Amarin Corp Plc (AMRN)

[Thonn]

Question: How to explain the positivity of the REDUCE-IT trial, when all the other primary or primo-secondary cardiovascular prevention trials that were carried out with omega-3s in the same period failed? I put aside in this question the JELIS study since it is a Japanese study with all the particularities of Japan, and the results are difficult to transpose to a European population.

Answer: On the discrepancy between the other trials with omega-3s and the REDUCE-IT trial and the JELIS study, it seems to me that the first explanation is the dose. That is, only three trials tested high doses of omega-3s, namely STRENGHT, JELIS, and REDUCE-IT. All of the other trials, including VITAL, ASCEND and all of the previous trials, tested doses that were less than 1 gram per litre, sometimes using commercial omega-3 supplements as well. However, we know that commercial omega-3 supplements have a content that is in fact often lower than that advertised, that they often contain oxidized liquids, and that their pharmaceutical quality is not absolutely ideal. It is known that oxidized lipids, in particular, are probably deleterious. Too low doses, with unreliable omega-3s, explain in my opinion the lack of effect of the other trials. For me, the real discrepancy is between STRENGHT on one side and JELIS and REDUCE-IT on the other, since these are the three trials that used high doses. Here, we are forced to note that STRENGT uses EPA and DHA, which have biological effects that are still notoriously quite distinct, and that the two positive tests use pure EPA. The two high-dose pure EPA tests are positive. All EPA/DHA tests are negative, and all low dose tests are negative. I think it is therefore the fact of using EPA in high doses that explains the discrepancy.

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