Amarin Corp Plc (AMRN)

[HDGabor]

I try to summarize the key point regarding the mineral oil.

Let’s start with the final sentence of FDA: “These results suggest the changes in ANCHOR are atypical, but the etiology of this remains unclear”

Choice of Placebo - Corn oil, which had been used as a placebo in other trials of omega 3 polyunsaturated fatty acids, contains triglycerides and has a distinctive yellow color different from icosapent ethyl (colorless). Therefore, Amarin proposed to use light mineral oil, NF, in the placebo capsules for the pivotal studies. The FDA agreed that light mineral oil was acceptable as a placebo as long as the amount per capsule did not exceed the amounts in FDA-approved products given by the same route of administration.

FDA already noticed during the review of the MARINE data, that several lipid parameters increased from baseline to week 12 in the placebo group, treated with mineral oil (and earlier in case of Lovaza trials also, and these trials did not use a mineral oil placebo), however no strong evidence for biological activity of mineral oil was identified. (Note: The LDL-C change in the placebo arm was -3,0, -8,0% w statin, 0% w/o statin).

FDA analyzed the placebo group in their BD (PDF page 57-59 / Page 53-55 of 94, 5.5 Placebo Group Effects) and Amarin presented mineral oil related slides Amarin Presentations ((PDF page 99-103 / CM14-19)


All AdCom Materials (scroll down the page to find as October 16, 2013 Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee)

My view: Since the result was atypical it’s normal that the FDA raise this "issue". However, meanwhile the FDA definitely screwed AMRN, they did / could not come to the conclusion that the mineral oil is not inert. The strongest that they could say was: “These results suggest the changes in ANCHOR are atypical, but the etiology of this remains unclear”

The issue already discussed with sponsor, relayed concern to DMC of R-IT. I think it will be analyzed again for R-IT, however they will not have any evidence about “not inert” and if – as expected – eff.% will be greater than 20-25% it will not affect the approval.