DB..
I have been checked out on Linkedin by FDA attorney Michael Varrone . Not as JL, but as my real name..It may have had to do with this letter I sent to FDA head Margaret Hamburg. I am not aware of anyone else being "checked out"
My name is (Name omitted) and I am a fellow HMS graduate. I have a strong family history of Type2 DM. My specialty is plastic surgery, but I was a combat surgeon in Viet Nam in 1972-1973. I have run a burn unit in the past and in the course have studied and learned much about wound healing and inflammation. I have served as an adviser to the group at HMS which includes Tracy Keller and Malcolm Whitman who are studying novel methods of controlling inflammation.
I would ask you to consider the possibility that chronic inflammation is the most important disease process in the USA today. T2DM, atherosclerosis, most other degenerative diseases, those "age related" simply represent the outward manifestations, the symptoms of a common pathophysiological process which involves hyperactivity of the inflammatory-immune axis. In one sense these are no more separate diseases than the cough, sore throat, headache, and malaise seen in a URI.
There is strong scientific evidence that the rise in these diseases can be traced back to the 1940s. At that time technology perfected seed oil extraction, which allowed processed food manufactures to add n-6 rich seed oil highly resistant to oxidation to their products. Thereby increasing shelf life and making supermarkets practical. This lead to great increases in dietary
N-6, which is a substrate for Arachidonic Acid and acts in the eicosanoid system to increase resting inflammatory levels. The American diet is also high in glycemic index carbohydrates which also promote inflammation.
On Oct 16th 2013, the M&E division conducted an Adcomm on Vascepa. Vascepa is pure EPA, a component of fish oil. The Adcomm was convened as an eleventh hour meeting to discuss two issues. The first was to discuss an upcoming sNDA decision, to be announced on Dec 20th 2013 regarding a label change which would allow Vascepa to treat the much larger mixed dyslipidemia population. The second issue was the FDA conditions attached to the SNDA. The most important condition was an SPA agreement which in essence said the FDA would allow the label expansion if Amarin (the sponsor) would complete a 12 week blinded study involving patients all taking adequate doses of statins. The study being clinical and lab one group taking Vascepa the other placebo. Vascepa surpassed all FDA endpoints, and there were no significant safety issues. The second requirement was for Amarin to plan and have a large FDA approved clinical outcomes trial (REDUCE-IT) substantially underway. Early in 2013 the FDA notified the company it had met these conditions. In fact the FDA allowed an amendment to the SPA in May 3013.
There was the usual proviso that the SPA could be rescinded if the director of the FDA division discovered important scientific issues, pertaining to safety or efficacy. The FDA proceeding into the Oct 16th had made no mention of any concerns to the company up until this juncture.
The Adcomm was deeply disturbing on several levels. The first is that there was no discussion or even any mention of how Vascepa's API worked or what exactly it was. I'm sure Dr. Hamburg you have heard about how the FDA was extrapolating from clinical trials involving drugs not vaguely related to EPA to predict the results of the Vascepa and using this as one basis for rescinding the SPA. This after Amarin had been fooled into spending millions of dollars based on the premise the FDA could be trusted...
But this was not even the worst thing about this "trial”. It was clear from the proceedings that neither the FDA, nor its expert panel knew anything at all about n-3s, other than they are found in fish oil. There is a telling point when all of these panelists gave the reasons they voted to deny the label application. Virtually none of these responses contained a lick of science. Half the panel was lay people and should have been disqualified. The clinicians all considered Vascepa an exotic form of statin that lowered trigs. So the argument got down to whether lowering trigs will lower CVD risk in patients taking statins....This is the wrong question. The question should be does EPA lower CVD risk in patients on statins. To answer that question you need people who know something about EPA. Not the case here.
So what information supports EPA…? There is a ton of it, but let me give you a couple of examples… The first is a population study comparing Japan and the USA. In a population adjusted for age and sex the Japanese and Americans had an average LDL-C which was essentially the same, the CDV event risk was 71% higher in Americans even though the LDL-C was the same. What was different was the EPA/AA ratio was 70% higher in Japanese…Think about that…
The second example is T2DM. The risk of CVD events in diabetics is much higher than non-diabetics for the same lipid parameters. What is known is insulin resistance is the root cause of T2DM and insulin resistance is caused by systemic inflammation.
name omitted ":>) JL
AI
