Amarin Struggles Show Why Choice of The Right Placebo is Critical  
​[Thursday, November 15, 2018]

Last week Amarin announced the results of its large Phase 3 with the fish oil product, Vascepa. The trial showed remarkable improvement in cardiovascular events compared to placebo, however, patients on placebo showed higher than normal incidence rate for the same events that Vascepa is supposed to improve raising questions if the placebo over-inflated the response to the drug. The placebo in question was mineral oil chosen because it looks and feels the same as the active drug, making it possible to blind the study. However, it is hard to predict the effect of the placebo so well-known as mineral oil. Mineral oil is a GRAS (Generally Recognized As Safe) ingredient and a common ingredient used for placebo. Before this study, mineral oil was not suspected to be associated with increased cardiovascular events. Numerous times placebo has been suspected to add to the positive effect thereby dulling the overall effect of the active but this selection of a placebo that makes the drug look better than it potentially is could either be a stroke of good luck or push Amarin down a long, drawn process to show that its drug actually works as well as claimed. The results of the trial have been poisoned by doubt. It is hard to blame Amarin for the choice of the placebo but no matter what the company will end up paying the price for the unexpected results; if approved, the claims will be tainted by the negative publicity, and if not approved, it would be waste of years of efforts on a very expensive Phase 3 study. This should be lesson to all sponsors that selection of the placebo is a critical decision that should be vetted as vigorously as any other decisions regarding a given trial.