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ex, a bird (NCE) in the hand is worth two (patents) in the bush.
Patients who underwent angioplasty with stent and then treated with statins has annual MACE event rate of 12.6%.
"Patients with MACE showed significantly higher TG level at 4 weeks (149.6±81.4 vs. 119.3±58.9 mg/dL, p=0.026) than those without. High on-treatment TG level (≥150 mg/dL) were associated with increased adverse events compared to lower TG level in a univariate analysis (hazard ratio [HR], 3.3; p<0.001). In a multivariate analysis, high 4-week TG level after statin treatment was an independent predictor for MACE (HR, 4.01; 95% confidence interval, 1.85 to 9.06; p=0.001),"
"At 4 weeks, the mean LDL-C level was 72.5±23.8 mg/dL and the mean TG was 123.2±62.8 mg/dL. Of the patients, 49.8% had LDL-C ≥70 mg/dL, and 24.3% had TG ≥150 mg/dL. The patients with MACE had significantly higher on-treatment TG level than did those without (149.6±81.4 vs. 119.3±58.9 mg/dL, p=0.026, Table 2). Low on-treatment LDL-C (<70 mg/dL) was not associated with MACE compared to higher LDLC in a univariate analysis."
See Table 2 of the following link,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784976/
So seems like 5.2-5.9% R-IT placebo group event rate is very achievable as I believe Kiwi had mentioned R-IT strives to recruit patients with prior CVD and stent procedures done. Moreover, Amarin seems to pick the right TG threshold of >150 with mean and median exceeding 200 for R-IT patients. I am shocked that no US/EU BP has ever conducted a high trig. CVOT utill R-IT. Aren't scientists and healthcare professionals curious at all? I don't care what's AMRN stock price now. I just glad I am a shareholder.
Generic companies such as Watson would sue FDA immediately for such exceptional ruling and win.
I promised you no more comment from me on this topic. Rumor works sometimes. Case in point,
Intel's Rumored Acquisition Of Altera Could Protect Its Massive Monopoly In Servers,
http://www.forbes.com/sites/aarontilley/2015/03/28/intel-altera-acquisition-rumor/
Couple months later,
Intel Ends The Rumor Mill, Plans To Acquire Altera To Spur Internet of Things Business
http://www.crn.com/news/components-peripherals/300076983/intel-ends-the-rumor-mill-plans-to-acquire-altera-to-spur-internet-of-things-business.htm
I did mention about the Altera rumor in this board on 5/6/15, see post# 48864
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=113420903
Clinical Significance of On-Treatment Triglyceride Level in Patients Treated by Percutaneous Coronary Intervention for Non-ST-Segment Elevation Acute Coronary Syndrome,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784976/
"High on-treatment TG level (≥150 mg/dL) were associated with increased adverse events compared to lower TG level in a univariate analysis (hazard ratio [HR], 3.3; p<0.001). In a multivariate analysis, high 4-week TG level after statin treatment was an independent predictor for MACE (HR, 4.01; 95% confidence interval, 1.85 to 9.06; p=0.001)"
I would like to say that Geoff Foster has a good track record of biotech reporting,
He speculated GSK for HGSI in Oct 2011,
http://www.thisismoney.co.uk/money/markets/article-2050257/MARKET-REPORT-GlaxoSmithKline-just-tonic.html
The deal was subsequently announced in July 2012,
http://dealbook.nytimes.com/2012/07/15/glaxosmithkline-in-talks-to-buy-human-genome/?_r=0
Geoff Foster speculated on AZN for Amarin in Oct 2012
http://www.thisismoney.co.uk/money/markets/article-2221989/New-AstraZeneca-boss-planning-launch-cash-bid-US-biopharmaceutical-group-Amarin.html
AZN acquired Omthera in May of 2013,
http://www.astrazeneca.com/Media/Press-releases/Article/20130528-omthera
There might not be an actual price offer for Amarin because the buyer and seller couldn't agree on a price due to NCE uncertainty, IMO.
How can FDA rules no NCE? The 60-day appeal period has long expired.
I welcome "con" along the lines of R-IT should fail because
1) R-IT trial design is flawed
2) scientific paper proving lowering trig. doesn't lower CVD
3) supporting info. showing 5.2% event rate might be too optimistic, etc.
Not endless rant about the stock price.
Mo, have you considered the fact that the stock market is not always perfectly efficient. Rather than complaining about the stock price, why don't you take advantage of the situation?
You come here to bitch, rant and trash without bringing anything concrete to support your opinion. You are not the only one that has a high cost basis for the stock. I highly suggest you to channel your frustration to more productive matters such as investigate the strength of Amarin's patents, why R-IT should fail/succeed, etc.
2024, NCE (July 2020) + worst case generic settlement.
Zum, thanks for the article. Clearly written by PCSK9 promoters. Several observations,
1) p.5 show statins' RRR is in the teens. I bet V has better standalone RRR.
2) Surprised that statins are more efficacious for patients with no known history of CVD, probably cooking the data on the part of PCSK9 promoters.
3) 5.4% annual event rate for patients with history of CVD is in the ball park of sicker R-IT patients' estimate.
4) Why Northern Europe has so much FH? (p.15)
5) To dis-credit hypertrig., it quotes a 1991 paper (p.14).
http://www.ncbi.nlm.nih.gov/pubmed/1888927
Fibrates failed ACCORD study. I am surprised it's approved for type 2.
JL, AZN acquired Omthera in May of 2013 and Amarin announced its go it alone plan end of 2012. AZN clearly was interested in the O-3 market and must have talked to Amarin around the time it's contemplating the three possible paths.
More evidence HDL is not a good bio-marker for CVD,
http://www.forbes.com/sites/johnlamattina/2015/09/17/amgens-acquisition-of-dezima-and-cetp-drug-like-pfizers-03-buy-of-esperion-will-history-repeat/
"Pfizer ran a cardiovascular outcomes trial (CVOT) comparing torcetrapib + Lipitor to Lipitor alone in order to demonstrate that the unprecedented LDL-cholesterol (LDL-C) lowering and HDL-C effects of the combination translated to far fewer heart attacks and strokes than seen with Lipitor alone. Shockingly, this CVOT, known as ILLUMINATE, showed that the combination was inferior to Lipitor alone."
So I think Kiwi's worry of R-IT not having enough patients with low HDL is misplaced.
STS, do you take into account that the 1g of EPA/DHA pill in Sears' table contains less than 600mg of EPA?
STS, thanks for the real world feedback on your ratio. Based on Dr. Sears' ratio table, I would have expected a bigger drop on your ratio after 4g/day of V but I guess each individual is different.
In US, Kowa has its own sales force and has nothing to do with TEVA.
It’s Complicated! Large Genetic Study Of Coronary Disease Shows How Much We Don’t Know,
http://cardiobrief.org/2015/09/08/its-complicated-large-genetic-study-of-coronary-disease-shows-how-much-we-dont-know/
"Which risk factors matter most for CAD? Unbiased genetic survey finds only LDL, Lp(a), TG, & SBP."
I have posted it before but worth another posting on a down day.
Larry Huston and his Skeptical Cardiologist friend are spreading scare tactic on Vascepa directly. Anybody with freshman chemistry knowledge should understand such basic chemical reaction between fish oil and polystyrene. Larry should make a good whistleblower should he be caught with his pants down one day.
AK, the effect of low HDL on MACE events may not be as important as you think:
1) p.5 of Amarin Sept. presentation, http://files.shareholder.com/downloads/AMRN/4050598323x0x799267/B882FB49-4910-4F4D-9534-301ED99C78ED/Amarin_Investor_Presentation_sept_2015.pdf
2) Multiple genetic studies
3) Failed ACCORD, AIM-HIGH and HPS2-THRIVE trials
4) Table 1 of the FIELD trial I mentioned earlier.
Suppose the effect of low HDL on MACE is indeed minimal, however nearly all subgroup analysis of high TG and low HDL has the opposite effect. What does that tell you about the effect of high TG on MACE?
Thanks HD. I do remember JL's commentary on this topic few months ago. The AA level of R-IT patients remain an unsolved mystery which could determine the R-IT vascepa arm event rate. From Dr. Sears AA/EPA ratio table, 7.5g of EPA/DHA pill (about 4g EPA?) drops the ratio from 12.1 to 1.2. R-IT patients could be very inflamed and their ratio might be over 20 (?). So 4g of pure EPA might only drop the ratio to 2.0 or higher (?), hence the Vascepa arm event rate could be higher than JL's prediction of as low as 2.2% (I might quote JL incorrectly here). I also don't know the effect of max dose statin on AA/EPA ratio so there are lots of variables to consider in this R-IT puzzle. I just want to put this out so that smart posters like you and JL may want to comment further.
Kiwi, thanks for reading my post. If you look at table 1 of the link, under prior CVD column, the 5-yr event rate for raised TG is 29.3% while the 5-yr event rate for raised TG and low HDL is 29.8% (data near the bottom of the table), i.e., pretty negligible difference over a 5-yr span.
Dr. Sears' comments on AA/EPA ratio,
http://www.drsears.com/resources/cellular-inflammation-testing/
"The JELIS study was one of the largest cardiovascular studies ever done using more than 18,000 subjects with elevated cholesterol levels. When these subjects were given high doses of EPA (1.8 grams of EPA per day), their average AA/EPA ratio decreased from 1.6 to 0.8. This reduction in the AA/EPA ratio was associated with an additional 19% reduction in cardiovascular events during the next four and half years"
"A recent study from Italy has demonstrated that the AA/EPA ratio is always greater than 15 in patients with chronic diseases (1)."
If the R-IT patients have a AA/EPA ratio of over 15 (but we don't know the effect of high dose statin on AA/EPA ratio), then 4g of pure EPA will probably bring the AA/EPA ratio to a very low level (smart posters are welcome to quantify it).
BB, HD said R-IT's probability of success is 100% but probability of stop at interim is 80%.
Interesting insight from the FIELD trial: HDL level doesn't matter (confirm with multiple independent genetic studies), i.e., event rate for high TG/low HDL is more or less the same as high TG alone. See Table 1 of the following link,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646035/#r13
I particularly like the following conclusion,
"Marked hypertriglyceridemia (≥2.3 mmol/l) with or without a low HDL cholesterol level was associated with a higher CVD risk than meeting the criteria for metabolic syndrome, supporting a continuous positive relationship between triglyceride levels and CVD (13). This level of hypertriglyceridemia was associated with increased CVD events in earlier studies (8,14), presumably reflecting a tendency for high nonfasting triglyceride levels and higher numbers of remnant particles and may be associated with more extreme abnormalities in other biological processes (such as oxidative stress, inflammation, and hypercoagulability), leading to more aggressive atherosclerosis (12,14,15)."
I think Amarin derives the 5.9% R-IT placebo group event rate from Table 1.
The BIP study is listed in Amarin Sept's presentation (p.10). Here is the link for the BIP study,
http://circ.ahajournals.org/content/102/1/21.long
" Among patients with baseline triglycerides ≥200 mg/dL (225 patients in the placebo group and 234 in the bezafibrate group), bezafibrate reduced the cumulative probability of a primary end point by 39.5% (P=0.02), "
"Although the overall effect of bezafibrate on the incidence of primary end points was moderate (P=0.24), the reduction in the primary end point was impressive in the subgroup of patients with high baseline triglycerides (≥200 mg/dL)."
One should go thru all studies mentioned, time permitting, on that p.10 to confirm or deny R-IT's chance of success.
I am puzzled that there is no stand alone US/EU trig. trial ever. Please let me know if you find any.
HD,so R-IT has a 100% probability of providing at least 15% RRR when combining with statin while JL said it's at least 98% probability. That's from the two smartest posters on this board. The market right now gives R-IT at less than 25% probability of success which is fine with me. The market is not always efficient, especially for a left for dead stock (due to FDA's unfair treatment) like Amarin.
Based on my 20-yr trading experience (much less than JL), a left for dead stock that defies all odds and survive is where you make your big money. In 2009, I invested $1M in a left for dead stock "GGWPQ" @ an average cost of $1 and sold it two years later @ over $22, by following Bill Ackman's advice. The Baker Brothers, HD and JL are as smart as Bill Ackman, IMO.
Thanks Sam. I am very impressed with the ATH in NRx, +22% from previous week Vs +10% for G.L. 1A effect barely started and it's already quite obvious. Over 14K script next week.
Zum, thanks for the Dr. Bhatt article. I agree with the following regarding trig:
"because you could say in a mendelian randomization trial—that is, nature's clinical trials—the people who carry genes that are associated with low LDL-C do seem to have lower cardiovascular event rates.
Those sorts of mendelian randomization studies that have been positive for LDL-C—for that matter, this is also the case with triglyceride levels—have not been positive for HDL-C, at least not for the genotypes studied to date.
That makes me think that LDL-C, and hopefully triglycerides, aren't just risk factors, but are modifiable risk factors—that is, they're really causal, not just associative. "
Drrc, do you realize the market and especially the biotech sector is very weak lately? On the contrary to your opinion, I think AMRN is holding up exceedingly well.
From your link of the Jardiance trial,
"After a median follow-up of about three years, about 10.5 percent of those getting Jardiance had suffered a heart attack or a stroke, or had died from cardiovascular causes, compared with 12.1 percent of those getting a placebo. That works out to about a 14 percent relative reduction in risk."
R-IT's events include soft MACE, therfore R-IT placebo group's annual event rate of over 5.2% seems very achievable.
Zum, the fact it under performs Generic L by so much is disappointing. I guess your theory of inferior quality of generic L affecting lipid results was just a rumor.
Unusually strong after hour bid @$2.49. Blue sky ahead, IMO.
A Premature SPRINT To The Finish Line,
http://cardiobrief.org/2015/09/14/a-premature-sprint-to-the-finish-line/
Study Showing Need For Low Blood Pressure Lauded But Push To Lower Cholesterol Levels Vilified,
http://www.forbes.com/sites/johnlamattina/2015/09/13/study-showing-need-for-low-blood-pressure-lauded-but-push-to-lower-cholesterol-levels-vilified/
One, you might be right but normally sponsor appeals before the issuance of CRL.
HD, if my estimation is correct, the 50% interim look, if any, could happen any day now. Is that right?
Labor Union Targets American Heart Association For Financial Conflicts
http://cardiobrief.org/2015/08/26/labor-union-targets-american-heart-association-for-financial-conflicts/
Zip, would you please revise your post in light of the PCSK9 situation?
"Politics and the FDA. The FDA was worried at the Adcom that millions of people would be treated with Vascepa and hitherto unknown side effects might show up. I have noted the the FDA is especially sensitive to side effects when large populations are in line to be treated. It is safer for the FDA to disapprove of a drug which might have benefits than to approve of a drug which might do harm. The FDA is especially sensitive to criticism and although it it may get criticized for both approvals and disapprovals, the latter seem to be much worse. The fact that Vascepa has been used on 8000 plus patients without side effects may assuage some of the FDA's fears. "
IMPROVE-IT Substudy: Ezetimibe Benefit Restricted To Diabetics,
http://cardiobrief.org/2015/08/31/improve-it-substudy-ezetimibe-benefit-restricted-to-diabetics/