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now up $3 on 500k
Up over $2 on 300k shares already
Now we know why AMRN has been so confident.
Tks Sam! Wow no monsters in here. Merry Christmas everyone!
2 days before ADCO: stock will jump to the upside if there are no major surprises in briefing documents. From the conf call it appears the company doesn’t expect any
Jesse, DC'd my statin because it caused my knee to swell. Ortho said I had arthritis so he drained it and injected steroid. I restarted simvastatin and it started swelling again in less than one week. Stopped the simva and my knee returned to normal within a week. Yes I'm an old guy not tolerate to statins.
Annual MD visit today: Told my PCP that I had to stop taking the statin (muscle and joint pain) and asked him for Vascepa. I've known him for 30 years and was surprised that he knew all about V. He said your triglycerides are good but LDLs are elevated. He said V is a powerful drug with strong results. He had no problem trying V and prescribed a 6 month supply. We'll test again after 6 months. I don't expect my LDLs to go down much so I plan to discuss Reduce-It results with him and the fact that even patients with Triglycerides less than 100 benefit from it.
RVX Fails: another one bites the dust
its obvious MRC is full of S*it
If EVAPORATE was stopped for EFFICACY then BP bids for AMRN will be coming soon IMO. They cannot wait for this to become public knowledge..
OT: Interesting PR from BCT on Breast cancer treatment
Good news about a significant event is moving PPS up
Jefferies: $410M rev could be conservative
Scripts for Vascepa continue to demonstrate double digit Q/Q growth. Total and new prescriptions are growing at ~14% and ~10%, respectively in Q3. Script data suggests Q3 sales could be tracking to $120M, give or take some inventory build, which remains above consensus of about $110M. We assume 2019 sales of $410M, in-line with consensus and towards the higher-end of $380-420M guidance, although this could be conservative given the recent script trends.
Form 4 - JT
From IV Board
In response to msg 4754 by CHM_760 view thread
Re: Form 4 - John Thero
If he does not sell the shares, this should be viewed as a bullish development, imo.
These are long-dated (2024-2025) options that were exercised. He did not have to exercise them now. But by doing so, he incurs a double hit.
First, he is out of pocket what he had to pay for the exercise, roughly $300k. (He can afford it, no doubt.)
Next, he has to recognize as ordinary income, this year, the difference between the market value of the shares purchased on the date of purchase and his exercise price. That will result in reportable ordinary income of about $2,781,500 (if my math is correct).
Why would he spend $300k, and take on an additional tax liability, now?
In most situations like this, it is because the executive anticipates a significant rise in pps in the near term. If he is right (if there is a rise in pps), he minimizes his ordinary income tax burden vs. what it would be if he were to exercise the options later, when the pps is higher.
Further, he sets his basis for capital gains taxation at the lower price (market value on the date of exercise) vs. a later higher price (presuming the pps rises), with the hypothetical difference otherwise being taxed at ordinary rates were he instead to exercise later at a higher pps.
Finally, he starts the one year capital gains holding period for the shares purchased on the date of exercise/purchase, rather than doing so later.
Conversely, were he to think the pps is likely to decline, he would not do this exercise early and hold.
All just in my opinion.
Yet another Very Positive Peer Reviewed article. For those unfamiliar with how MDs incorporate new study information into practice, this is how it’s done. It’s very similar to rolling a snowball downhill and as you can see V is picking up speed
Excellent post Mellow
BEST Post Ever on MO: 208014
Thank you AVII! MO issue is totally debunked!!
MO: A must read from Amarin
What is Amarin’s perspective on the use of mineral oil in its clinical trials and the variability commonly observed in blood-based lipid values in clinical trials of statin-stabilized patients (updated November 23, 2018)?
Overview
A placebo comprised of light liquid paraffin oil, or mineral oil, was used in the MARINE, ANCHOR and REDUCE-IT clinical trials of Vascepa. Mineral oil was selected as the appropriate placebo to mimic the color and consistency of Vascepa. Each of the three Vascepa clinical trials was conducted under a special protocol agreement, or SPA, with FDA in which FDA agreed to the use of mineral oil as an acceptable placebo. A SPA is an evaluation by the FDA of a protocol with the goal of reaching an agreement that the trial protocol design, clinical endpoints, and statistical analyses are acceptable to support regulatory approval of the drug product candidate with respect to effectiveness and safety for the indication studied.
Consistent with conclusions from two prior FDA reviews of Vascepa clinical trials, no strong evidence for biological activity of the mineral oil placebo was found by the REDUCE-IT cardiovascular outcomes trial independent Data Monitoring Committee, or DMC. The DMC was requested by FDA to examine unblinded data on an ongoing basis over a period of several years and to specifically look for a signal of biological activity from the mineral oil placebo. The DMC noted variation in LDL-C measurements in both study arms, and considered whether or not a small physiological effect of mineral oil was possible.
However, the DMC concluded that it was not possible to determine if the LDL-C increase in the placebo arm was due to the mineral oil or other factors. Increased lipid parameter levels have been observed in multiple clinical trials similar to REDUCE-IT. It is, in fact, generally understood that variability in blood- based lipid, lipoprotein and inflammation values is a common occurrence in clinical studies of statin- stabilized patients, and many long-term studies of statin-stabilized patients have observed increases in biomarkers with time, including LDL-C. Factors cited as potentially contributing to this circumstance include decreased drug and lifestyle regimen compliance, physiological compensation for drug-induced lipid changes, regression to the mean, intraindividual variability, lab variability, genetics, metabolic state, disease state, age, and season. The DMC examined whether variation in the placebo arm might have affected outcomes, found no such effect, and concluded that the small LDL-C change was not likely to explain the observed benefit of Vascepa over placebo.
Finally, a post hoc analysis covered in The New England Journal of Medicine publication of REDUCE-IT results concludes that LDL-C changes observed at one year for REDUCE-IT patients within the placebo arm did not alter outcomes. The analysis shows there was no significant difference in event rates within the primary or key secondary endpoints for patients in the placebo arm that had an increase in LDL-C as compared to those with no change or a decrease in LDL-C.
Variability in Lipid Measurements Observed in Long-term Clinical Studies of Statin-stabilized Patients
Variability in blood-based lipid values is a common occurrence in clinical studies of statin-stabilized patients. For patients with elevated triglycerides, such as those enrolled in the MARINE, ANCHOR, and REDUCE-IT studies, a greater likelihood of variability within an individual’s lipid measurements (including
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LDL-C), or intraindividual variability, has been reported. For example, investigators from the AFCAPS/TexCAPS study found that approximately 10% of patients failed study screening due to an LDL-C intraindividual variability of greater than 15%.1 The average LDL-C variability for these patients ranged from approximately 23 to 29%, and they tended to have elevated triglycerides and a higher prevalence of familial coronary heart disease compared to patients with less variable LDL-C.
In fact, intraindividual variability in lipid measurements has been studied for many years, and, using LDL- C as an example, variability in healthy adults tends to range from approximately 2 to 12%.2,3,4,5,6,7,8 LDL- C variability can also be influenced by a number of generic factors, including patient level influences, such as drug regimen and dietary compliance, genetics, metabolic state, disease state, age, and season, and lab level influences such as collection procedures, sample processing, and assay
methods.9,10,11,12,13,14,15,16,17,18 In addition, much more significant fluctuations, on a magnitude of several fold increases, can result from within a single patient,19,20,21,22,23and as noted above, these variations can be of even greater magnitude in patients with elevated triglyceride levels.
Importantly, increased lipid levels have been observed in multiple clinical trials. An upward drift in LDL-C (and other lipid) levels has been commonly (although not always) observed in statin-stabilized patients across numerous studies within varying patient populations, and many have estimated LDL-C increases of at least 6% and ranging up to more than 30%.24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40 These LDL-C increases despite statin stabilization have been postulated to be due to a number of possible factors as set forth above. Such factors include a decrease in patient drug and life style compliance with time,41 physiological compensation mechanisms whereby the body attempts to counteract a statin- induced decrease in cholesterol (known as, physiological escape phenomenon),42 regression to the mean (particularly in studies with low baseline LDL-C),43 and increased intraindividual variability with time.44
The Examination of Placebo from the MARINE Study FDA Review
FDA approval of Vascepa in 2012 was based primarily on efficacy data from the MARINE trial. As part of this approval, Amarin submitted to FDA data from both the MARINE and ANCHOR trials for consistency of results and review of safety data. Consideration of external data regarding characteristics of mineral oil was also assessed by FDA before FDA’s approval. An overview of FDA assessment of MARINE clinical data was provided by FDA as follows in connection with FDA review of ANCHOR data (Note: AMR101 research code identifier for Vascepa that is used within clinical studies):
“During the review of the MARINE data, the Division noted that several lipid parameters (including TG) increased from baseline to week 12 in the placebo group, treated with mineral oil. The available literature regarding potential effects of mineral oil was considered. Similar increases in TG levels observed in the placebo groups from the Lovaza (omega-3 EE) clinical trials of hypertriglyceridemic patients were noted, and these trials did not use a mineral oil placebo.
Because no strong evidence for biological activity of mineral oil was identified, ultimately it was concluded that the between-group differences likely provided the most appropriate descriptions
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of the treatment effect of AMR101 and that whatever factor(s) led to the within-group changes over time in the placebo group were likely randomly distributed to all treatment groups. Taken together, along with the statistical robustness in primary and sensitivity analyses of AMR101 4g/day on TG lowering, the Division concluded that AMR101 4g/day is an effective TG-lowering agent for patients with severe hypertriglyceridemia. AMR101 was approved for the following treatment indication on July 26, 2012: Treatment of Severe Hypertriglyceridemia VASCEPA™ (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.”
The Examination of Placebo from the ANCHOR Study FDA review
During the October 16, 2013 public advisory committee meeting held by FDA as part of its review of our ANCHOR sNDA, a discussion was held regarding observed, nominally statistically significant changes in the placebo group from baseline of certain lipid parameters in an adverse direction, while on background statin therapy. Nevertheless, the discussion raised questions about the possibility that the mineral oil placebo in the ANCHOR trial (and then at use in the REDUCE-IT trial) might not be biologically inert and might be viewed as artificially exaggerating the clinical effect of Vascepa when measured against placebo in the ANCHOR trial. It was ultimately concluded that the between-group differences likely provided the most appropriate descriptions of the treatment effect of Vascepa and that whatever factor(s) led to the within-group changes over time in the placebo group were likely randomly distributed to all treatment groups.
In the April 27, 2015 complete response letter from FDA issued in connection with the Amarin supplemental new drug application related to the ANCHOR study, there was no suggestion by FDA of an issue with the mineral oil placebo being biologically active or interfering with the statin-treated patient population in the ANCHOR study.
From May 2015 through March 2016, in connection with the First Amendment litigation with FDA and the related settlement agreement that allowed Amarin to promote the results of the ANCHOR study, FDA did not dispute the veracity of the ANCHOR trial data or seek to require that Amarin include any qualification in our promotion to healthcare professionals of ANCHOR data related to the mineral oil placebo.
The Examination of Placebo in the REDUCE-IT Study
Early in the course of the REDUCE-IT trial, FDA directed the DMC for REDUCE-IT to periodically review unblinded lipid data to monitor for signals that the placebo might not be inert. Over several years, after each such quarterly unblinded safety analysis and review meeting, the DMC recommended to continue the REDUCE-IT study as planned. Each of these DMC recommendations was shared with FDA.
In August 2016, Amarin announced an amendment to the REDUCE-IT SPA agreement with FDA that reaffirmed FDA concurrence on key elements of the study. In this amended REDUCE-IT SPA agreement, FDA agreed that, based on the information submitted to the agency, the critical elements of the revised REDUCE-IT protocol and analysis plans adequately address the objectives necessary to support a regulatory submission.
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As published within the main presentation of the REDUCE-IT results,45 at baseline, the median LDL-C was
75.0 mg/dL. The median change in LDL-C was 3.1% (+2.0 mg/dL) for VASCEPA and 10.2% (+7.0 mg/dL) for the mineral oil placebo arm; placebo-corrected median change from baseline of -6.6% (-5.0 mg/dL; p
< 0.001) at one year. If mineral oil in the placebo might have affected statin absorption in some patients, this might have contributed to differences in outcomes between the groups. However, the relatively small differences in LDL-C levels between groups would not likely explain the 25% risk reduction observed with VASCEPA, and post hoc analyses suggested similar results for the primary and key secondary endpoints regardless of whether there was an increase in LDL-C level among the patients in the placebo group. See Figures A and B (Vascepa is referred to as icosapent ethyl in these figures).
Figures A and B
Within the data presented in the above figures, patient-by-patient differences in LDL-C levels from baseline to Year 1 included some patients with increases, some patients with decreases and others with no change in both the Vascepa arm and the placebo arm of the REDUCE-IT study. If mineral oil affected statin absorption significantly, it is reasonable to expect that such effect might be evident in all patients on placebo (i.e., if mineral oil had a definitive effect one would expect LDL-C increases would be consistently observed among patients in the placebo arm) rather than the observed mixed results that include many patients with LDL-C decreases or lack of change in LDL-C.
Other Cardiovascular Benefits Observed with Eicosapentaenoic Acid (EPA) Independent of Mineral Oil Use
Although open label, the Japan EPA Lipid Intervention Study (JELIS) previously demonstrated a 19% risk reduction with a high concentration EPA product (an ethyl EPA preparation similar to icosapent ethyl) without a placebo.46 JELIS provides supportive but not conclusive data that EPA drug therapy could
Page 5
reduce major coronary events. JELIS included 18,645 patients with hypercholesterolemia in Japan, and it showed that patients receiving a highly purified EPA drug product plus a statin had 19% fewer major coronary events after a mean of 4.6 years than those taking only a statin.
Patients treated with EPA and statin in JELIS achieved triglyceride levels that were only 5% lower, on average, than those achieved among patients treated with statin alone; however, the reduction in cardiovascular risk in the primary endpoint analysis was 19%. Likewise, within the primary and secondary prevention sub-analyses, triglyceride levels were lowered only 5% on average in the EPA plus statin group compared with the statin alone group; however, the relative risk reduction was as follows:
• 53% in the primary prevention population with elevated triglyceride and low HDL-C levels47
• 23% in the secondary prevention population with established coronary artery disease48 Again, no placebo was used in JELIS.
In connection with FDA regulatory review of Vascepa, JELIS results led Amarin to request that FDA consider whether the cardioprotective effects of EPA observed in JELIS were due not to a single mode of action, such as triglyceride lowering, but rather to multiple mechanisms working together. In regulatory dialogue with Amarin, FDA did not disagree with this possibility.
Also in Japan, the CHERRY study showed that EPA added to high dose statin doubled plaque regression vs. high dose statin therapy alone.49
Potential Mechanisms of Action
As noted in The New England Journal of Medicine:
“The observed cardiovascular benefits were similar across baseline levels of triglycerides
(<150, ≥150 to <200, and ≥200 mg per deciliter). In addition, the significantly lower risk of major adverse cardiovascular events with icosapent ethyl than with placebo appeared to occur irrespective of the attained triglyceride level at 1 year (≥150 or <150 mg per deciliter), which suggests that the cardiovascular risk reduction was not associated with attainment of a more normal triglyceride level. These observations suggest that at least some of the effect of icosapent ethyl that resulted in a lower risk of ischemic events than that with placebo may be explained by metabolic effects other than a reduction of triglyceride levels.”
The observation that at least some of the effect of icosapent ethyl that resulted in a lower risk of ischemic events may be explained by metabolic effects other than a reduction of triglyceride levels is consistent with prior interpretations of JELIS.
REDUCE-IT was designed as a cardiovascular outcomes study, and as such, determining the mechanisms responsible for the benefit shown in REDUCE-IT were not the focus of REDUCE-IT. As summarized from the primary results of REDUCE-IT in The New England Journal of Medicine, potential Vascepa mechanisms of action at work in REDUCE-IT may include triglyceride reduction, anti-thrombotic effects, antiplatelet or anticoagulant effects, membrane-stabilizing effects, effects on stabilization and/or regression of coronary plaque and inflammation reduction. Each of these potential mechanisms were
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supported by earlier stage mechanistic and other studies cited in The New England Journal of Medicine publication of REDUCE-IT results. Independent of REDUCE-IT, Amarin has worked for years to further support the REDUCE-IT thesis with published scientific findings based on various degrees of evidence that show that icosapent ethyl may interrupt the atherosclerotic processes (e.g., plaque formation and instability) by beneficially affecting cellular functions thought to contribute to atherosclerosis and cardiovascular events and by beneficially affecting lipid, lipoprotein and inflammatory
biomarkers.50,51,52,53,54
REMINDER: NEJM’s comment on MO issue
This is THE PEER REVIEW JOURNAL for medicine
38 Second, if mineral oil in the placebo affected statin absorption in some patients, this might have contributed to differences in outcomes between the groups. However, the relatively small differences in LDL cholesterol levels between the groups would not be likely to explain the 25% lower risk observed with icosapent ethyl, and a post hoc analysis suggested a similar lower risk regardless of whether there was an increase in LDL cholesterol level among the patients in the placebo group. Although JELIS was designed as an open-label study that did not use a mineral oil placebo, it showed a 19% lower risk of ischemic events with statin therapy plus EPA than with statin therapy alone.
Question: has the company published response rates for each of the statins used in the reduce it trial?
Also remember AHA update on Vascepa is due soon
ADCOM chair is an ENDO which means the new ADA Guidelines are a MAJOR BONUS going into the meeting
Cannot imagine the chair going against guidelines of his/ her peers.
Cantor: No Heartbreak Here: Selling Overdone
Cantor - AMRN: No Heartbreak Here, Negative Reaction To AdCom Is Overdone, In Our View
AMRN's announcement today that the FDA plans to hold an advisory committee meeting (AdCom), tentatively scheduled for 11/14/2019, comes as a surprise to us. That being said, we think stock weakness (-20%) in reaction to the news is overdone. The potential 3-month "extension" to the PDUFA date does not impact Vascepa's potentially multi-billion dollar peak sales opportunity, in our view, especially considering that the company originally expected it would get approval in 10 months from submission (~Jan 2020), and this extension would still get approval one month ahead of original expectations. We touched base with the company who noted that they continue to plan for success and look forward to presenting REDUCE-IT results at the AdCom.
As a reminder, AMRN originally expected an AdCom when it filed the sNDA, given the enormous addressable REDUCE-IT patient population. When we hosted meetings with management a few months ago, the general sentiment seemed to be that an AdCom could be a positive.
AMRN noted that it will continue to move forward with plans to double the size of its sales force to support the launch of Vascepa, and those hired prior to label expansion will join existing promotion efforts. We would be curious to see how much of the expansion effort has taken place so far; original expectations were to expand the U.S. sales force to ~800 by October.
Tell of the Tape: Big Boys are Buying BIG
Anticipate run back to $18 before ADCOM.
Just loaded up again. BOOOOYYYAAAAAHHHH
Jefferies says this is BUYING opportunity
Stock likely down on Adcom panel announcement and minor push-out of PDUFA date likely to end of Dec (from Sep). It's not totally surprising to have a panel although we didn't think one was likely. It's reasonable to have a drug this big discussed in public forum; hence, while there is some new risk today, we see the pullback as more than reflecting that now, and as a buying opportunity since approval is very likely, in our view. Reiterate Buy.
Insights
AMRN announced it was notified by FDA of a planned Adcom panel for the label expansion for Vascepa to include the CVOT data. The earliest the FDA could schedule a panel is Nov. 14 - hence the Sep. 28 PDUFA will be missed and it would be reasonable to have a 3-mo extension, pushing the PDUFA eventually to Dec. 28.
In the short-term, we think the stock will trade down a bit and slightly range-bound until the Street gets more comfortable on the panel topics and questions (issued two days before panel). However, while some investors might be a bit upset/frustrated since they just raised money, we think this is a buying opportunity because it's not shocking to have a panel and this should get approved and go right back up. Indeed, when a stock goes down on a panel, the expectations are reset lower. Then, when the documents and questions come out - they're not that bad - and the stock goes back up either on the questions being published showing it's OK, or on the vote for approval which relieves the fears.
In any case, this is not totally shocking although we thought on the margin, it is more likely there won't be a panel than that there will. We assume the panel topics will cover 1) overall risk/benefit for approval, 2) evidence of applicability to various patient populations (Type 2 Diabetes and/or primary prevention), 3) safety/tolerability, 4) potential to discuss the placebo arm and impact on overall results. The latter may or may not have some minor nervousness for investors, but overall, we predict the FDA will approve the drug given clearly significant (and transformative) evidence of benefit for an unmet need. In addition, the mineral oil placebo issue was discussed in the first 2013 panel and of course, it is possible it had some effect (but minor) and won't cause the drug to not be approved. Contact us for full transcripts and briefing documents from the 2013 FDA panel (and slide discussing this).
Notably, the co continues to plan to expand the salesforce (as we believe they should) and will have even more time to prepare/train in anticipation of the label expansion. We view the short-term pullback as somewhat disappointing, but also when taken into totality, believe we will look back and see this as a buying opportunity.
Company Description
Amarin Corporation
Amarin Corporation, headquartered in Dublin, Ireland and Bedminster, New Jersey is a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health. Amarin's approved drug, Vascepa, is an ultra-pure, EPA-only, omega-3 fatty acid, oral product for the treatment of severe high triglycerides and mixed dyslipidemia. The company’s cardiovascular programs capitalize on Amarin's expertise in the field of lipid science and the known therapeutic benefits of essential fatty acids in treating cardiovascular disease. AMRN reported a positive REDUCE-IT CVOT result in September 2018.
AMRN informed: 2 American Heart Assoc. reviewed NEW UPDATES
2 ACC reps(who often sync with AHA-American Heart Asscociation). "For 2019 ADA SOC, Amarin has been informed that 2 designated representatives from American College of Cardiology reviewed new updates & provided feedback on behalf of ACC consistent with the final findings $AMRN
Expect Goldman Positive Coverage soon
AMRN's ADCOM stance: was LIKELY now UNLIKELY.
So if this is correct AMRN would know the ADCOM answer and I assume they would have to issue a PR if an ADCOM is coming...correct?
ADCOM and Late Cycle Meeting: this source said the LCM will happen no later than 2 months before PDUFA. If there’s going to be an ADCOM then the date is to be moved up by at least 12 days
If this is correct then AMRN would have had their LCM more than a week ago if there’s going to be an ADCOM. Thoughts?
Go to slide 28
https://www.fda.gov/media/94069/download
Again: ICER said ‘Half of USA adults qualify for V’. Simply amazing
ICER: 'Half of USA adults eligible for V'
From ICER: “As noted in the background section of this report, approximately half of all adults in the US are affected by CVD. Consequently, a large population of individuals will likely be eligible for ongoing therapy with icosapent ethyl.”
ASPC president: REDUCE-IT is a game changer
From terrapharma
“It (REDUCE-IT) has been a game changer of a study,” Khera (ASPC President) told Cardiology Today. “We want to learn more about it and understand how we may think about applying the lessons from it in our practice.” #reduceit #icosapentethyl #vascepa $AMRN
IR confirms reason for $$ to HIT THE GROUND RUNNING
I bought hundreds of $7 strike price calls when AMRN was in the $2s and sold half then converted the remaining to shares so no I was not heavily in before the ADCOM. Of course the FDA can do anything but it's going to very hard for them to turn it down this time given the data generated by this large and successful study.
Of course anything is possible but your suggestion is very unlikely. Has the FDA ever delayed or not
Approved a drug after granting priority review?