Omega-3 fatty acids are a curious medicinal beast – more than just nutritional supplements, but not fully accepted as a pharmaceutical therapy for dyslipidemia. Research in the Seventies first highlighted that diets rich in seafood were associated with lower rates of cardiovascular (CV) disease, and since then substantial amounts of epidemiological evidence has supported this position. Further studies have shown that omega-3 fatty acid compounds can reduce triglyceride levels and improve other CV biomarkers, but the mechanisms for doing so remain unclear. However, as in the case of many investigations of essential nutrients, studies where omega-3 is added in the form of supplements or medicines have not been as positive in terms of hard outcomes as those based on diet. And to reinforce this, the latest edition of the Agency for Healthcare Research and Quality (AHRQ)’s Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review, released on October 4, 2016, has once again evaluated the evidence for omega-3 fatty acids and cardiovascular outcomes and once again found them wanting.
Despite the lack of conclusive benefit, there are a number of relatively widely used branded and generic prescription omega-3 fatty acid products available, including Abbott/GSK’s Lovaza/Omacor. Indeed, in Europe these drugs are indicated in patients who have had a myocardial infarction as well as in those with high triglyceride levels. So, why has proving conclusively that prescription omega-3 fatty acid compounds provide CV benefits been such a struggle? In most cases, I would suggest that the effects of these drugs just aren’t in the same league as the statins, with respect to reducing CV risk, but it has also been because low doses of the omega-3 fatty acid compounds have been tested. Whether this was due to financial reasons, false belief in the strength of the drug candidates, or attempts to optimize compliance is not clear.
Three new CV outcomes trials are ongoing, but are these trials going to provide any more clarity than those already conducted? Well, yes. And no. AstraZeneca’s STRENGTH and Amarin Corporations’ REDUCE-IT outcomes trials are evaluating Epanova and Vascepa, respectively. Both trials are using prescription doses of each drug in large numbers of statin-treated patients. However, the independent ASCEND outcomes trial is evaluating only 1g of omega-3 fatty acid compounds (with or without aspirin) in diabetics.
As many physicians consider the omega-3 products to be broadly similar, regardless of component acids, and confidence in their benefit is mixed, will the results for REDUCE-IT, STRENGTH, and ASCEND reel in new payers and net additional prescribers? Or will the class fail to land new physicians and let payers off the hook? We believe that modest to moderate improvements in CV morbidity will be netted for Vascepa and Epanova, but a reduction in all-cause mortality might be the one that got away. The ASCEND result will likely muddy the waters and keep scientists fishing. As a consequence, there will be gains in market share for both Vascepa and Epanova, but these will be limited as there are plenty of generic omega-3s in the sea.