Why the Amarin Settlement will have Little Impact on Pharma Marketing in the U.S.

“The reports of my death have been greatly exaggerated.” – Mark Twain

Following the results of the Amarin legal judgment, there has been speculation that the ability to promote unapproved, “off-label” claims for prescription drugs will dramatically change. Yet, there are specific reasons why the Amarin First Amendment legal case succeeded and hundreds, if not thousands, of other cases have failed. While the Amarin judgment has set a precedent, it should not have a dramatic change on promotional claim requirements in pharma marketing – meaning that companies do not have First Amendment protection for statements that are untruthful and misleading. It’s not expected that the FDA will diminish the criteria needed to support substantial evidence of efficacy. Instead they will continue to vigorously protect public health and the communication of accurate, science-based information.

Why is the Amarin case a unique situation? The product, Vascepa (icosapent ethyl), was already approved for severe hypertriglyceridemia. Their ANCHOR randomized, controlled clinical trial (RCT) for patients with mixed dyslipidemia on statin therapy was conducted under a Special Protocol Assessment or SPA agreement, using a clinical protocol and endpoints agreed upon with the FDA. Vascepa met all pre-specified ANCHOR endpoints. Amarin had also initiated a longer-term RCT, REDUCE-IT, which was also conducted under SPA agreement to confirm the cardiovascular benefit.

The product was reviewed by an Advisory Committee on October 16, 2013, where the majority of the committee (9 of 11) voted against approval for an expanded indication. The committee cited that “…the results of ANCHOR were promising, but FDA should wait on the final results of the CV outcome trial, REDUCE-IT, before approval” due to the uncertain clinical benefit.

While the Amarin case does provide precedent for “off-label” pharma marketing, those companies that successfully litigate in the future will likely face increased liability risk, since they will be held accountable for truthful and non-misleading communications, and will need to justify the lack of FDA approval for the “off-label” should personal injury occur.

RCTs will still be the accepted method to most accurately collect the clinical data needed to demonstrate benefit-risk. Conversely, non-RCTs like uncontrolled studies, open-label studies, real world experience, and observational studies lack statistical and scientific rigor. Thus, companies pursuing First Amendment litigation will likely need an RCT to both demonstrate truthful and non-misleading communications and FDA agreement for off-label promotion.

Companies will still need to submit an application for approval containing substantial evidence of efficacy and support for acceptable benefit-risk in order to gain approval. That approval is the accepted benchmark for demonstration of acceptable benefit-risk and is often referenced during legal liability cases. Therefore, it is likely that the company will need to demonstrate a commitment towards gaining the eventual indication in order to successfully promote “off-label” claims.

The Amarin results may create false hope for many, likely increasing the number of First Amendment legal cases against the FDA as companies seek to promote “off-label.” Should this occur, it will place dramatically increased resource and financial burdens on an already under-budgeted federal agency. The knock-on effect from the increased legal battles could be delays in drug, biologic, and device approvals and increased user fees.

In the short term, companies may believe that incurring the cost of litigation is the way to proceed. But the long-term ramifications for “off-label” liability exposure and the ability of the FDA to meet Prescription Drug User Fee Act (PDUFA) targets are troubling.

 

ABOUT THE AUTHOR

Kell Cannon brings more than 20 years of U.S. and global lifecycle and pharmaceutical marketing expertise to 3D’s clients. Kell has developed rigorous processes to help clients analyze and prepare their regulatory submissions and FDA Advisory Committee presentations. This assistance enables companies to win approval, expedite product access, and achieve competitive reimbursement. Connect with Kell on LinkedIn.