Amarin Corp Plc (AMRN)

[HinduKush]

ILT,

I was wondering if you read Bhatt's Epeleuton study? More specifically, the data points that are "relevant" to those studied in Reduce-it to see how they fared head to head? Let's assume Epeleuton showed improved biomarkers over Vascepa. We don't know if any marginal improvement would translate to better CVD RRR? I.E., are there thresholds beyond which cause a diminished benefit, or even further, that could result in harm? Obviously, we're not looking to eliminate biomarkers that our bodies can't do without.

The Epeleuton paper clearly demonstrates albeit in a small population ~30 patients in each arm a dose dependent reduction in liver stifness by Fibroscan (elastography derived liver fibrosis surrogate endpt) accompanied by salutary metabolic and lipid benfits including reductions in facting plasma glucose, TG's VLDL, RLP's, and HbA1C. Interestingly the hs-CRP showed no significant effect but this could be a Type 2 statistical error due to inadequate power to show effect. There were NO safety issues described of clinical significance.
The problem is that while R-IT shows reduction in TG ApoB and hs-CRP none of these things actually correlated with benefit only the serum EPA levels. In other words, we don't know if all the lipid and metabolic effects are epiphenomena (albeit beneficial for CV risk) but may not actually be the mechanism of clinical effect which lies still undiscovered..after all fibrates niacin etc all reduced TG's effectively but languished for clinical benefit, necessitating the R-IT trial to reveal the real actor-EPA itself, pure and importantly unadulterated by DHA .

So while we can show a number of beneficial metabolic parameter changes... nevertheless, without definitive clinical endpoint benefit eg liver fibrosis or enzyme improvement or clear cardiovascular endpoint reduction (would require an R-IT scale trial) none of this adds any commercial advantage to the method of use patents Afimmune (holding comapny) owns today.
Incidentally the structural homology between many putative EPA modified structures touted by different companies (all with ex-Amrn scientific advisors) should not be lost on us. I personally feel all of this relates mechanistically to the structural confirmation and tight retsriction in their physical location within the cell membrane to effect changes in signal transduction and cholesterol domian formation. Here it is summarized:

best HK