
VASCEPA (icosapent ethyl) from Amarin Pharma Inc., is the first FDA-approved EPA-only Omega-3 fatty acid prescription product, indicated as an adjunct to diet to lower triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.
But extensive off-label data from the ANCHOR study published in The American Journal of Cardiology demonstrated that VASCEPA is also efficacious for adult patients with “persistently high” (≥200 – 499 mg/dL) TG levels who were already on statin therapy. Since this additional clinical data was shown to be “truthful and non-misleading,” Amarin asked the FDA for an expanded indication to accommodate this broader patient population—but was denied.
In May, Amarin fought back in court, claiming the FDA violated the company’s First Amendment rights by restricting its ability to legally communicate truthful and non-misleading drug benefits, including those formally outside the drug’s indication. Their defense echoed the Caronia case of a few years ago, where a sales rep was found not guilty of off-label promotion based on a freedom of speech argument.
The result: in early August, United States District Judge Paul Engelmayer granted preliminary relief to Amarin on two points: 1) the company can engage in truthful and non-misleading speech promoting the off-label use of VASCEPA, and that this speech will not form the basis for prosecution as misbranding, and 2) the statements and disclosures provided to the court were truthful and non-misleading, and thus could be used.
Really? Really really. Although the government can still appeal this decision, the outcome nonetheless heralds a brave new world where the use of truthful and non-misleading off-label speech for pharma promotion to healthcare professionals is permitted. Think about that: The fundamental axiom of pharma marketing has seemingly crumbled, a drug company now allowed to promote their prescription drug off-label (given these special terms and conditions).
What now? Since the Caronia case, the pharmaceutical industry has been slow to react in any substantive way because the FDA has asserted that the court made a very specific ruling that was not applicable outside a very limited and specific set of facts. The Amarin court transcended this reading of Caronia, however, and has now bumped the stakes up a few notches.
For a peek at what’s likely to come, go no further than the VASCEPA HCP website itself, where a bold interstitial seems as beckoning as it remains bizarre to the pharma marketing eye, pushing the envelope with “Additional Data” that links directly to a downloadable multipage PDF of the off-label ANCHOR clinical trial:
“Amarin may now disclose additional truthful, non-misleading information not included in the VASCEPA (icosapent ethyl) Prescribing Information to healthcare professionals.” Amazing! Like conducting a physics experiment where an object is measured to exceed the speed of light in a vacuum, these words and what they imply seem impossible, screamingly violative, and almost surreal—or a demonstration in how to inappropriately market a prescription drug.
But real it is, with the additional off-label clinical information not only available through the interstitial, but built right into the HCP website itself across a header banner located above the main navigation:
Agency Backlash and New Guidance
Now that the industry has reacted, how will the FDA? Without evidence of fraud or deception, the Second Circuit’s District Court’s decision will be difficult for the FDA to fight—but the government has a number of options, each of which are potentially significant for the ruling: appeal, settle, or continue its defense in the proceeding litigation.
Meanwhile, Darshan Kulkarni, Pharm.D, Esq. of the Kulkarni Law Firm (@FDALawyers) recommends that his clients consider and plan for the future, but for now wait until the FDA explains their interpretation of “truthful and non-misleading” data. He also points out that the FDA has revealed that new guidance is coming, hopefully providing sufficient clarification and guardrails.
Accordingly, the precedent set by freedom of speech cases, as well as the updated language in the 21st Century Cures Act regarding the sharing of off-label economic data with payers, reinforce the reality that the pharma marketing landscape will evolve and expand to one where more and more drugs will be actively promoted off-label using truthful and non-misleading data.
Facing these sweeping changes, what should you and your brand do?
Implications and Recommendations
In many ways the VASCEPA case was unusual, considering that similar products are essentially dietary supplements and not, for example, a complex oncology drug. The court ruling made specific note of this, stating “there is no basis to fear that promoting VASCEPA for this off-label purpose would endanger the public health,” while acknowledging they would not object to the marketing of VASCEPA as a dietary supplement.
Nonetheless, this case is relevant to all prescription products, leading the way for sweeping changes welcomed for treatments that have demonstrated broader effectiveness outside their indication boundaries. But as my mom used to say, “Just because you can do something, doesn’t mean you should”—sound advice, also shared by the court:
…there is practical wisdom to much of the FDA’s guidance, including that a manufacturer vet and script in advance its statements about a drug’s off-label use. A manufacturer that leaves its sales force at liberty to converse unscripted with doctors about off-label use of an approved drug invites a misbranding action if false or misleading (e.g., one-sided or incomplete) representations result.
In other words, the license to promote off-label to healthcare professionals is predicated by ensuring that all communication remains truthful and non-misleading, demanding as much if not more care and scrutiny. Central to this is definitively substantiating that the data satisfies these criteria, in lieu of an official approval process and guidance from the FDA. Equally important is ensuring that all marketing channels control how that off-label information is shared, and with whom.
Throughout this process, brands and their marketers must remain focused on providing increased insights and value to patients and healthcare professionals. End of the day, the FDA mission to protect the public health must be maintained, on- or off-label.
Summary and Key Takeaways
- Off-label promotion is now actually permitted, within certain jurisdictions, if the data is shown to be truthful and non-misleading
- The court decision is still subject to appeal but solidifies an already powerful freedom of speech precedent
- Amarin has already demonstrated how off-label information may be embedded within a public domain website (though the jury is still out on how the FDA will react)
- The bottom line is that all data and messaging should be truthful and non-misleading, and ultimately beneficial to healthcare professionals and the patients they serve
- That means the ruling is not a license for a free-for-all of off-label promotion by the sales force and/or marketers, and language should be scripted and vetted before being used
- The best advice to brand teams is to wait and see for now, while considering truthful and non-misleading off-label data for the potential usage in promotional speech and content
- Questions? Consult with medical, regulatory, and legal experts every step of the way, and engage pharma marketing partners and thought leaders you can trust
Special thanks for input from Julie Turnbull, PhD, Lead Medical Editor at Klick Health.