In August 2015, the Food and Drug Administration (FDA) reached a unique settlement permitting Amarin to promote its prescription fish oil pill for off-label uses. Only a few years ago, Big Pharma giant Johnson & Johnson agreed to pay $2.2 billion to settle charges of false marketing practices. Due to a slew of recent hefty penalties ranging millions to billions of dollars, most pharmaceutical companies have recognized they are subject to elevated legal, regulatory, and public scrutiny. The community’s eyes are cast upon tiny Amarin to see whether it can turn Pharma’s nefarious reputation around by displaying squeaky-clean ethics and scientific rigor in light of the nebulous marketing leeway established from the ruling.
Fish oil 101
Michael Pollan’s seminal 2006 book, The Omnivore’s Dilemma and Robert Kenner’s documentary Food Inc (2008) have brought food technology and the agribusiness to forefront of popular culture. The food revolution is underpinned by the fact that our diet has drastically changed over the past 10,000 years, yet our genes have changed very little. The spontaneous mutation rate for nuclear DNA is estimated at 0.5% per million years. Thus, over the past 10,000 years, our genes have only changed at a rate of 0.005%. In particular, the ratio of our consumed omega-6 to omega-3 fatty acids radically changed over time. This ratio during the Hunter Gatherer and Agriculture phase of our diet was approximately 1:1. However, recently this ratio in Western culture has ballooned to 10/1-25/1, indicating we are significantly deficient in omega-3 compared to our ancestors. The dearth of omega-3’s in our diet has generated substantial awareness, which has lead to prevalent commercially available products like fish oil.
Vascepa (Amarin) vs. Lovaza (GSK) vs. Generic
There are 3 types of omega-3s: EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and ALA (alpha-linolenic acid). EPA and DHA are derived from fish traditionally, whereas ALA comes from walnuts, chia seeds, soybean oil, and flax. The type of omega-3 is notable because the ratios of omega-3’s are what differentiates the various commercially available products: Amarin’s Vascepa, GlaxoSmithKline’s blockbuster drug Lovaza, and the generic over the counter fish oil. To note, Vascepa has the highest relative EPA, Lovaza has the highest relative DHA, and Dr. Tobias (highly ranked generic on Amazon) has the highest relative excipient/filler.
Timeline of significant events
In 2004, the FDA approved Lovaza (developed by Reliant) to reduce triglyceride levels in adult patient with severe (≥ 500 mg/dL) hypertriglyceridemia. In 2007, GSK acquired Reliant and with GSK’s powerful marketing machinery behind Lovaza, it became a blockbuster prescription.
In 2012, a competitor arrived on the scene concomitant with the FDA’s approval of Vascepa (Amarin) for the same indication of reducing triglycerides in adult patient with severe (≥ 500 mg/dL) hypertriglyceridemia as per findings from the MARINE clinical trial. Amarin conducted a second clinical trial called ANCHOR, which was designed to treat patients with high, but not severe, triglycerides (200 mg/dL to less than 500 mg/dL). It is not a coincidence that the ANCHOR study enlisted a patient population for which Lovaza did not and still does not have an indication as doctors sometime engage in writing off-label prescriptions. If Amarin could expand the Vascepa label to contain a population for which doctors were already writing off-label prescriptions, Amarin could effectively commandeer that market by providing those hedging doctors with a less risky alternative in our highly litigious country.
In 2013, an FDA panel voted against recommending such an expanded drug label for Vascepa. Not surprisingly, Amarin shares aptly plummeted and have yet to recover. In spring of 2016, the FDA agreed not to appeal a court ruling that said Amarin had a free speech right to tell doctors about studies supporting the use of Vascepa for indications not approved by the FDA as long as they are truthful. This agreement set up an optional protocol for Amarin to submit marketing materials to the FDA for approval twice a year if it seeks to obtain preclearance of marketing material. “With more truthful and nonmisleading information readily available to healthcare professionals about the potential of Vascepa to improve cardiovascular health, this settlement serves the public interest by supporting informed medical decisions for tens of millions of patients with persistent high triglycerides,” said John Thero, Amarin’s chief executive in a statement .
The FDA and cardiovascular community is waiting with baited breath as Amarin is slated to publish in 2018 their 8,000-patient study, REDUCE-IT, to assess whether Vascepa prevents heart attacks, strokes, and certain heart procedures in people with high triglycerides.
Future of Pharma marketing
“This is an interesting development, but I don’t think it changes how companies can market their drugs,” said Patti Zettler, a former FDA associate chief counsel who is now a Georgia State University College of Law professor.
The truth of the matter is there will be no head-to-head trials–for fish oil or any other pharmaceutical drug. Clinical trials cost millions, capital of which only Big Pharma can front, and no one wants to conclusive evidence their product is inferior to a competitor. The litany of research conducted and opinions proffered does not provide a consensus for whether or not fish oil (Vascepa, Lovaza, or generics) is the panacea to heart disease, which is the leading cause of death for both men and women in America. But fish oil also hasn’t really definitively killed anyone either? Perhaps certain combinations of omega-3s work best for specific patient populations, but those indications have never been teased out and are extremely difficult to tease out in onerous clinical trials.
Whether Amarin can navigate these uncharted off-label marketing waters will determine the trajectory not only of this tiny one-trick-pony Pharma company, but also determine partially the fate of Pharma’s declining reputation and future marketing tactics.
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