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dited Transcript of AMRN conference call or presentation 18-Nov-19 9:30pm GMT


Amarin Corporation PLC O Webcast Discussion Of Presented Data at American Heart Assocition's 2019 Scientific Sessions

Dublin Nov 19, 2019 (Thomson StreetEvents) -- Edited Transcript of Amarin Corporation PLC conference call or presentation Monday, November 18, 2019 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants
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* Craig B. Granowitz
Amarin Corporation plc - Chief Medical Officer & Senior VP
* Elisabeth Schwartz
Amarin Corporation plc - Senior Director of IR

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Conference Call Participants
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* Deepak Bhatt
* Matthew Budoff
* William Weintraub

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Presentation
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Operator [1]
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Greetings. Welcome to the AHA investor discussion conference call. (Operator Instructions) Please note this conference is being recorded.
I would now like to turn the conference over to your host, Elisabeth Schwartz. Thank you. You may begin.
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Elisabeth Schwartz, Amarin Corporation plc - Senior Director of IR [2]
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Welcome to today's discussion to explore for our investment community the several important new data sets and analyses related to Vascepa and REDUCE-IT as presented at the 2019 American Heart Association's Scientific Sessions here in Philadelphia.
Please be aware that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements include, but are not limited to, our current expectations regarding Vascepa clinical data and cost-effectiveness analyses and expectations regarding the application of these data to clinical use, in reimbursement and regulatory settings and to commercial prospects for Vascepa. And these statements are based on information available to us today, November 18, 2019.
We may not actually meet the expectations disclosed in our forward-looking statements. Actual results or events could differ materially. We assume no obligation to update these statements as circumstances change. For additional information concerning these factors that could cause actual results to differ materially, please see the Forward-Looking Statements section and the Risk Factors section of our most recent Form 10-Q filed with the SEC.
This call is intended for investors in Amarin and is not intended to promote the use of Amarin's Vascepa outside its approved indication.
I will now turn the call over to Dr. Craig Granowitz, the Chief Medical Officer of Amarin.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [3]
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Thanks, Elisabeth, and thank you all to our panelists and listeners today for joining us. We're excited here -- to be here in Philadelphia at the conclusion of the American Heart Association's Scientific Session. We're fortunate to have 3 clinicians/researchers that are immersed in Vascepa-related sciences and have presented here at AHA to speak with us today: Doctors Matthew Budoff, Deepak Bhatt and William Weintraub. I'll give a quick recap of the presentations by each of these 3 research physicians, and then we'll move into a discussion of some of the key issues with the results.
Dr. Budoff presented this morning on the interim 9-month results of the 18-month EVAPORATE study. EVAPORATE is a first study in the U.S. to use multidetector computed tomography to evaluate the effects of icosapent ethyl as an adjunct to statin therapy on plaque characteristics in a high cardiovascular-risk population with persistently high triglyceride level. Patients underwent interim scans at 9 months and are currently being followed for an additional 9 months. Final results of this investigator-initiated study are anticipated in early 2020.
Dr. Bhatt spoke yesterday about REDUCE-IT USA. These prespecified REDUCE-IT subgroup analyses showed substantial risk reduction in the U.S. patients treated with icosapent ethyl 4 grams a day versus placebo across all predefined composite and individual primary and secondary endpoint, including a 31% relative risk reduction and a 6.5% absolute risk reduction in first occurrence of 5-point MACE. This corresponds to a number needed to treat of 15 and a significant 30% relative and 2.6% absolute risk reduction or a number needed to treat of 39 in all-cause mortality in this U.S. subgroup. I want to emphasize that these analyses of this data in the U.S. population in most studies are usually not as pronounced as what we say in the REDUCE-IT USA analysis.
Finally, we will speak to Dr. Weintraub about the preliminary analysis of the cost effectiveness of icosapent ethyl. In this combined patient level and simulation lifetime cost-effectiveness analysis, icosapent ethyl in high cardiovascular-risk patients showed an exceptional benefit with cardiovascular event reduction as well as cost savings in trial and over patients' lifetime in many simulations.
Finding of cost effectiveness of medical therapies are rare. This analysis considered the current market cost for Vascepa and the potential savings from avoiding major MACE events such as stroke and heart attack, the cost of which can often be very high. As is typical, the cost-effectiveness analysis were not prespecified as part of reducing clinical study design but did rely on the landmark results.
So Matt, I'd like to start with you. You're Professor of Medicine and Endowed Chair at the UCLA School of Medicine and Program Director of the Lundquist Institute. So Matt, if you could just give a summary of some of the key points that you wanted to convey this morning at the late-breaker. And I do want to note that you were the first on the agenda for the morning. So clearly, there was a high degree of interest in the sponsors of the session to hear what you had to say in the EVAPORATE study.
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Matthew Budoff, [4]
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Yes. And I think it was very, very well received by the physicians in the audience. Basically, we demonstrated that, over just a short 9-month analysis, that there was generally a uniform plaque regression in the patients who received Vascepa as compared to those patients who received placebo. Because it was a small number of patients, it was an 80-person trial, and we only had follow-up in 67 patients at the interim analysis, the power was a little diminished because we powered it based on an 18-month trial. But I have to say that while the primary endpoint was 21% reduced, which was not enough to stop the trial, it was very concordant with all the other parameters. For example, total plaque went down by 42% with a p-value of 0.004, and that's -- we have not seen that type of plaque stabilization or slowing of plaque progression with other therapies that we've studied, especially over a short interim time frame of only 9 months.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [5]
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Now, Matt, that's a really helpful summary. And I guess there are some questions that I've heard this morning about what does the mechanistic study actually mean, why do the study -- what -- where do you think that's going to add to the body of literature. And I'll note that Dr. Bhatt was also an investigator on this trial as well. But how, Matt, do you see this kind of fitting in? What role does this play in terms of our understanding of the field?
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Matthew Budoff, [6]
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Well, I think a lot of clinicians were surprised, to say the least, at the robustness of the REDUCE-IT study and how large the benefit was, and they want to understand better. We're telling them it's not just triglycerides, that it's not only different things, and we don't know what it is. So when you look at the primary endpoints of REDUCE-IT, all of them that could be artherosclerotic line up and show benefit. So I think it suggests that this is a direct anti-artherosclerotic benefit, but you can't derive that solely from the REDUCE-IT study. Now we can say with confidence, based on the results of EVAPORATE, that there is an anti-atherosclerotic property at play here that's supplemental to all of the other benefits that we've already seen with Vascepa.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [7]
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Dr. Bhatt, I know that there have been a number of questions asked of you, including even last week at the FDA meeting, about time to curve separation. And I think sort of putting that in context with the mechanistic results of Matt's study might be very helpful context for people to understand sort of these intermediate signals in the context of a clinical event. Could you shed some light on that?
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Deepak Bhatt, [8]
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I think that's a great question. And in the REDUCE-IT trial, we saw benefit in the 2 major cohorts, which were the patients enrolled with secondary prevention. By that, I mean stable patients with coronary artery disease or cerebrovascular disease or peripheral artery disease. As well, we saw benefits in patients who are high-risk primary prevention. By that, specifically, what we enrolled were people with diabetes and at least one other cardiovascular risk factor. So in that population of patients, there was significant benefit. The drug worked a little bit differently in terms of timing of that benefit kicking in. In the secondary prevention cohort, it looked like the curves were really starting to separate at about a year, whereas it took a couple of years in the primary prevention cohort. And that makes sense because that's what we saw in the statin trials. And in fact, if we had studied really high-risk patients, like people coming in with heart attacks or acute strokes, then I think the curves would have separated even sooner. So it really just has to do with the baseline risk.
But what I think Dr. Budoff's study has nicely done, it's done a lot of things. I mean, it's shown for those doctors that really want to see, what's the mechanism of action, if shown, will look. The plaque in the arteries looks likely to progress. So that's a really powerful visual image. But beyond that, there's another message that is a bit more subtle that, at least to my knowledge, no one has explicitly stated. This was an interim analysis. It was just 9 months. It's meant to be an 18-month study. But I'm really glad Dr. Budoff took a look, prespecified all or part of the plan that he'd laid out because it tells me that there are benefits that are kicking in early. So if you're a physician and you see the patients that we enrolled in REDUCE-IT were stable patients, again, they're not in the throes of a heart attack or that sort of patient, you're going to throw the kitchen sink at them in terms of risk reduction. They're pretty stable. They're in the office. They're not actually complaining of anything. They're doing okay. It'd be easy to just say, look, I'll see you back in a year. But the problem with that approach now we see with a REDUCE-IT-like patient that's out there in practice, their plaque is progressing in the course of that year. So this really provides an impetus for why a physician needs to pull the trigger and act sooner with respect to prescribe it.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [9]
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No, I think that's really important context. One of the other sessions I was at yesterday was talking about the effects both on the particles and on inflammation. And Matt, I don't know if you want to comment at all because that might tie into -- one of the questions I think comes up is, why are there so many endpoints that are looked at in this? What are all these different surrogates of total plaque and low attenuation plaque and calcified plaque? Maybe you could help give, again, some of our investors some context of what all of that means because it's just some terminology that might be confusing.
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Matthew Budoff, [10]
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Well, absolutely. So I think when we look towards therapies that have both presumed the anti-atherosclerotic effect and an anti-inflammatory effect, then we start to think about things like the low attenuation plaque, which what we think of kind of is the necrotic core, the really vulnerable plaque, that might be most likely to rupture.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [11]
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And what happens when the plaque ruptures, Matt?
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Matthew Budoff, [12]
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When a plaque ruptures, patients have an acute heart attack or an acute stroke. The artery gets occluded, and they end up with an immediate event. 1/3 of people die suddenly when these plaques rupture.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [13]
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And that really was the endpoint, right, Deepak, of REDUCE-IT? That's sort of the clinical consequence of a plaque gone bad.
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Deepak Bhatt, [14]
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Look, it's a great one-two punch when you think about EVAPORATE and REDUCE-IT. You've got basic mechanistic data now by imaging and a clinical trial that shows clear-cut benefits. So it's a really nice package scientifically. For physicians out there that want mechanism of action, now we've got one. Now there are several other mechanisms of action at play too, I think, with icosapent ethyl with the ability to retard plaque progression. That's pretty important.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [15]
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Right. So Matt, I'm sorry I interrupted you talking about some of the different endpoints of the study.
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Matthew Budoff, [16]
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Yes. So obviously, when you think about just overall progression in your coronary arteries, you would use an endpoint like total plaque, and that was very significantly reduced in the EVAPORATE trial. We focused on this more vulnerable plaque because of some of the evidence from REDUCE-IT that sudden death was reduced. So there was a signal there that maybe this plaque ruptures. There's some data from abroad, from Japan, the CHERRY study, and other studies that have also suggested that, that would be a good target to look at specifically because of a drug that has these pleiotropic or multiple effects on the vasculature.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [17]
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And I think you mentioned at least one point to me that there've been a number of these imaging studies done, mostly in Japan, not in the U.S., and that's one of the unique aspects of EVAPORATE. But has there been a difference that have been seen in the Japanese studies with different omega-3 preparations?
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Matthew Budoff, [18]
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Yes. So there's been a number of trials. There's been 2 large-scale trials, 1 in the U.S. and 1 outside the U.S., that looked at 4 grams of Lovaza without showing significant benefits.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [19]
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And Lovaza is what part of...
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Matthew Budoff, [20]
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EPA and DHA, mixed -- combination pill. And both of those trials failed to show benefit even out to 2 years. So I think this is much different than the EPA-DHA mix data that we've seen from imaging. And the Japanese data did line up very nicely with 1.8 grams of EPA. But again, Japanese populations, invasive imaging, where they're putting catheters into people's coronary arteries, things that would be really hard to emulate in the United States.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [21]
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Yes. And that's very helpful context. I think one of the other questions that people have asked me is the interim analysis threshold and the statistical benchmark for that, which seems awfully high, right? If you could talk a little bit about how the statistics might be. And I don't want to put you on the spot. I know you're not a statistician, but I'm not sure that everyone really understands that the hurdles at an interim analysis are quite high to stop a study.
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Matthew Budoff, [22]
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Yes. And basically, what you're saying is if there's overwhelming efficacy, if the drug is so good at an early time point, then you can almost argue it's unethical to continue the study, just like we stop clinical trials early when there's overwhelming benefit because we don't want to keep people on placebo or keep people off of this therapy. So we didn't hit that interim analysis based on the primary endpoint that we chose. But again, had we chosen total plaque, which is a very reasonable endpoint in many trials, we would have actually stopped the trial early because total plaque came in at P 0.004, which is less than the necessary stopping parameter. So we can -- the Steering Committee can obviously take some responsibility for picking the wrong endpoint, but hindsight is 2020. But the trial is still positive, and the trial is still ongoing, so I think that it's good news. And I think based on my conversations at the American Heart Association after the presentation, many physicians feel much more comfortable now, not people who just live and die based on clinical trials but those that want to understand the mechanism, that this adds a lot to their confidence in moving forward with the use of icosapent ethyl in their practice.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [23]
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No, that's helpful. There was one other question. I know you showed a slide at the meeting today about the placebo controls, and I know you covered a tremendous amount of data very quickly on that. And this might be a point to help clarify. What was actually done? And why is it meaningful?
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Matthew Budoff, [24]
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Yes. So since the REDUCE-IT trial was published and after we started EVAPORATE, there were some questions about the mineral oil placebo that was used and whether that was contributing to harm rather than -- or offsetting some of the benefit of icosapent ethyl. We had already started EVAPORATE, so EVAPORATE was using the same mineral oil placebo that we used in REDUCE-IT. So what we did is we matched that placebo group to another group of patients who are on a different placebo, one that's made out of cellulose that everybody acknowledges is completely inert and has no adverse properties to it. And we showed that the rate of progression on patients on mineral oil was identical to the rate of progression of those patients on an inert cellulose placebo. So hopefully, laying any concerns about mineral oil being bad, rather now all the benefit is on icosapent ethyl being good.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [25]
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No, that's very helpful. And again, I just want to clarify one other point before we left for Dr. Weintraub out of the conversation. But -- so you showed a curve, and it looked like there was a 45-degree line, and there were all these dots on the curve. Maybe you can just sort of put that in context of what that meant and why did that give you comfort and confidence because I'm not sure everyone is so familiar with looking at that kind of scatter plot.
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Matthew Budoff, [26]
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Yes. No, absolutely. So this is basically just putting all of the rates of progression among both cohorts, the -- there were blue dots on the curve, if you saw it on the slide, that were represented the cellulose placebo from another randomized trial, and there were red dots that represented EVAPORATE placebo patients. And the line of identity went -- was identical for the two. In other words, we graphed out what is the rate of progression among those 2 cohorts, and they were -- the lines were superimposed.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [27]
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Right. So each one of those dots was an individual patient over that time course and sort of seeing that there was an equal distribution across both sides, which said, statistically, there was absolutely no difference in the rate of change between those 2 of the parameters you're looking at.
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Matthew Budoff, [28]
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Absolutely. And what people need to understand is when we're up there presenting, as we all do fairly frequently, there's literally a giant clock that only we can see that is counting down towards 0. And when it hit 0, you have to stop talking. So...
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [29]
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And it's flashing red so...
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Matthew Budoff, [30]
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Yes, yes. Yes, yes.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [31]
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And they turn off the microphone.
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Matthew Budoff, [32]
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But -- so we are under some time pressure. So yes, so we couldn't put in all of the data, obviously, that we would have liked to in a more open presentation. I was limited to 10 minutes to present the entire spectrum of data. But yes, that line basically shows that there's -- with all the individual data points, that there's no difference. And we did multiple analyses with all different types of plaque. And regardless of what we looked at, their rates of progression on cellulose placebo, inert placebo was identical to mineral oil placebo. And I did, I think, hopefully, to at least the scientists and the clinicians in the room, effectively convey that mineral oil, therefore, is not the bad player that some people have accused it of being.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [33]
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No, thanks. Thank you. And I think that was another important analysis that came out of the study. Bill, I wanted to turn our attention to you. We're very fortunate to have William Weintraub here from the Medstar Institute, who has a long history of doing cost effectiveness analyses as well. And Bill, you're also a cardiologist also?
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William Weintraub, [34]
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I am.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [35]
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So he's a clinical cardiologist and a health economist with a lot of publications in this particular area and really an acknowledged expert. And I give Dr. Boden and the Steering Committee a lot of credit for reaching out and engaging with Bill on the cost effectiveness that was presented here at the meeting. And again, this was done with the support of Amarin but really independent of Amarin, knowing all the sensitivities, particularly around cost effectiveness analyses.
Bill, you might want to just share just in a minute or 2 your perspective on the study and its design. And again, this was done in the overall total population, not the U.S. population. One of the reasons I wanted to go to the total population first before asking Dr. Bhatt to comment on the U.S. population is I don't want to confuse the 2 because I think having them presented at the same meeting could be potentially confusing to people. So you studied the overall REDUCE-IT population.
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William Weintraub, [36]
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Right. We did. We looked at the U.S. population too, but we started out with the total population. We used U.S. prices, but we used the total population, which is the typical way this is done. Now -- and with REDUCE-IT, we found a 25% relative risk reduction for the first or primary endpoint but 30% overall. In the cost-effective analysis, we used all events, not just the first event. So here, we have a relatively inexpensive pharmaceutical, (inaudible) pharmaceutical. And we have a remarkable reduction in event rates, 30%. This is an unusual situation.
Now what we did is we have to use a number of different costs inputs. We have to look at the cost of the drug. We used what is called SSR net pricing, which we strongly believe that's the right price to use in cost-effective analyses. We used different input values for the cost of events. We used Optum cost, which gives a very broad distribution of costs in patients under the age of 65 and Medicare costs over the age of 65 for our base-case analysis.
Then the other thing we have to look at is utility, how well patients are functioning on scale 0 to 1, with 1 being perfect health and functioning, 0 being generally mortality. We use utility values from the literature, and then we have to estimate survival. Now the remarkable thing about what we did here is that we had 5 full years of in-trial data. And with that, we could look in-trial not using a simulation, not using estimation but using real data. And with that, we found that icosapent ethyl in our base-case analysis is a dominant strategy and as we offer better outcomes at lower cost.
For (inaudible) pharmaceutical, none of us have ever seen anything quite like it before, very unusual and very important. This carried over into our long-term survival analysis as well. But there always has to be a partial simulation because we have to estimate event rates that we haven't measured. We have to estimate survival. Nonetheless, both of these work together to suggest that we have remarkably efficacious therapy, which offers great value. And at least, our preliminary results do suggest that it is dominant, that we went for better outcome at lower cost.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [37]
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Thanks, Bob. A very good summary. And again, some of the questions that I've been asked on a number of occasions, is there was an independent group called ICER, that also did an analysis. They came up with somewhat different findings, even though I think they use the same drug cost. Maybe you could talk a bit about the ICER analysis, what are the strengths and weaknesses of each one of them because ultimately, it's sort of this constellation of models that are out there, right?
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William Weintraub, [38]
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All right. So I mean, they've also found that the cost of icosapent ethyl is highly cost-effective is using most benchmarks. They did not find it to be a dominant strategy. But still, we've got a relatively remarkable incremental cost effectiveness ratio of $18,000 for quality adjusted life year gain, but still very good by almost any measure. The difference is to shift from dominant to $18,000. It's actually not that big. It sounds a lot, but it's actually a very small shift that can result in that. What do they do that was different from what we did. First of all, that was a total simulation. They did not have access to the clinical trial data.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [39]
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And so, Bill, for -- I'm sorry to interrupt, but what does that mean the simulation versus actual clinical data, because I think these are concepts, and not everyone is so familiar with.
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William Weintraub, [40]
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Well, thank you for interrupting. Allow me to clarify that. So a simulation would mean you take results of the trial. It's not that it's made up. I don't want you people to think that this is some kind of fantasy, that's not the case. What they did is they took the overall results of the trial as published in the first -- REDUCE-IT paper and then develop a mathematical model from that, that allows them to estimate the cost effectiveness. That can be -- that works pretty well, but it's not as good as having the actual data in your hands. The other thing is that there's going to be variation. We can look at the distribution of things a lot better when we have the data. So everyone understands that not all patients are the same. You have the distribution of patients. But if you only have the sort of the bottom line results, you can't look at that distribution the same way you can get all of your data.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [41]
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Now I also understand that they only looked at some of the endpoints, not all of the primary endpoints of the study as well?
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William Weintraub, [42]
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Right. So they don't have access to all of the endpoints. We have actual data. So we could look at heart failure hospitalization, AFib hospitalizations. We could look at things that they didn't have access to.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [43]
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All right. That's helpful context of how you could get the range. I think another term that isn't familiar to many, is what is dominant actually mean and how to try to understand what dominant actually would represent.
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William Weintraub, [44]
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All right. So most of the time in a cost-effective analysis for a new therapy, it'll be -- if it's effective, you'll find that it increases costs. And when that happens, you calculate as the ICER group did, you calculate what's called an incremental cost effectiveness ratio, which is generally measured in cost per quality adjusted life year gained. You don't calculate that ratio for technical reasons, you don't calculate that ratio when you have improved outcome at lower cost, improved the outcome at lower cost is called dominant. And our analysis strongly suggests that we have a dominant strategy here that has improved the outcome at low cost.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [45]
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So really, a dominant strategy today in the U.S. health care system would be what would be a fully integrated payer where they're actually paying for and bearing all of the risk, including not only the drug cost, but also the downstream bad outcomes, which is the hospitalization costs as well as the provider costs and all of the other downstream implications of the disease.
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William Weintraub, [46]
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Now what we aim at is a societal study in which we reflect everything across society, that's almost impossible to do because you can't make those pull of those measurements. So we use various proxies to allow you to get at that. But your point is this is looking broadly rather than just considering a hospital or a doctor's office or something, or something like that. So we're trying -- we aim to look as broadly across the society as we can.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [47]
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Right. And I think in our U.S. system, there are very few groups that really are tasked with or have that obligation, look at total costs. So I think probably, if the health care system is changing over time. There are more and more of those that will be both bearing the risk of all the costs as well as the economic potential gains of being able to deliver care below that cost threshold, whatever that is, whether they're reimbursed.
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William Weintraub, [48]
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Yes, that's very true. But people who do cost-effectiveness analysis, this is not uncommon for people to attempt to think as broadly as we can. But I think more and more as we consider health care economics, people are going to expect that we will own broadly.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [49]
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Now that's all very, very helpful context of this. When you said that some of the differences are subtle between the different models, what are the things that the model is most sensitive to?
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William Weintraub, [50]
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Right. So that's very important. It's most sensitive to the cost of the pharmaceutical -- there's very little difference between what we did and what the ICER did. They use SSR costs, we use SSR costs. The real difficulty is the cost of events, and there's uncertainty about what a hospitalization for heart attack or stroke for cardiac catheterization for percutaneous coronary intervention or coronary surgery costs. And because of that, that could have a big effect on the results of the analysis. And we were very sensitive to that, we'll be looking to that in very great detail.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [51]
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Now U.S. also had a unique asset that probably has not been made available very often before from commercial payers, you might want to just comment a bit on that and why those costs might be much more reflective of what is actually being paid in the real world.
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William Weintraub, [52]
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So I'm not sure what you're referring to.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [53]
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Well, you had some of the real commercial costs as opposed to the projected cost?
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William Weintraub, [54]
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Yes. Right. So you're thinking about the cost from the Optum Group?
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [55]
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Exactly.
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William Weintraub, [56]
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So Optum looks broadly across payers in the United States. And this is a huge database of -- I don't remember the exact number. But it's on the order of 160 million people in this database, broadly across payers, allowing what we believe is actually a far more accurate assessment of costs than Medicare costs. I think that people recognize that Medicare costs really do not cover the cost of events. And so if you use Medicare cost alone, you're going to underestimate the value of prevention. And so I think that's very important for people to come to understand looking at cost-effective analysis that we have to work hard to fund the best estimates of cost. And so that we can appropriately evaluate the value of the therapies that we all paid for patients.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [57]
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And since you had the patient level data, those that were less than 65 years old were not yet in Medicare, you actually use the true commercial costs. And for those that are over 65, you use the Medicare costs.
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William Weintraub, [58]
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Yes. We've done that. And I think that's relatively conservative analysis. But it can also be criticized. Well, you might say, "Oh, you should use the Optum costs for everybody." Well, what would happen then if you use Optum costs for everybody? If we think that really reflects real cost, then the finding of a dominant strategy for a cost being implemented would be strengthened even more?
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [59]
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All right. I think that's helpful context. I think these are some of the details and that are important in really trying to reflect reality what truly are the cost and risk of the global population in the U.S. group. And as you mentioned, and we'll turn it back over to Dr. Bhatt and the talk about the REDUCE-IT USA, but to look really in the U.S. population with U.S. costs might give results that are potentially different.
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William Weintraub, [60]
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So we have a subgroup analysis. We have not done this as thoroughly as we plan to in -- for the U.S., but our subgroup analysis suggests that the value of icosapent ethyl is going to be even more strengthened with -- for the U.S. patients.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [61]
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Thank you, Bill. I appreciate that. So Dr. Bhatt, I know that there was a tremendous amount of interest in doing the U.S. subgroup out of the study. What were the findings from that analysis?
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Deepak Bhatt, [62]
--------------------------------------------------------------------------------
So this was a prespecified subgroup. And the reason we were interested in looking at in the first place was to provide some context because there's a number of these large international trials, for whatever reason in the past, show results in the U.S., they're just different from the rest of the world, usually not looking as good. And then it's hard to know, is it just that it's a small subgroup, is it just a spurious finding. But then the American physician is left in the challenging position of a trial where the data might look good, but then in the wrong country, it doesn't look that good. So that was the basis for prespecifying this and the scientific rationale. So we did go ahead with this. And of course, the timing of this analysis is useful as U.S. regulators and other physicians in the U.S. are considering how to apply the data in the U.S. But the analysis itself was prespecified. So the overall results, first, let me say, for both within the U.S. and outside the U.S. look spectacular. That is for the primary efficacy endpoint, the key secondary efficacy endpoint in both cases, both within the U.S., but also in the subgroup of non-U. S. patients, both of these are statistically significantly reduced. So I don't want to create the impression that the drug is working in the U.S. and working only in the U.S. That would be a mistake. So hopefully no one walks away with that impression. The drug works globally in all the regions we studied, and there's no reason to think it wouldn't work in the regions where we didn't include patients.
Now what we found in our U.S. subgroup analysis was for the primary and key sector endpoint, results that were at least as robust, at least as large in magnitude as in the overall trial. And then on top of that, for the endpoint of all-cause mortality, a significant 30% reduction in death in the U.S. as well as that translated to a 2.6% absolute risk reduction mortality. So that is really upping the ante, so to speak, we're showing not just reductions in things like heart attack and stroke, that's pretty good and good enough, but also now showing a reduction in dying.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [63]
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Now I know the paper had a, what I would call an exhaustive review in one of the supplemental tables of all of the differences in the population. It might be very helpful for you with your clinical judgment and sort of deep immersion in the database over the last year, and maybe pick out those criteria of the U.S. subgroup that was different than the non-U. S. subgroup.
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Deepak Bhatt, [64]
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It's a great question because, again, I wouldn't want anyone in the audience walking away thinking, "Oh, the drug is, for some reason, magically just working in the U.S. and doesn't work as well outside the U.S." That's not true at all. It worked in all the populations we studied, whether it's the region, ethnicity, various other subgroups, the drug was consistent in its benefits. The reason I think the results look better in the U.S., and there's this reduction in mortality that's significant, and that the overall trial there was a trend towards a lower all-cause mortality. And mortality from cardiovascular causes and the overall trial was significantly reduced by 20%. But the reason, I think, we're seeing an amplification, you could say, a benefit in the U.S. subgroup isn't because there were people living in the U.S. per se, but rather, they had more risk factors. So I think a higher risk population, well, we saw more benefit and this is akin to what was observed in the statin literature, higher risk patients of the curves for events separate sooner, the degree of benefit is larger, but even in lower-risk patients with statins. If you follow them long enough, benefit emerges. So I think that's really the key that the U.S. patients were higher risk than the non-U. S. patients. And by higher risk, I mean, more obesity. For example, that's known from other studies, that's not a novel observation, there's more obesity in the U.S. in other regions of the world. That's unfortunate, but that's true. But there are other risk factors as well that were occurring with a higher degree of prevalence in the U.S. versus non-U. S. groups. But one other thing I'll mention, too, is that the EPA or eicosapentaenoic acid levels at baseline were a bit lower in the U.S. versus outside the U.S., so that might be another reason why it seems like the drug was performing even better than it did in the overall trial, where it performed quite well. I also want to point out, too, sometimes people have thought once they saw this data set that, "oh, maybe it's just -- there's a bunch more secondary prevention patients in the U.S.," that's really what's driving it. In fact, it's the opposite. There's a higher proportion of primary prevention patients from the U.S. So that's not what's driving it. It's just that there's more risk factors, a clustering of risk factors. So I think the take-home message isn't so much that all of the drug works there in the U.S., but rather, if you have higher risk patients, they derive even greater benefit, and that benefit kicks in sooner.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [65]
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Right. And so I think you raised what to me was a really important finding. And I think there's a lot of confusion about primary and secondary prevention in high-risk and low-risk in this perception that primary prevention is low risk and secondary prevention is high risk. The results of the REDUCE-IT USA seemed to be somewhat at odds with that common understanding or perhaps common misunderstanding?
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Deepak Bhatt, [66]
--------------------------------------------------------------------------------
Yes. The truth is this is an outdated paradigm talking about artificial universes of primary prevention and secondary prevention. And so your existing in different areas. When in fact, there's a lot of overlap. And Dr. Budoff, for example, spends a lot of his day doing CT angiography, that is imaging of hard arteries. So what is someone who is asymptomatic, but for whatever reason, they end up getting a CT angiogram, and they've got a ton of plaque in their arteries. Is that a primary prevention patient? Or is that a secondary prevention patient? That nomenclature isn't set up to capture that patient. To me, if they've got a ton of plaque in their arteries, they're at high risk. They may not know they're at high risk, they may not have symptoms or sort of an early warning system, where they're having chest pain or anything. To me, that's almost more dangerous. I'd rather have the secondary prevention patient who has stable angina. It knows when he or she's running to the bus and they're having chest pain, they stop running. But it's that asymptomatic patient, in many respects, is scarier because you don't really know what to do to reduce their risk. So it's an artificial classification. For the purposes of doing clinical trials, we enroll a bunch of different types of patients. We sort of guesstimate what their event rates might be so that we can do a trial with a particular drug or device in a finite period of time with a finite sample size. So it's a bit artificial. What we've shown in REDUCE-IT is across a variety of risk, the patients benefit substantially for icosapent ethyl.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [67]
--------------------------------------------------------------------------------
Yes. And I think, Matt, there's both a trial list, but also participating center in REDUCE-IT. I mean, what are your thoughts on this whole issue of primary prevention and secondary prevention? And when you think about the EVAPORATE study? Do you have both types of patients in EVAPORATE?
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Matthew Budoff, [68]
--------------------------------------------------------------------------------
Yes. No, I think as Dr. Bhatt already mentioned, they're not perfectly captured the way that we think of it today, but I always think of patients with a lot of atherosclerosis has, at least, what we call a secondary risk equivalent. In other words, we might not -- the guidelines may not quite put them into the secondary prevention bucket, but we treat them as aggressively as that group. And I think that's something else where EVAPORATE, I think, will help some clinicians. We're getting a lot of patients in the U.S. getting calcium scoring, which is another CT-based way of measuring risk, and we're getting a lot of patients getting CT angiography now for different reasons. And if you have a tool or a treatment that will actually help reduce the plaque burden that they see, that's yet -- going to be in their clinical eyes. Another indication to use this therapy is they use it -- I see a lot of plaque. I know this slows down plaque, I'm going to use this therapy. And we don't have that many therapies that have this level of evidence now.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [69]
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And regardless of whether it's primary prevention or secondary prevention. I guess, the guidelines have also tried to move away from some of these hard and fast benchmarks or numerically based thresholds. And perhaps, Dr. Bhatt, you could comment first on that, and maybe you, Dr. Budoff, on this sort of movement of the guideline to risk characterizations as opposed to primary prevention or secondary prevention around an arbitrary pivot?
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Deepak Bhatt, [70]
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Yes. Things are really changing the guidelines, as Dr. Budoff alluded to, in terms of risk stratification, even in terms of allocating statin therapy in the primary prevention world. Now we're saying, "Yes, you can use coronary calcium. It can be quite useful figure out who really does benefit from being in that group receiving statin therapy." So there's really an evolution in our thinking in terms of what those terms primary and secondary prevention mean. And I think the use of coronary calcium and to seek angiography in general is really poised to boom in this country. For a variety of different reasons, guideline related to non-guideline related. A lot of it's patient driven. Patients want to know, is there a trouble brewing in their coronary arteries. Is their plaque that's built up, and I think that will make these terms of primary and secondary prevention even more obsolete. The issue is, is a person at risk? That's the real issue. And you might define that by biomarkers, such as LDL elevation in terms of statin allocation, in terms of triglyceride elevation, in terms of consideration of icosapent ethyl. But on the other hand, you might move away from biomarker and say, "Oh, look, there's plaque in the left main, that's a problem regardless what the biomarker show."
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [71]
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Yes. I mean, I think, Matt, also and just in closing, before turning it back over to Elizabeth. I mean as both a clinical trial list, but really as a practicing physician, I think this, to me, is the science of medicine and the art of medicine, just like I think the EVAPORATE study is both the real hard-core science, but at the end of the day, it's about the outcomes, which is the quality of the science. Maybe you just want to comment a bit on that perspective with -- being a trial that's doing a lot of imaging. How do you sort of bring that into your discussion with patients in the context of primary prevention or secondary prevention?
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Matthew Budoff, [72]
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Yes. And I think it's really critical that people understand that whenever we put these buckets, the concept is primary prevention is lower risk and secondary prevention is higher risk. But what we're now seeing are high-risk primary prevention, which are really as high-risk as the other groups. So that's where I think we're starting to try to blur the lines as much as possible because as you said, it's one bad day. They had a heart attack, now they're secondary prevention. If they died of the heart attack, they never make it to secondary prevention, and we never treat them with these drugs that are only allocated to secondary prevention. It's too late to put the cholesterol pill under their tongue while we're doing CPR to try to get their cholesterol down. So we need better ways of identifying who's at risk of having a bad day in the near future. And we're going to turn to imaging. It's already happening. It's going to happen. I agree with Dr. Bhatt, I think it's going to happen faster, where we're going to want to take a look in our coronary arteries. And if they're all blocked up, we're going to be like, I'm high risk, I need to do things about it. And if we have tools that can help us either unblock the artery or lower our risk or do both, as I think we have evidence now with icosapent ethyl. I think that's going to be a therapy that doctors are going to turn to.
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Deepak Bhatt, [73]
--------------------------------------------------------------------------------
Yes, I agree. And even beyond just using imaging, there are still some simple clinical descriptors as if somebody has diabetes, essentially, that's an equivalent to someone that's had a prior heart attack, a number of observational and epidemiologic studies show that. So there are some things even without doing biomarkers or fancy imaging, you know that, that person is at risk.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [74]
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I think that's a great way to cap it because at the end, it really is about the individual interaction between the patient and the clinician about what's going to work best for them and work best in their life, no matter what the intervention is or not.
So I think with that, Elisabeth, did we cover many of the questions that you think are coming in?
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Elisabeth Schwartz, Amarin Corporation plc - Senior Director of IR [75]
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Yes, I think that was very helpful to put these results into context, and Craig, I want to thank you for leading this discussion today. Dr. Budoff, Dr. Bhatt, Dr. Weintraub, I'd like to thank you for being with us today, and I very much appreciate the contributions you're making to medical science.
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Craig B. Granowitz, Amarin Corporation plc - Chief Medical Officer & Senior VP [76]
--------------------------------------------------------------------------------
Thank you.
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Elisabeth Schwartz, Amarin Corporation plc - Senior Director of IR [77]
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Thank you.
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Operator [78]
--------------------------------------------------------------------------------
This concludes today's teleconference. You may now disconnect your lines at this time. Thank you for your participation, and have a wonderful day.


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[Magnetfeldfredy]

Korrupte Wallstreet, die uns Lemminge verarschen will, mich nicht mehr!

[flyingbeef]

Antwort auf Beitrag Nr.: 61.958.585 von bernie55 am 19.11.19 11:30:31

Ich glaube das ist Absicht, !

Der will Investoren die Botschaften "zwischen" den Zeilen finden können etwas sagen, nämlich jetzt das als no-buy einzustufen ist wie Geld aus dem Fenster werfen

Daher hat er das Kursziel nach oben angepasst bei gleichzeitiger "hey jetzt aber Vorsicht !" Meldung

Der denkt um 2 oder 3 Ecken der gute Mann uns ist ein schlauer Fuchs... naja oder auch nicht

[bernie55]

Antwort auf Beitrag Nr.: 61.958.477 von esaposse am 19.11.19 11:21:59

Zitat von esaposse: https://thefly.com/landingPageNews.php?id=2995848&headline=A…
😀
citi analyst hat vorher bei Pfizer gearbeitet
noch Fragen🙄🙄🙄

Dass diese Herabstufung von buy auf neutral absolut unsinnig ist, zeigt sich auch daran, dass das vorherige Kursziel von 23 USD gleichzeitig auf 27 USD erhöht wurde.

Quasi ein soft- downgrading.

[bernie55]

Antwort auf Beitrag Nr.: 61.954.658 von Cyberhexe am 18.11.19 21:57:36

Zitat von Cyberhexe:

Zitat von Magnetfeldfredy: Für mich sehr gute Ergebnisse, Evaporate zeigt den mechanism of action mit der Plaque Reduktion eindrucksvoll, und dass nach 9 Monaten noch nicht alles optimal ist beweisen auch die Reduce-It Studie, je länger man Vascepa nimmt desto besser werden die Ergebnisse!
Auch wurde das leidige Mineralöl-Placebo mit Evoporate beerdigt, super Interview, big pharma hat jetzt mit diesen Ergebnissen eindrucksvolle Beweise wie Vascepa wirkt und wird zur Übernahme führen:

Die Ergebnisse, die nur auf vorläufigen Daten basieren, zeigen, dass die Studie ihren primären Endpunkt, nämlich verringertes Plaquevolumen- (noch) nicht erreicht hat.

Bei den veröffentlichten Daten handelt es sich um einen neunmonatigen "Zwischenblick" auf eine kleine Studie mit 80 Patienten, die eigentlich für eine doppelt so lange Laufzeit ausgelegt ist.
Die Daten beinhalten auch Auswertungen auf andere Plaque-Wachstumsmaße, wobei die Plaque-Progressionsraten in der Mineralöl-Placebo-Gruppe identisch mit denen eines Placebos auf Cellulosebasis waren. Diese anderen Placebo-Daten stammen aus einer anderen Studie, sind jedoch genau auf die Daten der Placebo-Kohorte der neuen Vascepa-Studie abgestimmt.

"Bei vier verschiedenen Plaque-Markern, einschließlich der Gesamtplaque, wurde eine signifikante Verlangsamung der Progression festgestellt", sagte Matthew Budoff, UCLA-Professor an der School of Medicine.

Diese Verlangsamung von 42% im Vergleich zu Placebo war bei den bisherigen Wirksamkeitsdaten besonders bemerkenswert. Beruhigend ist vor allem "dass die verlangsamten Fortschrittsraten, die wir bei fünf der sechs von uns gemessenen Marker sahen, auf die Vorteile von Icosapent ethyl und nicht auf die Schäden von Mineralöl zurückzuführen sind", fügte er hinzu.

Superprima Zusammenfassung - THX

[esaposse]

Antwort auf Beitrag Nr.: 61.958.078 von bernie55 am 19.11.19 10:50:06

https://thefly.com/landingPageNews.php?id=2995848&headline=A…
😀
citi analyst hat vorher bei Pfizer gearbeitet
noch Fragen🙄🙄🙄

[bernie55]

Antwort auf Beitrag Nr.: 61.950.698 von Cyberhexe am 18.11.19 15:17:44

Zitat von Cyberhexe:

Zitat von bernie55: ...

ISTEINER CHURCHHILL..

Isteiner Churchhill - das ist nicht geflunkert, weil richtig übersetzt:

Hi cyberhexe,
hi cyberwitch

das hatte ich mir schon gedacht, dass es diesen Isteiner Kirchberg gibt. Ich fand die wortwörtliche Deutsch - Englisch - Kreativ - Übersetzung einfach nur zum Kringeln, du Spaßvogel.... you Jokebird

Grüße
bernie55

[bernie55]

..ohne Kommentar:

[bernie55]

Antwort auf Beitrag Nr.: 61.955.693 von Magnetfeldfredy am 19.11.19 06:49:01

Ohne Kommentar:

[Magnetfeldfredy]

Wir haben einen absoluten Gewinner mit Amarin, hier die Zusammenfassung der AHA2019 mit unglaublich guten Ergebnissen, dazu das historische 16:0 beim Adcom:

Amarin Highlights Key REDUCE-IT®-Related Data Presented at American Heart Association 2019 Scientific Sessions
[GlobeNewswire]
GlobeNewswire•November 18, 2019

REDUCE-IT USA results, in prespecified subgroup analyses, showed cardiovascular risk reductions across all endpoints, including 30% relative risk reduction in all-cause mortality

New analysis determined icosapent ethyl (Vascepa®) is highly cost-effective in patients from the REDUCE-IT study and, as is rarely found, may result in net healthcare cost-savings to patients, payers and society

Data showed prevalence of elevated risk of major cardiovascular events (mean 10-year ASCVD risk score greater than 20%) in more than 20% of patients on statins with triglycerides below 150 mg/dL

Interim EVAPORATE study provides important mechanistic data with relevance to the reduction in cardiovascular events seen in the REDUCE-IT clinical trial; final study results likely in early 2020

DUBLIN, Ireland and BRIDGEWATER, N.J., Nov. 18, 2019 (GLOBE NEWSWIRE) -- Amarin Corporation plc (AMRN), a pharmaceutical company focused on improving cardiovascular health, hosted a webcast today to discuss important data with study authors who presented at the American Heart Association 2019 Scientific Sessions, November 16-18. The data covered related to Vascepa® (icosapent ethyl) capsules, the landmark clinical outcomes study REDUCE-IT®[1] , as well as the cardiovascular risk of patients with elevated triglycerides, a type of fat in the blood.

“The more we study the REDUCE-IT data and the at-risk conditions of the patients studied in this important clinical trial, the better we understand the nature and extent of persistent cardiovascular risk among patients on statins and with elevated triglycerides, and how to address it,” said Craig Granowitz, M.D., Ph.D., chief medical officer, Amarin. “At Amarin, we are proud to have played a role in supporting and sharing data with the scientific and medical communities that could make a major difference in cardiovascular care, an area where the need for new and innovative treatment options is urgent and growing.”

About Cardiovascular Risk
The number of deaths in the United States attributed to cardiovascular disease continues to rise.2,[3] There are 605,000 new and 200,000 recurrent heart attacks per year (approximately 1 every 40 seconds), in the United States. Stroke rates are similar, accounting for 1 of every 19 U.S. deaths (approximately 1 every 40 seconds).4

Controlling bad cholesterol, also known as LDL-C, is one way to reduce a patient’s risk for cardiovascular events, such as heart attack, stroke or death. However, even with the achievement of target LDL-C levels, millions of patients still have significant and persistent risk of cardiovascular events, especially those patients with high triglycerides. Statin therapy has been shown to control LDL-C, thereby reducing the risk of cardiovascular events by 25-35% – but that still leaves 65-75% risk remaining.5 People with high triglycerides have 35% more cardiovascular events compared to people with normal (in range) triglycerides taking statins.6,[7],[8]

Key Data Presented at AHA and Reviewed During Amarin’s Webcast

“REDUCE-IT USA: Results from the 3,146 Patients Randomized in the United States,” – presented by Deepak L. Bhatt, M.D., M.P.H., Brigham and Women’s Hospital and Harvard Medical School.

Highlights: This prespecified REDUCE-IT subgroup analysis showed substantial risk reductions in the USA patients treated with icosapent ethyl 4 g/day versus placebo across all prespecified composite and individual primary and secondary endpoints, including 31% relative risk reduction and 6.5% absolute risk reduction in first occurrence of 5-point major adverse cardiovascular events (MACE), corresponding to a number needed to treat of 15 (NNT=15), and a significant 30% relative and 2.6% absolute risk reduction (NNT=39) in all-cause mortality in the USA subgroup.

Additional prespecified cardiovascular endpoints in which the REDUCE-IT USA subgroup showed significant relative risk reduction included myocardial infarction, cardiovascular death, and stroke, similar to the full cohort in the overall REDUCE-IT global results. These results were incremental to the cardiovascular risk reduction achieved by conventional therapy administered to the high-risk patients studied, including incremental to statin therapy.

The REDUCE-IT USA subgroup consisted of 3,146 patients (nearly 40%) of the previously reported full trial cohort. REDUCE-IT was not specifically powered to examine individual subgroups. P-values presented for the USA subgroup are nominal and exploratory with no adjustment for multiple comparisons. Differences in efficacy outcomes for the USA patients are best viewed as qualitative and not quantitative; nevertheless, the data are useful and provide reassurance that the results in the USA are at least as strong as the results seen outside the USA and in the trial overall.

The REDUCE-IT USA study results were also published in Circulation, AHA’s official scientific journal.9

“Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT,” – presented by William S. Weintraub, M.D., MedStar Washington Hospital.

Highlights: In this combined patient-level and simulation lifetime cost-effectiveness analysis, icosapent ethyl in high cardiovascular risk patients shows exceptional benefit with cardiovascular event reduction as well as cost-savings in-trial and over patients’ lifetime in many simulations. Findings of potential cost effectiveness of a medical therapy are rare. This analysis considered the current market cost for Vascepa and the potential savings from avoiding major adverse cardiovascular events, such as strokes and heart attacks, the cost of which can be high. This cost-effectiveness analysis was conducted by MedStar. As is typical, the cost-effectiveness analyses were not prespecified as part of the REDUCE-IT clinical trial design but did rely on the results of this landmark outcomes study.

“Many Statin Treated Persons with Borderline Triglyceride Levels are at Risk of ASCVD,” – presented by Nathan D. Wong, Ph.D., M.P.H, University of California, Irvine.

Highlights: This study showed prevalence of elevated risk of major cardiovascular events (a mean 10-year atherosclerotic cardiovascular disease (ASCVD) risk score greater than 20%) in more than 20% of patients on statins with triglycerides below 150 mg/dL. This suggests the need for greater lifestyle and other therapies to address remaining residual ASCVD risk.

“Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients with Elevated Triglycerides (200 – 499 mg/dL) on Statin Therapy (EVAPORATE) study,” – presented by Matthew J. Budoff, M.D., Los Angeles Biomedical Research.

Highlights: At the prespecified 9-month interim analysis, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% v. 43%, p=0.010), total plaque (non-calcified + calcified plaque) (p=0.0004), fibrous plaque (15% v. 26%, p=0.011) and calcified plaque (-1% v. 9%, p=0.001), after adjustment by baseline plaque, age, sex, diabetes status, baseline triglyceride levels, and statin use. However, there was no significant change in the primary endpoint of low attenuation plaque between active and placebo groups (74% vs 94%, p=0.469) at this 9-month interim look. This investigator-initiated study is continuing to its designed completion of an 18-month review.

EVAPORATE is the first study in the United States, which enrolled a total of 80 patients, to use multidetector computed tomography (MDCT) to evaluate the effects of icosapent ethyl as an adjunct to statin therapy on plaque characteristics in a high cardiovascular-risk population with persistent high triglyceride levels. Patients underwent interim scans at 9 months and are currently being followed for an additional 9 months with MDCT. Final results from this study are anticipated in early 2020.

Arterial plaque and coronary atherosclerosis are key factors leading to significant increases in the probability of acute obstructions and angina or other coronary artery disease signs and symptoms.

All of the analyses highlighted above were funded by Amarin.

A replay of the webcast will be available for two weeks following the webcast. To hear a replay of the webcast, dial 877-481-4010 (inside the United States) or 919-882-2331 (outside the United States). A replay of the webcast is also be available through the company's website, Amarincorp.com, in the Investor section. For both dial-in numbers please use conference ID 55923.

About Amarin
Amarin Corporation plc. is a rapidly growing, innovative pharmaceutical company focused on developing therapeutics to improve cardiovascular health. Amarin’s product development program leverages its extensive experience in polyunsaturated fatty acids and lipid science. Vascepa (icosapent ethyl) is Amarin's first FDA-approved drug and is available by prescription in the United States, Lebanon and the United Arab Emirates. Amarin’s commercial partners are pursuing additional regulatory approvals for Vascepa in Canada, China and the Middle East. For more information about Amarin, visit www.amarincorp.com.

About REDUCE-IT®
REDUCE-IT, an 8,179-patient cardiovascular outcomes study, was completed in 2018. REDUCE-IT was the first multinational cardiovascular outcomes study that evaluated the cardioprotective effect of icosapent ethyl, a unique prescription therapy, as an add-on to statins in patients with high cardiovascular risk. As defined in the published results of the study, the high cardiovascular risk patients, despite stable statin therapy, had elevated triglyceride levels (lower enrollment target of TG >135 mg/dL). As per the study’s design, approximately 71% of the enrolled patients had established cardiovascular disease and the other patients were diagnosed, as per trial enrollment requirements, as having diabetes and other cardiovascular risk factors.

More information on the REDUCE-IT study results can be found at www.amarincorp.com.

About Vascepa® (icosapent ethyl) Capsules
Vascepa (icosapent ethyl) capsules are a single-molecule prescription product which has been developed and studied for more than a decade and has been prescribed more than 8 million times in the United States. Vascepa, known in scientific literature as AMR101, has been designated a new chemical entity by the FDA. Amarin has been issued multiple patents in the United States and internationally based on the unique clinical profile of Vascepa, including the drug’s ability to lower triglyceride levels in relevant patient populations without raising LDL-cholesterol levels.

The FDA has not completed its review or made a final determination on a supplemental new drug application related to REDUCE-IT. FDA has not reviewed the information herein or determined whether to approve Vascepa for use to reduce the risk of major adverse cardiovascular events in the REDUCE-IT patient population.

Indication and Usage Based on Current FDA-Approved Label (not including REDUCE-IT results)

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 effect of Vascepa on the risk for pancreatitis and cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.

Important Safety Information for Vascepa Based on Current FDA-Approved Label (not including REDUCE-IT results) (Includes Data from Two 12-Week Studies (n=622) (MARINE and ANCHOR) of Patients with Triglycerides Values of 200 to 2000 mg/dL)

Vascepa is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to Vascepa or any of its components.
In patients with hepatic impairment, monitor ALT and AST levels periodically during therapy.
Use with caution in patients with known hypersensitivity to fish and/or shellfish.
The most common reported adverse reaction (incidence >2% and greater than placebo) was arthralgia (2.3% for Vascepa, 1.0% for placebo). There was no reported adverse reaction >3% and greater than placebo.
Adverse events and product complaints may be reported by calling 1-855-VASCEPA or the FDA at 1-800-FDA-1088. Patients receiving treatment with Vascepa and other drugs affecting coagulation (e.g., anti-platelet agents) should be monitored periodically.
Patients should be advised to swallow Vascepa capsules whole; not to break open, crush, dissolve, or chew Vascepa.

FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.

Important Safety Information for Vascepa based on REDUCE-IT, as previously reported in The New England Journal of Medicine publication of the primary results of the REDUCE-IT study:

Excluding the major adverse cardiovascular events (MACE) results described above, overall adverse event rates in REDUCE-IT were similar across the statin plus Vascepa and the statin plus placebo treatment groups.
There were no significant differences between treatments in the overall rate of treatment emergent adverse events or serious adverse events leading to withdrawal of study drug.
There was no serious adverse event (SAE) occurring at a frequency of >2% which occurred at a numerically higher rate in the statin plus Vascepa treatment group than in the statin plus placebo treatment group.
Adverse events (AEs) occurring in 5% or greater of patients and more frequently with Vascepa than placebo were:
peripheral edema (6.5% Vascepa patients versus 5.0% placebo patients), although there was no increase in the rate of heart failure in Vascepa patients
constipation (5.4% Vascepa patients versus 3.6% placebo patients), although mineral oil, as used as placebo, is known to lower constipation, and
atrial fibrillation (5.3% Vascepa patients versus 3.9% placebo patients), although there were reductions in rates of cardiac arrest, sudden death and myocardial infarctions observed in Vascepa patients
There were numerically more SAEs related to bleeding in the statin plus Vascepa treatment group although overall rates were low with no fatal bleeding observed in either group and no significant difference in adjudicated hemorrhagic stroke or serious central nervous system or gastrointestinal bleeding events between treatments.
In summary, Vascepa was well tolerated with a safety profile generally consistent with clinical experience associated with omega-3 fatty acids and current FDA-approved labeling of such products.

Important Cautionary Information About These Data
Further REDUCE-IT data assessment and data release are expected to yield additional useful information to inform greater understanding of the trial outcome. For example, detailed data assessment by regulatory authorities, such as the FDA and Health Canada, will continue and take time to complete and announce. The FDA advisory committee process and the final evaluation by regulatory authorities of the totality of efficacy and safety data from REDUCE-IT is anticipated to include some or all of the following, as well as other considerations: new information or analyses affecting the degree of treatment benefit on studied endpoints; study conduct and data robustness, quality, integrity and consistency; additional safety data considerations and risk/benefit considerations; and consideration of REDUCE-IT results in the context of other clinical studies. More detailed presentation of such considerations is set forth in the risk factors section of Amarin’s Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission. Because regulatory reviews are typically fluid and not definitive interactions between sponsor and agency on individual elements of an application and related information, Amarin does not plan to update investors further on ongoing communications with regulatory authorities. Amarin plans to announce the final outcome of such regulatory reviews when appropriate.

Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the use of Vascepa to potentially help millions of patients. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include the following: uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals; the risk that data interpretations or other information from third parties, the regulatory review process, regulatory authorities and in connection with an advisory committee could be made public that are negative or may delay approval or limit Vascepa’s marketability; the risk that special protocol assessment (SPA) agreements with the FDA are not a guarantee that FDA will approve a product candidate; the risk associated with the FDA's rescinding the REDUCE-IT SPA agreement; the risk related to FDA advisory committee meetings; and the risk that the FDA may not complete its review of the REDUCE-IT sNDA within the timing expected. A further list and description of these risks, uncertainties and other risks associated with an investment in Amarin can be found in Amarin's filings with the U.S. Securities and Exchange Commission, including its most recent Quarterly Report on Form 10-Q. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Amarin undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Availability of Other Information About Amarin
Investors and others should note that Amarin communicates with its investors and the public using the company website (www.amarincorp.com), the investor relations website (investor.amarincorp.com), including but not limited to investor presentations and investor FAQs, Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Amarin posts on these channels and websites could be deemed to be material information. As a result, Amarin encourages investors, the media, and others interested in Amarin to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Amarin’s investor relations website and may include social media channels. The contents of Amarin’s website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Amarin Contact Information

Investor Inquiries:
Elisabeth Schwartz
Investor Relations
Amarin Corporation plc
In U.S.: [phone]
[e-mail]

Lee M. Stern
Solebury Trout
In U.S.: [phone]
[e-mail]

Media Inquiries:
Gwen Fisher
Corporate Communications
Amarin Corporation plc
In U.S.: [phone]
[e-mail]

References

1 Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019;380:11-22.

2 American Heart Association. Heart Disease and Stroke Statistics – 2019 Update: A Report from the American Heart Association. Published January 31, 2019.

3 American Heart Association / American Stroke Association. 2017. Cardiovascular disease: A costly burden for America projections through 2035.

4 American Heart Association: Heart Disease and Stroke Statistics -- 2019 At-a-Glance.

5 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.

6 Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.

7 Toth PP, Granowitz C, Hull M, et al. High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: A real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk. J Am Heart Assoc. 2018;7(15):e008740.

8 Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.

9 Bhatt DL, Miller M, Brinton EA, et al. REDUCE-IT USA: Results from the 3,146 Patients Randomized in the United States. Circulation 2019. DOI: 10.1161/CIRCULATIONAHA.119.044440.


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