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I understand your hypothetical. However much like JT couldn’t comment on not getting a label I cannot comment on value of a scenario that isn’t even a possibility IMO. Sorry. Best of luck.
This is not even up for consideration. There’s not a scenario we don’t at least get the ADA (level A) recommendation within our label. Postulating differently is a waste of time. Other labels you can question but we will 100 percent get the DM plus CV risk factor (primary prevention) on label. My opinion. Your welcome to disagree but I keep seeing this posted.
MRC
I thought MRC had some basic medical knowledge but I came across some recent posts and I am surprised so I thought I would educate him and anyone else that has unfortunately came across his posts.
MRC tries to point out that our pop is “small” or “smaller than repatha.” However, there’s many points he should be aware of.
The NNT for repatha at 67 vs NNT for Vascepa is 21. Vascepa is MORE than three times better. Physicians care a lot about the number needed to treat and very simply a low NNT will translate into ease of market penetration (Vascepa >>>Repatha). It matters 1) if your market size is big but 2) if you can capture it. MRC probably doesn’t know that because he is misinformed on most of his information (at least all of his medical knowledge but more recently he was completely inaccurate from a law perspective as Amrn’s opposing law firm’s own expert witness didn’t support their claims as pointed out by ORT, slam dunk).
MRC states that our target population is small. This really demonstrates the tremendous lack of medical knowledge or really degree of research he has done. This is completely false even with the lowest tier label which would be similar to the ADA guidelines. The ADA standard of care is the minimum label we would be offered. There’s no situation put forth that would be a “small population.” To add, we can very likely get a label without statins, without a TG level etc. MRC is very likely not familiar with off label usage as well which is not counted in any analyst price target or peak sales estimates; however, they will account for a tremendous amount of Vascepa sales regardless of label. In fact to date, our off label usage has been higher than on label for Vascepa currently. Vascepa will surpass Lipitor in billion dollar peak sales. Much like everyone in the world takes a baby aspirin (yet there’s no indication for it in a large number of them). Vascepa will be similar because the trial data is beyond conclusive and it will be extrapolated out to the masses.
Note : we will target the majority of the below “small population” with an ADA like label and get the rest of the market through off label usage which is VERY COMMON practice in medicine.
38M patients in U.S. are on statin therapy
> 25% of adults in U.S. have CV risk factors beyond LDL-C (e.g. ~50M to 70M adults in U.S. have elevated triglycerides levels >150 mg/dL)
Agree. I’m glad he pointed this out. It’s a shame many don’t know this.
This is a great post raf and also the reason primary prevention for DM patients will definitely be on the label without a doubt.
Yes. No doubter.
Worst TG > 150 on statins
Best TG> 135 with or without a statin.
I don’t think we can get a label for no TG level requirement
try most of these references 24 to 40. I looked through only a few but amrn references those.
the mineral oil issue is a dead issue for multiple reasons
1) the placebo group with higher LDL cholesterol did worse
2) Multiple studies show the rise and even worsening rise in LDL in placebo groups. Thus it is not from the placebo chosen
3) Our 2013 ADCOM had NOT one voter vote against us due to the mineral oil issue. None.
5) ADA provided us standard of care and had no mention of our results being confounded. This will be relied upon heavily at the ADCOM as it makes 0 sense to not provide a label to a drug that is standard of care. That’s a massive problem for physicians and not the goal of an ADCOM. Additionally adcoms cannot force amrn to run a trial (they stated this in their 2013 Adcom) and thus they have to grant the label and if someone later runs a proper trial to put this issue to bed then that’s on them. An option is not label pending a phase 4 trial.
4) Jelis showed 19 percent RRR so we have an outside study providing further scientific evidence our study was not confounded.
It’s a massively one sided argument.
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18 Tsalamandris C, Panagiotopoulos S, Allen TJ, Waldrip L, Van Gaal B, Goodall I, Jerums G. Long-term intraindividual variability of serum lipids in patients with type I and type II diabetes. J Diabetes Complications. 1998 Jul-Aug;12(4):208-14.
19 Dayspring, T. Lipidaholics Anonymous Case 291 Can losing weight worsen lipids? On Lecturepa (http://www.lecturepad.org/index.php/lipidaholicsanaonymous/1140-lipidaholics-anonymous-case-291-can- losing-weight-worsen-lipids).
20 Reed RG, Kris-Etherton P, Stewart PW, Pearson TA. Variation of lipids and lipoproteins in premenopausal women compared with men and postmenopausal women. DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) Investigators. Metabolism. 2000 Sep;49(9):1101-5.
21 Nazir DJ, Roberts RS, Hill SA, McQueen MJ. Monthly intra-individual variation in lipids over a 1-year period in 22 normal subjects. Clin Biochem. 1999 Jul;32(5):381-9.)
22 Sathyapalan T, Atkin SL, Kilpatrick ES. Variability of lipids in patients with Type 2 diabetes taking statin treatment: implications for target setting. Diabet Med. 2008 Aug;25(8):909-15.
23 Sathyapalan T, Atkin SL, Kilpatrick ES. Low density lipoprotein-cholesterol variability in patients with type 2 diabetes taking atorvastatin compared to simvastatin: justification for direct measurement? Diabetes Obes Metab. 2010 Jun;12(6):540-4.
24 ODYSSEY: Schwartz GG, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl
J Med 2018 [epub ahead of print].
25 AURORA: Fellstrom BC et al. Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis. N Engl J Med 2009;360:1395-407.
26 CARDS: Calhoun HM et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicenter randomised placebo-controlled trial. Lancet 2004; 364: 685–96.
27 dalOUTCOMES: Schwartz GG et al. Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome. N Engl J Med 2012;367:2089-99.
28 DESCARTES: Blown DJ et al. A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia. N Engl J Med 2014;370:1809-19.
29 HOPE-3: Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med 2016;374:2021-31.
30 IMPROVE-IT: Cannon CP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes .N Engl J Med 2015;372(25):2387-97.
31 ODYSSEY-COMBOII: Cannon CP et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J 2015 May 14;36(19):1186-94
32 PROVE-IT: Cannon CP et al. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med 2004;350:1495-504.
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33 SHARP: Baigent C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomized placebo-controlled trial. Lancet 2011; 377: 2181–92.
34 SPARCL: Amarenco P et al. High-Dose Atorvastatin after Stroke or Transient Ischemic Attack. N Engl J Med 2006;355:549-59.
35 TNT: LaRosa JC et al. Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. N Engl J Med 2005;352:1425-35.
36 ILLUSTRATE: Nissen SE et al. Effect of Torcetrapib on the Progression of Coronary Atherosclerosis. N Engl J Med 2007;356:1304-16.
37 ASCOT: Sever PS et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicenter randomised controlled trial. Lancet 2003; 361: 1149–58.
38 ANACETRAPIB (REVEAL): Bowman et al. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med 2017;377:1217-27.
39 SEAS: Rossebo et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. N Engl J Med 2008;359:1343-56.
40 ACCELERATE: Lincoff AM et al. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease. N Engl J Med 2017;376:1933-42.
41 SEARCH study: Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage J, Bowman L, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Peto R, Collins R. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010 Nov 13;376(9753):1658-69.
42 Yamamoto A, Yokoyama S, Yamamura T. Escape phenomenon occurs by lowering cholesterol with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor in patients with familial hypercholesterolemia. Atherosclerosis. 1988 Jun;71(2-3):257-60.
43 Masterjohn, C. (2011 April 11). How a Study Can Show Something to Be True When It’s Completely False — Regression to the Mean [Web log post]. Retrieved from https://chrismasterjohnphd.com/2011/04/01/how-study- can-show-something-to-be-true.
44 Glasziou PP, Irwig L, Heritier S, Simes RJ, Tonkin A; LIPID Study Investigators. Monitoring cholesterol levels: measurement error or true change? Ann Intern Med. 2008 May 6;148(9):656-61.
45 Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia N Engl J Med. 2019;380:11-22.
46 M. Yokoyama, et al., Effects of eicosapentaenoic acid on major coronary events in hypercholesterolemia patients (JELIS): a randomized open-label, blinded endpoint analysis, Lancet 2007; 369:1090-98.
47 Saito Y, Yokoyama M, Origasa H, et al; for JELIS investigators, Japan. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200(1):135-140.
48 Matsuzaki M, Yokoyama M, Saito Y, et al; for JELIS investigators, Japan. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease. Circ J. 2009;73(7):1283-1290. 49 T. Watanabe, K. Ando, H. Daidoji, et al., CHERRY study investigators. A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins. Journal of Cardiology. 2017;70:537-544. 50 Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72(3):330-343.
51 Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. Atherosclerosis. 2015;242(1):357-366.
52 Nelson JR, Wani O, May HT, et al. Potential benefits of eicosapentaenoic acid on atherosclerotic plaques. Vascul Pharmacol. 2017;91:1–9.
53 Mason RP, Dawoud H, Jacob RF, et al. Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin. Biomed Pharmacother. 2018;103:1231- 1237.
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54 Takamura M, Kurokawa K, Ootsuji H, et al. Long-term administration of eicosapentaenoic acid improves post- myocardial infarction cardiac remodeling in mice by regulating macrophage polarization. J Am Heart Assoc. 2017;6(2). pii: e004560.
U would think then he would know not to do this again against amrn but I suspect he didn’t learn.
Agree it’s just diff today the it was then. Listening back, they were all
Focused on all the TG Lowering therapy trials that failed leading up to the anchor adcom. Therefore even tho anchor showed reduction in TG, no one wanted to commit to saying that the TG reduction will lead to CV reduction. We know today the vast majority if not all of CV reduction we obtained is not due to the TG reduction so this seems like a slam dunk approval to be quite honest. We are beyond a TG lowering therapy and we proved everything asked of us and more. There’s just about no way we don’t get approved when you go back and listen to why the 9 people did not vote in our favor. Plus as you mentioned we have NEJM, ADA standard of care and Bhatt behind us. Period. Stay strong longs.
Amrn adcom 2013 videos. Idk if anyone has posted this lately or seen it but I rewatched some particularly the last video. Surprisingly very bullish (my memory didn’t remember some of these points that were made). Watch the afternoon session video. Many advocate for approval back then and then some comments on if you run the trial and it’s positive then it’s an easy approval vs giving a label now (for anchor) and if trial negative then it’s a long process to pull the label so obviously they went with option 1. And guess what reduce it was over whelmingly positive.
I honestly see us getting the label at 99 percent chance. Yes I have read all the MRC posts. The data is too strong for no label. I look forward to Nov 14 adcom and in mean time I’ll hope for a miracle burn shorts and shoot stock price up. miracles do happen.
What happends if these people can’t make it. Do they change the date further back?
It’s bc of the label. The label isn’t straight forward. That’s what we have to believe.
My take
Obviously disappointing today but fundamentally nothing has changed. If you were buying on any and all drops you should be buying here. We all have a lot riding on this but our DD has been extensive. Probably the most extensive of any board in biotech. I take this as a delay with a bullish twist as now I’m looking for a bigger label than originally thought (no statin needed or possible but less likely TG value not on label). Either way we are getting approved and going to be blockbuster.
I also do not see that JT knew this was going to happen this late. I know conspiracy theories are out there but he was fairly clear in his 8 K.
I spoke with my lawyer friend who reiterated the fda many times tries to restrict the release and that is completely legal. I don’t see the fda as trying to fuck us except that they are incompetent and should have requested an adcom at the start. Additionally, they did grant us priority review if you remember which helped ease some tension in longs who have no trust for the fda.
Last point, just when you think there’s no catalysts and we are in a downtrend, one will spring up and as quick as it went down it can spring back up. I look forward to seeing the adcom review questions and know we are getting a label when the time comes. Hang in there all.
Nov 14th will be here soon and remember the stock price will likely have a big reaction on Nov 14 not on the actual pdufa date.
Good luck and thanks to the many on this board that contribute daily to the great DD.
No adcom and 99 percent lock on label (nothing is 100 percent).
I’m wondering if we can get a label that is not dependent on having a statin. Not necessary but would be a big gift. I’m surprised JT alluded to it in the last conf call. I’m ultra bullish for q4. Going to be too many catalysts to hold this down any longer. 30 + by end of 2019.
Bought more Jan 2020 call options.
No. Once the label comes in we move upward. Over 20. 20-25 if it happends right now as we sit at 16.70. From there, catalyst after catalyst with no longer that fda overhang from our prior CRL so we will move upward much like we did after reduce it was positive and we continued to go up and up.
Bought more sub 17. I can’t say I can predict the bottom by any means but looking a few months ahead these prices will be in rear view mirror.
This is potentially massive if this is accurate. I’m surprised they wrote “very soon” and not just “soon.” This could be that catalyst that destroys the shorts. I hope it’s prior to label.
No shot. JT said they haven’t discussed details of label yet and that may happen 1 month before.
Nice info. However it’s hard to compare the two because Vascepa has been approved already so it’s a diff trajectory. Additionally today’s market you can argue is easier to penetrate with the advances in social media since then. Lastly, I believe the Vascepa market is actually bigger than the statin market because of less side effects and I think it will have more off label use given TG <150 and > 150 enjoyed reduction in Mace.
For me 2020 guidance is a key number many will be looking at. We may get some insight into that number when JT provides a max supply update that he said he would state towards the end of this year
Yeah I mean q4. After label sometime in Nov maybe a 2020 guidance update.
If JT doesn’t give us a guidance update for 2020 to be > 1 B, I’ll be exiting out of extreme frustration alone. There’s absolutely NO reason we can’t hit 1 B in 2020. JT is going to make it happen.
It doesn’t matter. It’s still a point to know about to be well Informed. You have to know all the competition.
Even if a drug performs worse it will still take X of market share. It all comes down to marketing. Good news for amrn is the market is massive so we can afford to lose a percent of market share to competition because we have a first to launch advantage and our drug will probably be the most superior.
Well said. It’s more the aftermath of the label. Once we get greenlight from label a number of catalysts stand before us and I see us running up significantly.
This is helpful. Qs is how many sales reps did humira have at peak? I still think 800 isn’t enough based on how big this market opportunity is but it’s a good kickoff.
Agree wont be a surprise to amrn but to everyone else yes
Icer - Does anyone know what info we get from ICER on draft verses full report in Sept? Will we actually know the cost effectiveness numbers this week?
Thanks all.
Stay strong. Lots of catalysts ahead.
Yeah that was debunked awhile ago At least over 5 years ago maybe more. Also as you may know , many practicing physicians still don’t know this and hospital protocols still have nursing asking about shellfish allergies prior to giving IV contrast. ha. Crazy.
Bhatt tweet.
For any fellow physicians having trouble see below.
If the issue is preauthorization, an approach that has been successful is sending in the NEJM paper and also the ADA 2019 guideline update, which specifically says no to niacin, fibrates, and supplements and gives a Level A rec to icosapent ethyl for both primary and secondary.
I hope your right and we go to 29.91 but I do have to recall you bailing on amrn weeks up to reduce it due to charting telling you it was bearish. I assume you missed the pop. Amrn was hard to predict with charts then and probably the same is true now.
No hedge. All in. Thanks for your advice but Amrn bulls ride or die as we have been since 3 bucks.
-Long and strong.
This is one of the best reads in weeks. Massive news. Thanks for bringing it to IHub. China is on no ones radar.
the reason for slow uptake was best stated by whoever posted the figure of early adopters and late adopters and where amrn is on that. That’s how it works with physicians. It’s not until the front runners adopt it and many conferences keep lecturing about it and the label is granted etc that physicians adopt a new drug.
All in all things are going great for amrn but it takes massive marketing to get the ball rolling and then it’ll hockey stick.
I see those numbers as being just a negligible difference. Won’t matter.
NO TG would be much higher. We don’t need that with the millions of Americans we can already target. Obviously that would be amazing to have No TG but I see no way to get a label of No TG without an adcom.
I see TG > 135 as most likely label.
How can amrn get 5 billion it’s first year when PfiZer couldn’t even get that. I am open to being shocked but it’s not realistic at all. They need massive expansion just to get 1-2 billion which I think would be a great 2020. Will see.
I’m suprised anyone would be short the stock. Your comments make me buy more knowing that somehow there’s still less intelligent people out there shorting this stock. Amazing to me but good for a short squeeze.
Let’s look at a snap shot of this boards track record.
Marine check
Anchor check
Reduce it check (and you and the rest of the world were wrong)
priority review check
No adcom check. Once July 10th comes you can admit to the board how wrong you are as you stated it would likely happen by then.
LDL cholesterol.
From a medical blog/website I follow. Decent info on lack of statin benefit in PRIMARY prevention. Many of us have discussed this on the board but for those that want to see more.
LDL-C Does Not Cause Cardiovascular Disease: A Comprehensive Review Of The Current Literature. Ravnskov et al. Expert Rev Clin Pharmacol. 2018 Oct;11(10):959-970. doi: 10.1080/17512433.2018.1519391. Epub 2018 Oct 11.
SUMMARY
The hypothesis that high cholesterol and specifically LDL is the major factor in atherosclerosis and cardiovascular disease and that statins has a patient-oriented positive impact has existed for decades. More evidence is being published questioning this hypothesis. These multinational authors were motivated to write this review because of three published reviews that were recently written by statin advocates.
Some of their myth busting evidence included:
No association between total cholesterol and degree of atherosclerosis
The 30-year follow-up Framingham Heart Study showed that for every 1 mg/dl drop in total cholesterol per year, there was an eleven percent increase in coronary and total mortality.
Four studies have shown a lack of association between high LDL and atherosclerosis
Study of ~140,000 AMI patients in USA showed that when they were admitted for AMI they had normal or low LDL. The patients had their LDL lowered and those with LDL below 105 mg/dl had twice the total mortality.
SR of 19 cohort studies (n > 68,000) showed that people with the highest LDL levels lived longer than those on statins.
There have been small studies that show a statistically significant benefit in MACE from statins therapy, but it is unclear if it is due to LDL lowering.
The benefits have been exaggerated by using relative risk reduction. The absolute risk reduction for total mortality is 0.4% (NNT 250)
In contrast the harms (ex: myopathy and diabetes) has been minimized.
The website TheNNT gives statins a red light (no benefit) for statins for primary prevention.
PMID: 30198808
EDITOR'S COMMENTARY - Ken Milne MD
The cholesterol and cardiovascular disease hypothesis is complicated. This review provides counter balance to half a century of promoting something that may not be true. They make good arguments that should make us question our current practice.
BOTTOM LINE: Routine use of cholesterol lower medications cannot be recommended for primary prevention while the evidence supporting statin use for secondary prevention is stronger.
In addition this site NNT is great for showing number needed to treat and to harm for many drugs. See link.
http://www.thennt.com/nnt/statins-for-heart-disease-prevention-without-prior-heart-disease-2/