Amarin Corp Plc (AMRN)

[north40000]

JL and others: I sent the following via PM to iwfal at dinner time yesterday. He responded with an interesting insight that I did not expect that I will not repeat here.

He can explain later if he wishes.
*****************************************

I sent the following letter to John Thero, CEO of Amarin, in early August 2017. I received no response from anyone at Amarin, nor did I expect one.

The letter contains certain "biomarker" data for me. I thought you might be interested in the "facts" presented in the letter.

"Good morning, John

"My name is [XXXXX]. We own [XXXk] shares of Amarin. I am a Washington, D.C. patent attorney with 25 years experience in patents in Executive and Judicial branches of U.S government(1961-1986), as well as 30 years experience in patent litigation(1986-2016), testifying and consulting as an expert witness in ~ 150 patent infringement suits. I am the Founding Editor of the Federal Circuit Bar Journal. I have degrees in chemical engg from Northwestern University and Princeton University, conferred in 1959 and 1962. I was diagnosed as a Type 1 diabetic in 1957, 60 years ago.

"I now have 4+ years experience with Vascepa that you, Dr. Granowitz, and your patent attorneys may find of interest. Further details are available. I summarize below:

"The EPA/AA ratio is becoming widely recognized as a marker for inflammation in the CV system---my 2016 value of 1.3 is particularly good, probably better than the vast majority of the U.S. population. My 2017 EPA/AA ratio is even better, 1.67. My doctor termed my lipid profile as "excellent," and my cardiovascular risk as "optimally suppressed." Now 80 years old, I have no walking or arthritis difficulties, or other known or common T1 D side effects.

"My DES disappeared within a week of initial Vascepa dosing in April 2013. It remains entirely gone today.

"Below are the 2016 and 2017 lipid panel marker values for me. I have been prescribed 4 capsules/day of Vascepa[an oral capsule containing 96%(1 gram) of an omega-3 fatty acid known as EPA, or icosapent ethyl], Off-label, since 4/1/2013. Family history of CVD and T1 D are in my background. My father died in 1959 from a heart attack at age 51, experiencing his first heart attack 10 years earlier at age 41; his 3 sisters also died from CV events at a young age. I was told that T1 Diabetes is present in relatives in Norway who I never met.

"Medications: Generic Zocor = 40 mg dose > 20 years. T1 diabetic since 1957, 60 years duration. 20 year prescription for 32 units LLY NPH HumulinN U-100 and 7 units of LLY Humalog U-100 with breakfast; 4 units of HumulinN at bedtime.[BP medications and vitamins C, D and E omitted]

"2016 April HbA1c = 6.5; FBG= 111 mg/dL [About the same in April 2017]
2016 Total cholesterol = 144 mg/dL [2017: 125 mg/dL]
2016 LDL-C = 70 mg/dL [2017: 57 mg/dL]
2016 TGCs = 63. " [2017: 60 mg/dL]
2016 HDL = 61. " [about same in 2017]
2016 VLDL = 13. " [about same in 2017]

2016 C-reactive protein = 2.2 mg/dL [2017: 1.4 mg/dL]

2016 APO B = 60 mg/dL; [2017, not measured]
2016 Lp-PLA2 = 216, termed very slightly elevated;[2017, not measured]
2016 EPA/AA Ratio = 1.3; [April 2017 value is 1.67]
2016 Omega-6/Omega-3 ratio = 1.8; [omega-6/omega-3 ratio = 1.6, April 2017]
2016 EPA = 7.0% ; [7.8%, April 2017]
2016 AA = 5.3%; [4.7%, April 2017]
2016 DHA = 2.1%;

2016 Omega-3(EPA + DHA) Index = 9.1%, optimal > 3.2%{April 2017 Index value is 10%] "

***********************************
"Another item that may be of interest, John, in light of my T1 D history. Over the past 2 years, I have slowly reduced the breakfast amount of insulin I had taken daily for many years; now that reduction amounts to ~ 25%[32 U of Humulin N--->24 U; 7 U Humalog--->5 U]. I have done so to avoid the more frequent, serious hypoglycemic episodes I slowly, but surely, had begun to experience. The following excerpt from my April 2017 letter to my PCP, and certain April 2017 articles, may explain why....you may already be aware of the articles:

'You and I have wondered for some time, particularly the past 4 years or so, how my fasting blood sugar levels and HbA1c levels have remained so well maintained.

'The following articles[note the longer one is authored by Chinese researchers] from this past week may present the reason...the 1st link is a summary of the 2nd link:

http://www.medicalnewstoday.com/articles/316756.php

http://www.jci.org/articles/view/87388?key=bbb2df2018c8c18d1e0b

https://www.researchgate.net/profile/Marta_Garcia-Contreras2/publication/305676844_Combination_high-dose_omega-3_fatty_acids_and_high-dose_cholecalciferol_in_new_onset_type_1_diabetes_a_potential_role_in_preservation_of_beta-cell_mass/links/5798cae008aed51475e87894.pdf


'I recall from initial consultations with you, early in my 1st visits as a patient 20 years ago, you thought it was worthwhile to explore whether my pancreatic beta cells, islet cells, were still producing at least some natural insulin. Whatever blood test was performed came back with a totally negative answer to that hypothesis, as I recall.

'I think it is time, in light of the wake-up call provided by the above articles, to again investigate that hypothesis, inasmuch as I have been taking the off-label prescription of 4 capsules/day of Vascepa[each capsule containing 1 gm EPA or icosapent ethyl] for the past 4 years. You will recall we have discussed my serious hypoglycemic episodes occurring over the past year or 2, even with reduced dosages[by 25%] of HumulinN and Humalog that I have been taking vis a vis the prescribed levels of each I had taken for years.

'I would appreciate an opportunity to talk with you re the above, as well as what further investigation is needed now to determine status of islet cells. Do we have frozen blood available/preserved from past visits in the last 4 years to determine progress, if any, with time as the variable, of my islet cells? I am thinking particularly of blood draws in 2013[before any Vascepa to get a baseline] and each subsequent year, especially 2017.[The answer was no]

'I may present a rare case....a "clinical trial" of one T1 Diabetic. Because the Reduce-it Phase 3 clinical trial being conducted by Amarin, the sponsor, remains randomized and double-blinded as to the company, but not the IDMC, we do not know whether T1 Diabetics have been enrolled in that trial. I do not think they are excluded.'

"At this time, John, neither my present PCP, nor a well known, metro-D.C. endocrinologist that I consulted in late May 2017, is willing to express the opinion that Vascepa is the cause of my 25% reduction of daily insulin dose that I have been forced to experience. Both agree there is a correlation. Both are former NIH research physicians. The endo has no T1 Diabetics that also take Vascepa in his extensive clinical practice.

"In light of facts above, you and patent counsel may wish to explore filing a patent application regarding the use of Vascepa in treatment of T1 diabetes, if Amarin has not already done so. I am aware of one published Amarin application relating to diabetes generally. I have data that documents my use of Vascepa[EPA] in Type 1 diabetes prior to the publication date of the above articles.

"My wife and I travel to Europe beginning this coming Monday for vacation---Northern Italy, Switzerland, ultimately Amsterdam, and return to Washington on Saturday, August 19. Should you find it desirable, I am available for consultation with Amarin anytime."

Since that letter to John Thero in August, I have further reduced the amount of Humulin N in the morning from 24 U to 22 U, and Humalog from 5 U to 4 U.
I plan to continue attempts to reduce insulin dose levels in the future---time is the variable, and FBG levels remain in acceptable ranges so far.
I will have further lipid panel values available next week from blood draw on Tuesday this week.