Amarin Corporation plc (AMRN) Q3 2019 Earnings Report, Transcript and Summary

Welcome to Amarin Corporation’s Conference Call to discuss its financial and operating results for the Third Quarter of 2019. [Operator Instructions] I would like to turn the conference call over to Elisabeth Schwartz, Senior Director of Investor Relations of Amarin.

Good morning. 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 are current expectations regarding our commercial and financial performance, including levels of Vascepa shipments and prescription, Vascepa’s product and licensing revenues, costs and other commercial metrics, gross margin expenditures and the adequacy of our financial resources, our current expectations regarding regulatory reviews, including our expectations related to the upcoming advisory committee meeting regarding our REDUCE-IT sNDA and our expectations for Vascepa label expansion, our current expectations for scientific presentations, publication and related timing thereof, our expectations that REDUCE-IT results could lead to a new treatment paradigm and the patient population studied, our plans and preparation for expanded promotion of Vascepa and related marketing positioning and potential, our plans to purchase additional supply of Vascepa, our goals regarding the timing and scope of international expansion and our current plans for sales force and other commercial expansion. These statements are based on information available to us today, November 5th 2019. We may not actually achieve our goals, carry out our plans or intentions or meet the expectations disclosed in our forward-looking statements. Actual results or events could differ materially. So you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change. Our Forward-looking statements do not reflect the potential impact of significant transactions when they enter into such as mergers, acquisitions, dispositions, joint ventures or any material agreements that we may enter into, amend or terminate. For additional information concerning the factors that could cause actual results to differ materially, please see the Forward-looking Statements section in today’s press release and the Risk Factors section of our quarterly reports on Form 10-Q for the quarter ended September 30th 2019. These documents have been filed with the SEC and are available through the Investor Relations section of our website at amarincorp.com. We encourage everyone to read these documents. This call is intended for investors and Amarin is not intended to promote the use of Vascepa outside its approved indication. Please note that we are also providing slides to accompany this morning’s call. These slides, which can be found on our website at amarincorp.com in the Investor Relations section under the sub-category Events and Presentation, summarize some of the key update discussed on today’s call. Finally, an archive of this call will be posted on the Amarin website also in the Investor Relations section. I will now turn the call over to John Thero, President and Chief Executive Officer of Amarin.

Good morning. Thank you for listening to our comments today regarding Amarin’s third quarter progress in this busy and exciting time. Amarin’s growth was again positive in Q3. We reported record revenue levels, positive cash flow and a strong financial position, while adding to the breadth, depth and experience of our commercial organization. We will comment further on such operating matters during this call. First, I will address our pending sNDA with the U.S. Food and Drug Administration in which we are seeking a cardiovascular risk reduction indication for Vascepa based upon the landmark results of the REDUCE-IT cardiovascular outcome study. The targeted PDUFA date for FDA action on this sNDA is December 28th of this year. As part of its review, the FDA is planning an Advisory Committee meeting or ADCOM to be held on November 14th. We are looking forward to the ADCOM with cautious optimism. The ADCOM should be an opportunity to provide education and insights regarding the differentiated effects of Vascepa, the positive results of REDUCE-IT and the potential to use Vascepa and it’s cardio protective results to help millions of patients. Based upon REDUCE-IT results, if all statin-treated patients in the United States with elevated triglyceride levels were treated with Vascepa, we estimate that major adverse cardiovascular events such as stroke, heart attack and cardiovascular death could in aggregate be reduced by 150,000 to 450,000 per year. We believe that this represent a tremendous potential healthcare improvement, not just for at-risk patients, but also for their families and society. Fewer major adverse cardiovascular events potentially translates into increased productivity and lower healthcare spending for these expensive events and subsequent patient rehabilitation. As we have expressed previously, it is common for the FDA to have ADCOMs in conjunction with first-in-class drug applications such as our sNDA for Vascepa. At the ADCOM, we expect questions on a range of topics including questions regarding REDUCE-IT trial design, and about the demonstrated efficacy and safety of Vascepa. Some of these questions may pertain to potential labeling language. As is typical of ADCOMs, we expect that some of these questions will be intentionally tough. We are a science-driven company, and we believe that we are ready for such potential questions. Based upon our current understanding of FDA’s focus and perspectives, we expect the EMDAC meeting to cover the following topics. Among others, related to our REDUCE-IT sNDA. These topics are consistent with topics typically explored at FDA advisory committee meetings and cover matters consistent with Amarin’s prior disclosures and available data. Review of patient population studied in REDUCE-IT and how best to communicate this population to prescribers and other healthcare professionals, including considerations related to LDL-cholesterol management on statin therapy, triglyceride levels as an identifier cardiovascular risk and other identifiers of high cardiovascular risk. Analysis of the degree of treatment benefit in the overall study population for the primary endpoint of the study, as well as in different REDUCE-IT subgroups. For example, as previously disclosed, we established cardiovascular disease secondary prevention cohort, which consistent with the trial design, represented approximately 70% of enrolled patients in REDUCE-IT and had a high observed event rate experiencing a numerically higher effect size, 27% relative risk reduction, then the high-risk diabetic primary prevention cohort, which consistent with the trial design, represented approximately 30% of the enrolled patients and had a relatively lower observed event rate and experience of 12% relative risk reduction in exploratory analysis of the smaller subgroup. Analysis of the degree of treatment benefit on specific studied endpoints in the different subgroups. For example, as previously disclosed, beyond the primary endpoint and key secondary endpoint, seven secondary endpoints of different clinical relevance were achieved to varying degrees of impact and degrees of statistical significance in the order of sequential statistical testing within the pre-specified hierarchy, including myocardial infarction, cardiovascular death and stroke. Analysis related to study conduct and data robustness, quality, integrity and consistency. For example, as previously disclosed, REDUCE-IT was a single clinical trial conducted based upon a special protocol assessment agreement with the FDA and as is typical of all cardiovascular outcome studies, related analysis are expected on the overall strength and limitations of the study data to support the indication sought as described above, considering factors, including but not limited to, the use of mineral oil used in the study and questions explored in past FDA reviews and raised publicly since then over the possibility of an interaction of the placebo which done that some have argued could have led to reduced absorption of statin medications. We do not believe such an interaction occurred for reasons previously disclosed among others. Consistent with the publication of REDUCE-IT results in the New England Journal of Medicine, We believe FDA has assessed that even if placebo based upon indirect evidence of potential effect, that exploratory analysis indicates the effect, if any of mineral oil on bio-marker values, such as LDL-cholesterol values on the time to the primary endpoint is numerically small and unlikely to change the overall conclusion of treatment benefit. We also expect analysis on safety data and related risk benefit considerations in light of the above. For example, as previously disclosed, overall safety findings in REDUCE-IT were generally consistent with product labeling in available data on the omega-3 class. More patients in the Vascepa group experienced an adjudicated event of atrial fibrillation or atrial flutter requiring hospitalization 24 hours or greater compared with patients in the placebo group, 3.1% versus 2.1%. And more patients experience any treatment-emergent adverse event of atrial fibrillation or atrial flutter in the placebo arm versus placebo. The incidence of fibrillation and atrial flutter was greater in the subset of patients with the previous history of atrial fibrillation or flutter and the relative imbalance was numerically greater between arms in the subgroup compared with the imbalance in those patients without a previous history. Additionally, more patients in the placebo group experienced an adverse event of bleeding, compared with patients in the placebo group. Excluding hemorrhagic stroke, which was an adjudicated efficacy event, 482 patients, 11.8%, in the Vascepa treatment arm experience bleeding events, compared to 404 patients, 9.9% in the placebo treatment arm, in each case consistent with prior disclosures. Such discussion is likely to include consideration of disclosure of safety information to prescribers and patients. And also to consider the downstream effects typically associated with these adverse events, which in the case of atrial fibrillation, in atrial flutter, were generally lower on the Vascepa arm than the placebo arm with consideration of relative benefit risk. We cannot be sure that the same content or more or less will be presented or discussed as key topics at the EMDAC meeting. In preparing for the FDA’s ADCOM, we have held a series of market comps in which we invited leading physicians and statisticians to challenge us and our advisors with questions which the invited professionals believe could or should be asked at the actual ADCOM. We believe we are ready for a successful ADCOM. Regarding potential labeling of Vascepa, some panelists at the mock ADCOMs have suggested that the language of label should be relatively broad reflecting that educated healthcare professionals know their patients best and don’t need a label to be unnecessarily prescriptive or restrictive. Other panelists have expressed a preference for having more detail in a label. Some of this discussion has involved, for example, the degree to which reference to patient characteristics, patient age, cholesterol levels and triglyceride levels should be in the label. And for the primary prevention patients, some of the discussion has involved the degree to which patients need to have diabetes and to what other risk factors should be considered when selecting patients who might benefit from use of the drug. While opinions have varied regarding the levels of such detail the overall perspective of these mock ADCOMs has been that there is a meaningful cardiovascular risk reduction indication, which is applicable for Vascepa. Again, we cannot be assured that the ADCOM on November 14th will parallel while we have heard at the mock ADCOMs regarding questions, feedback or general support for Vascepa label expansion. And as is typical, we don’t yet know the identities of the panelists whom the FDA has selected for the ADCOM. The team leading the presentation for Amarin will include the study’s principal investigator, Dr. Deepak Bhatt. In preparations for ADCOMs, there are briefing books prepared, first by the drug sponsor, in this case, Amarin; and then by the FDA. After these briefing books are drafted, they go through a quality review process at the FDA, which includes, among other matters, reduction of any patient specific information following this quality review process, an appropriate redaction of personal information, the FDA makes the briefing books public. It is up to the FDA, and not Amarin, to make the briefing books public. Making the briefing books public typically occurs two days before the commencement of the ADCOM. We expect this process to be no different for the upcoming ADCOM for Vascepa. As is typical, panelists at the ADCOM will be supplied the briefing books and they may ask their own questions regardless of whether such questions are covered in the briefing books or not. In addition to briefing books both the sponsor and the FDA will prepare slides to present to the invited panelists at the ADCOM. As is typical, Amarin will not see the FDA slides prior to their presentation at the ADCOM. In our mock ADCOMs, we have attempted to prepare for a range of potential questions beyond those which we most anticipate will be asked. Recall that the REDUCE-IT study was designed under a Special Protocol Assessment agreement with the FDA. Further before this important study was completed and unblinded, Amarin reached agreement with the FDA regarding the details of the statistical analysis plan and the definitions of the clinical endpoints. These factors combined with Amarin having collected final vital data, a 99.8% of the patients studied should, we believe, help mitigate some of the types of concerns often heard at ADCOMs pertaining to quality of data or differing views on methods of data analysis. While it is possible that FDA may ask Amarin additional questions in conjunction with its review of Amarin’s sNDA. We have thus far responded to all of the FDA’s questions and data requests. As you know, it would not be constructive to our interactions with the FDA for us to disclose the details of all such interactions. And during this review all Amarin personnel with knowledge of such interactions have been in a closed window period regarding public trading in shares of Amarin. And of course, we have taken extensive steps to safeguard sensitive information. The outpouring of support Amarin has received from healthcare professionals, patients, investors and other stakeholders has been overwhelming and gratifying. Approximately 100 comments have been written to FDA expressing their reasons for why Vascepa should be approved promptly for cardiovascular risk reduction. And many doctors and patient advocacy groups have volunteered to help Amarin with the ADCOM. Reading these letters, many of which reflect personal experiences, is inspiring. If you’re interested in reading them, they are publicly available at bit.ly/36ypKev. As you know, various Medical societies have already, in advance of FDA approval, change their treatment guidelines or otherwise provided notice recognizing the cardioprotective effects of of icosapent ethyl, the brand name, which is Vascepa. Beyond statin treatment in patients with triglyceride levels of 135 mgs per deciliter or greater. These are leading organizations in Cardiology, endocrinology and lipidology, including ADA, ESC, EAS, AHA and NLA. It is notably inspiring to see ESC, which is the European Society of Cardiology and EAS, which is the European Atherosclerosis Society recognize the value of Vascepa in their guidelines as Vascepa is not yet available in Europe. And we appreciate getting the support of NLA, the National Lipid Association as the multi-factorial effects of Vascepa extend beyond lipid management. Each of these Medical societies recognizes the significant cardiovascular risk, which exist beyond current standards of care for cardiovascular risk management, including cholesterol management. Because the ADCOM will be conducted during the trading day on November 14th, for reasons which I hope are obvious, we intend to ask NASDAQ to halt trading in Amarin shares until the ADCOM is complete and its results are communicated by us. Please do not read anything positive or negative into such trading halt other than our desire to ensure a level playing field. The FDA makes a live broadcast of its ADCOM available. In addition to pursuing U.S. regulatory approval of Vascepa for cardiovascular risk reduction, our international initiatives remain on track. For Europe we plan before the end of this year to submit an application seeking approval of Vascepa for the first therapy in Europe to address the substantial residual cardiovascular risk that persists beyond cholesterol management as studied in REDUCE-IT. In Canada, it is our understanding that Health Canada is progressing on its review. In the Middle East, we continue to anticipate further approvals of Vascepa. In China, in the clinical study of Vascepa being conducted by our partner, the pace of patient enrollment has been increasing positioning that biomarker focused study for potential completion in 2020. Coincidentally, starting on the weekend following the ADCOM for Vascepa, the American Heart Association or AHA is holding its Annual Scientific Sessions. At that meeting, which this year will be in Philadelphia, there were seven known presentations, which pertain to Vascepa. We are pleased to support these scientific presentations. We believe that these presentations include valuable insights. However, in our view, none of the data being presented is needed for the review of the sNDA we have submitted to the FDA. Because not everyone can attend AHA, at the end of their program, Amarin intends to conduct a webcast in which leading physicians will summarize information presented at the AHA Conference, which they believe are potentially applicable to Vascepa in the patient population we seek to address. I now hand the discussion over to Mike Kalb, our CFO, to cover Amarin’s recent financial results. When he is done, I will add a few comments for further perspective, and then with the time remaining, we will respond to some questions. Mike?

Thanks, John. As mentioned at the start of this call, both our Form 10-Q and our press release issued today discussing Amarin’s Q3 results can be found on Amarin’s website. They include details which go beyond the highlights we will cover in this morning’s call. Our third quarter total revenue was $112.4 million. This was a record high for Amarin and an increase of 103% over the same period in 2018. We recorded total revenue of $286.5 million for the nine months ended September 30, 2019. This also was a record high for Amarin and an increase of 89% over the same period in 2018. This nine-month revenue also well exceeds the 12-month total for 2018. As expected, nearly all of our total revenue consisted of product revenue from Vascepa sales in the United States. The increase in net product revenue was nearly all attributable to increases in new and recurring prescriptions of Vascepa. Such prescription levels reached record highs for Vascepa during the reported three and nine-month periods of 2019. The net selling price of Vascepa varies modestly from quarter-to-quarter and was slightly higher in Q3, 2019 than the same quarter of 2018, but remained relatively unchanged for the nine months ended September 30, 2019, as compared to the same period in 2018. The estimated number of normalized total Vascepa prescriptions based on data from Symphony Health and IQVIA, for the three months ended September 30, 2019 were approximately 865,000 and 787,000 respectively compared to 458,000 and 417,000 respectively in the three months ended September 30, 2018. These estimates reflect increases of 89% in the third quarter of 2019 over the same period of 2018. As a reminder, Amarin recognizes product revenue based on sales to regional wholesalers and specialty pharmacy providers in the United States or collectively its distributors or its customers and not based on prescription levels estimated by Symphony Health or IQVIA. We referenced the data from Symphony Health and IQVIA in response to request for such information from investors. Channel inventory, meaning the amount of Vascepa held at independent distributors varies from quarter-to-quarter based on the ordinary course of business. At the end of September, it was estimated to be within the normal business range of approximately two to three weeks of Vascepa supply on hand at distributors. Such channel inventory is separate from inventory held by Amarin. In addition to net product revenue licensing revenue recognized by the Company were $1.1 million and $600,000 in the nine months ended September 30, 2019 and 2018 respectively, related to the amortization of milestone payments and other factors impacting revenue recognition for licensing fees under agreements for the commercialization of Vascepa outside the United States. Amarin guidance for 2019 total revenue remains unchanged. For 2019, we anticipate reaching between $380 million and $420 million in total revenue. We do not intend to provide quantified guidance for 2020 until Vascepa’s label is known and our launch of Vascepa for cardiovascular risk reduction has commenced. John will In a moment to discuss our preparations for that launch. Our gross margin on product sales for the nine months ended September 30, 2019 was 77%, up from 76% in the same period of 2018. Our spending levels have also increased, but the growth rates, which are considerably slower than our revenue growth. Selling, general and administrative or SG&A expense for the nine months ended September 30, 2019 were $227.6 million, an increase of 55% over the same nine-month period in 2018. This increase is due primarily to increased commercial and other promotional spend for expansion following successful REDUCE-IT results, which were announced on September 24, 2018, including cost for expanding of the Amarin sales team to – sales representatives at the beginning of 2019 and some recent further expansion to support the assumed launch of Vascepa for a cardiovascular risk reduction indication after the December 28, 2019 PDUFA date. We anticipate that SG&A spending will increase further as we further prepare for and then assuming FDA approval, launch Vascepa for the cardiovascular risk reduction indication currently under review by the FDA. Research and development or R&D expense for the nine months ended September 30, 2019 was $23.3 million, a decrease of 47% compared to the same period in 2018. This decrease is primarily due to timing of completion of the REDUCE-IT cardiovascular outcome study and related costs. Under U.S. GAAP, Amarin reported a net loss of $3.5 million in the third quarter of 2019 or basic and diluted loss per share of $0.01. This net loss included $8 million in non-cash stock-based compensation expense. Amarin reported a net loss of $24.5 million in the third quarter of 2018 or basic and diluted loss per share of $0.08. This net loss included $6.7 million in non-cash stock-based compensation expense. Excluding non-cash gains or losses for stock-based compensation, non-GAAP adjusted net income was $4.5 million for the third quarter of 2019 or non-GAAP adjusted basic and diluted earnings per share of $0.01, compared to non-GAAP adjusted net loss of $17.8 million for the third quarter of 2018 or non-GAAP adjusted adjusted basic and diluted loss per share of $0.06. As of September 30, 2019, we had cash and cash equivalents and restricted cash of $677.1 million, an increase of $426.4 million from December 31, 2018. As of September 30, 2019 we also had accounts receivable net of $103.6 million, all of which was current and the inventory of $54.6 million. The increase in our reported cash at September 30, 2019 includes both the results of our previously announced equity financing and cash flow positive operations for the quarter. Based on our current plans, we believe that our cash resources are sufficient to support the requirements for a successful launch of Vascepa without the need for additional funding. For the three months ended September 30, 2019, excluding cash inflow from financing, Amarin was cash flow positive reflecting growing revenue levels, expense management and the timing of inventory purchases. For the nine-month period ended September 30, 2019, further excluding cash flow associated with all forms of financing and R&D payments, most of which relate to the REDUCE-IT study and associated regulatory affairs activities, and excluding payments made in preparation for expansion upon positive REDUCE-IT results such as increasing Vascepa inventory levels. The Company was $27.6 million net cash flow positive. Amarin anticipates increasing its cash outflows in the fourth quarter of 2019 and in 2020 to prepare for and launch Vascepa in the U.S. for the cardiovascular risk reduction indication we are seeking. Such added cash outflows will, in addition to expanding Amarin’s sales force size and promotional initiatives, also include spending for further medical education and investment in the growth of Vascepa inventory levels. At the start of 2019, Amarin projected that it could spend $50 million to $75 million more in 2019 for building inventory levels and testing the capacity of our suppliers, then would be needed to support our then current revenue forecast. While some of these increased purchases have been used to support higher then initially guided revenue levels, some of these incremental orders for inventory growth are anticipated to be delivered in late 2019 for payment either late this year or early next year such that cash flow from operations may be negative in Q4, 2019 despite anticipated higher revenue levels. As of September 30, 2019, Amarin had approximately 357.2 million American Depository Shares or ADSs, and ordinary shares outstanding, 28.9 million common share equivalents of Series A Convertible Preferred Shares outstanding and approximately 16.3 million equivalent shares underlying stock options at a weighted average exercise price of $6.21, as well as 9.4 million equivalent shares underlying restricted or deferred stock units. I will now turn the call back over to John for closing remarks. John?

Thank you, Mike. We are planning for success regarding an expanded label for Vascepa. As previously expressed, we intend to increase the size of Amarin’s U.S. sales force from 400 to 800 sales representatives for the launch of Vascepa for cardiovascular risk reduction assuming FDA approval. In Q3 2019, we hired or internally promoted nearly all of the sales management team needed to support this growth. Included in this expansion is the addition of Joe Balzer as Senior Vice President of National Sales. Joe is very experienced with a track record of success in leading teams, which are much larger than what we are growing to initially. He has surrounded himself with good people, including retention of the sales leadership team responsible for getting us to this stage and who will now manage sales for significant portions of the U.S. under Joe’s overall responsibility. In Q3, we continued to witness increased prescription rates from physicians called on by our veteran Vascepa sales representatives, and by our newest sales representatives. The sales representatives we added near the beginning of this year continued to contribute faster than we initially anticipated. Their progress adds to our confidence as we move to hire and train additional waves of new sales representatives. In recent months, we received over 10,000 job applications for the sales positions we are seeking to hire. We recently added some of these incremental sales representatives. Many of our recent hires are referrals from our existing sales representatives. We are confident that we will be able to recruit and train qualified people to support our planned expansion for launch of Vascepa in early 2020 based upon the cardiovascular risk indication we are seeking in assumed approval of Vascepa on or before the December 28 PDUFA date. Other preparations for this launch beyond sales force expansion are also progressing, including managed care outreach and education. While managed care has generally viewed Vascepa to be reasonably priced, recently presented third-party analysis showing that Vascepa is cost-effective, will aid our activities to ensure that Vascepa is available and reimbursed when prescribed to help at-risk patients. We look forward to potentially more comprehensive analysis regarding the cost effectiveness of Vascepa to be presented later this month at the Scientific Sessions of AHA. Before beginning the Q&A portion of this call, I will also touch upon the summary judgment ruling issued by the court hearing our ANDA litigation in Nevada on October 29th. The litigation is proceeding toward the previously announced trial date of January 18th. If this litigation goes to trial, it will be a trial held by a Judge, not a jury trial. We are quite pleased with the court’s summary judgment ruling. Seeking summary judgment at this stage in ANDA patent litigation is a common approach for generics to seek an early end to litigation and for both parties to seek to limit the scope of issues at trial. The Judge ruled against the ANDA filer’s summary judgment motion that sought to end the case at this early stage in their favor, enrolled more in Amarin’s favor to limit the scope of issues that remain for trial. We see this ruling as strengthening our position in the litigation by eliminating from the case several potential lines of generic argument. As such, the ruling strengthens Amarin’s position should it be determined that case settlement is in the Company’s best interest. We look forward to litigation progressing. Due to the complex nature of patent litigation, we refer investors to the court’s order and other court documents for further detail, which can be located through the FAQ section of our Investor Relations website. We also refer investors to the Risk Factors section in today’s Form 10-Q for detail. We intend to continue to vigorously defend our patents, but don’t intend to go into more detail on that today. With that, we conclude our prepared comments and we’d like to open the line to some questions. Operator?

[Operator Instructions] Thank you. The first question today comes from the line of Yasmeen Rahimi with Roth Capital Partners. Please proceed with your question.

Hi, team. Thank you, John, for your thoughtful prepared remarks in regard to ADCOM procedure and topics. You mentioned in your prepared remarks that some of the questions might be tough versus others. I would love to hear your thoughts on which of the topics we could consider more tough? And then the second question is in regards to EVAPORATE. We’re excited to look at the data at AHA, maybe you can tell us what percentage progression like you expect to see and what is the purpose of this study? Is it just helping us mechanistically support Vascepa or do you plan to utilize the data into the label? And thank you again for taking my question.

Yasmeen, thanks for the questions. Good morning. With respect to ADCOM questions, the nature of an ADCOM really is to bring in advisors to the FDA. These are smart people and they all want to be heard. So there is a sort of natural adversarial tone that goes into those questions. And you can see that count for other products that people opt to ask tough questions at the end. They may have more different views and questions that they ask, but they ask pointed questions, try to get to answers on topics. I think we have good responses and in fact, very good responses to what we think will be the likely question at the meeting, but I – my purpose of mentioning that they’re likely to be tough questions is to, in some respect state the obvious, and to – for those who are potentially attending or listening to the ADCOM not to take out of context difficult question. That’s the nature and purpose of an ADCOM is to be challenge on the data. And we think we’ve been challenged on the data in various medical conferences. We think we’ve been challenged on data and reviews by publications like the New England Journal of Medicine, Journal of American College of Cardiology. And I believe and I think we’ve seen that deeper people dig into the data the stronger the data gets. So tough questions and reference to tough questions is really as a contextual piece, but there is nothing that we’re walking into that ADCOM fearing as being a real got that we’re not prepared to answer. With respect to EVAPORATE, as an investigator initiative study, the mechanism of action of Vascepa is multi-factorial. As you may recall, it was study done in Japan, called the Cherry Study. In the Cherry Study, use – because I don’t know what acid on top of statins, compared to statin alone. And in that study, which was a decent size not huge, but 200-patient study. It showed that the use of EPA, Eicosapentaenoic acid does on top of statin or statin alone essentially doubled the prevalence of flat regression versus not having the EPA, added techniques for assessing, plaque have continued to improve, they’re not perfect, but they’ve continued to improve. We’ve got a number of investigators who are very interested in looking at plaque and trying to better understand plaque progression that may be occurring with EPA. And so we’re looking forward to the all seven presentations at AHA including the one relative to EVAPORATE. That being said, the sNDA has been submitted, the sNDA include all the data, we believe, is necessary to support the approval of our drug and as is the case for many breakthrough therapies, I’m sure that the data that we have generated with Vascepa will generate in current research and lots of different areas going forward as people try to dissect and further understand different mechanisms, that type of scientific research is terrific, but we don’t believe that EVAPORATE results as interesting as they may be are necessary for the approval of the drug.

Thank you, team, and best of luck next week, not that you need it.

The next question is coming from the line of Michael Yee with Jefferies. Please proceed with your question.

Hey, John. Congrats on the good quarter and progress so far. Two questions for you. One was related to the commentary around the ADCOM and how you think about a label? It does seem that a lot of the discussion questions you mentioned are perhaps around labeling and population. So could you just level set our expectations as to the – what you expect for what a broad population or broad label is? Is that something like PCSK9 or would you expect that its possible commentary is around primary and secondary prevention or even trig levels? And then as it relates to the second question, can I confirm that you did get a preview briefing document at advance already that you’ve gone through that and that the comments you made are many of the topics that are in that briefing document, including your comments around mineral oil? Thanks so much.

Michael, good morning, thanks for the questions. With regard to documentation that we’ve seen, we’ve had numerous questions from the agency. As you might expect in the FDA review over those multiple months since it was submitted in March. We’ve had various other forms of communication as briefing books at this point in time or not final and we’ve got a pretty good sense of what might be in it from a draft perspective, but they’re not final. And I wouldn’t want to put us a stronger period after something that’s not a final document at this stage. With regard to the ADCOM and questions, I do think that there are likely to be a number of questions, which could be interpreted as questions that would pertain to labeling. That being said, that doesn’t mean that those will be the only questions. And as it pertains to labeling on from a macro perspective, what we’ve studied where statin treated patients with elevated triglycerides and other cardiovascular risk factors. How that is best described to physicians and patients, there are varying opinions on and those varying opinions get into, does it make sense to quantify LDL, does it makes sense to quantify triglyceride levels. So does it make sense in the label to get into definitions or salvage cardiovascular disease and diabetes and other risk factors. And does age matter, there is a – we have a long list of entry criteria that’s used for a clinical outcome study and use those in outcome study to ensure a consistent results across whole forms of study. And then this is not a unique topic, if you get into this, disrupt FDA considerations as to how is that information from an outcome study best communicated to physicians and patients. And there are always varying views on that some – both would prefer to have it – be really left to the judgment of physicians and knowing that physicians understand that patients the best. And if you describe patients being at risk. Docs will know that is, and others think that maybe an indication ought to be more detail than that. We have not entered into labeling is for voice do we not we’ve not entered into labeling discussions with the FDA. It is typical to not enter into those labeling discussions and after – till after ADCOM is complete. But it’s somewhat inescapable during at ADCOM or views not to be shared on topics that could inform FDA’s thinking relative to labeling considerations, whether the FDA chooses to follow those advice of the Committee are not in those matters. So it is – always remains to be seen.

Got it. Thanks.

Our next question comes from the line of Ami Fadia with SVB Leerink. Please proceed with your question.

Hi. Good morning. Congrats on the nice quarter. I had two questions regarding some of the topics you mentioned, John with regards to what might come up at the ADCOM. Firstly, with regards to the patient population, can you talk to the minimum TG level of patients that were enrolled in the REDUCE-IT study? I believe that the SPA was for 200 TG level, but you enrolled patients all the way from 135. Can you talk to sort of some of the considerations that may be involved in thinking about what patients Vascepa would be prescribed for from a labeling perspective? And also what percent of patients in the trial were in that 135 to 200 range? And then separately regarding the interaction between mineral oil and statin, you’ve sort of expressed some of your views on the Company website. But I also wanted to understand, do you believe that it is possible to do some sort of a drug-drug interaction study between mineral oil and statins? And then do you think it would be informative in clarifying that interaction and what type of time and resources may be required to do something like that? Thank you.

Thanks, Ami, for the questions. With respect to the patients' population, the study was designed to use triglycerides as an identifier risk and then now this gets a little bit tricky. And I think you know that this further benefit of other is – we were not trying to demonstrate that lowering triglycerides alone provides all the benefit from the study. So we’ve got triglycerides, which I think are really pretty well established as a marker of risk, but as a modifiable risk factor, still known in the Vascepa has multi-factorial effects with one is triglyceride lowering. When we went into the study REDUCE-IT, we went into the study with a statistical plan and analysis that assumed a lots of different things. We assumed that obviously all the patients are going on statins, all patients in elevated triglycerides. We assume things like 70% or more going to be secondary preventions. 30% are going to be primary prevention. We also had assumptions in our modeling for the sort of number of patients or the balance of patients who might have triglycerides at different levels, so that we would try to get a spectrum of data based upon different triglyceride levels. When we began the study, the threshold was triglycerides 150 above with a 10% allowance of the lower boundary, was effectively 135. When you enroll patients in this study, there is a mark-up that people have at the beginning of the study when they get enrolled, then they go through a wash-out and randomization period and then there is another marker at the measure of their triglycerides at the end of that. And where they’re actually beginning to receive Vascepa therapy or placebo, and during that phase, some patients had triglycerides went up and some down like that we had some patients who got treated at the beginning of the study in around below 80s in terms of triglyceride levels. During the conduct of the study, we found that early on, in sort of at midway enrollment, we found that a greater proportion of the patients enrolled in the study than what we had been targeting your high triglyceride levels below 200 mg per deciliter, such that as we looked at our enrollment we sort of got to the stratification that we wanted to patients with trig low 200, fairly early on and it didn’t have enough patients in our view, against what we had originally forecast of patients with trigs above 200 and that point in time we switched to enrolling only patients with trig above 200, but of course, continuing to treat and monitor those patients with trigs below 200. At the end, it probably didn’t really matter, because the results were consistent across the triglyceride levels. And there’s been some data out there, which shows cardiovascular risk as it relates to triglyceride levels, which shows that your cardiovascular risk really begins to increase with trig levels are within a 70 mg to 80 mg per deciliter range and then goes up. And doesn’t go down, but sort of plateaus between the 150 mg and 200 mg per deciliter range. So essentially all the patients, whether it’s 135 and above, or 150 above or 200 above all had elevated triglycerides and elevated cardiovascular risk based upon this other data that we’re referring to. The elevation of risk isn’t all two different for patients who are, say, at 150 versus 200, is that the risk is high for both, but has plateaued a bit. There were about 10% of the patients in the study who had triglyceride between the 135 and 150 range. The number after treatment with Vascepa below 150 increased, but in terms of at the beginning of the study, that’s about what it was. And I forget the exact, what above and below 200, but I think it’s somewhere around 50-50, but that’s in the – actually maybe closer to 60% for the above 200 group. But again, the results were consistent across the 150 to – the 135 to 150, the 150 to 200 and the 200 and above. And that’s – that brings people into focus in on the multi-factorial effects of Vascepa, which includes lots of the things that we talked about in the past and it brings up the earlier question on EVAPORATE, which is studying one of those multiple mechanisms, so related to potential plaque’s regression, which goes beyond, in fact, stability and etc. With respect to mineral oil, you’re right, we have a frequently asked question section on our website. I will remind people that the controversies that have – some third parties have tried to create on this particular area are, driven lots of biomarker changes and those biomarkers at the beginning of those study were intentionally not primary or secondary endpoints of the study. We – they were – we’ve already done biomarker based study, but based upon the design of the study, including, that all the patients enrolled in the study needed to have LDLs below 100, in our case had mean LDL levels of 75 that regression to the mean was to be expected on certain of those biomarkers. And throughout the course of the study, the data monitoring committee has access to data relative to the placebo arms of other studies not using mineral oil, and in high-risk patient populations. We’re able to observe the LDL changes and distributions of those changes in those other studies, and at least in our view, and the data monitoring committee didn’t raise issue with them either. The results in our placebo arm were very consistent with what we saw in those other studies. At this point in time, doing an additional drug-drug interaction study, we did a bunch of those as part of this clinical program around that has been going on now for over a decade, with the FDA relative to interaction with Vascepa and lots of different drug. At this point in time, we have outcomes data. The outcomes that data is highly robust and consistent in going off and doing some form of other such study in animals are trying to running predictive. We don’t think would end providing any meaningful added value to what we’re doing. This has been looked at in lots of different ways and while we don’t think that the mineral oil has any impact, I think a lot of people have concluded, and we believe, as I stated that the analysis from the FDA get to this and we’re aware of it, has concluded similarly, that if it has any impact of that effect is very small. I know, we’re sort of at a time, I – and we did get some questions in from investors. I think we’ve answered most, and the one that we didn’t, it was about other research and development beyond Vascepa. We’re going to get approval in the U.S. here hopefully first. That’s our focus with the timelines that we’ve laid out on – at the European Commission and hopefully we’ll make advancements in the Canada and elsewhere. After we get through the approval in the U.S., we’ve got a very talented R&D team who will research some of the ideas that they’ve – that they’ve halted in the past. Then we’ll come back with some communication as to what we’re going to be working on next, but right now, there is nothing larger that we could be working on than what we’re doing with Vascepa, and we want to ensure that we provide, that’s the appropriate focus. So we’ll get back to you in the future relative to what we might be working on beyond Vascepa. But Vascepa is pretty big. So let’s get that right. With that, I think we’ve observed the time that we had set out for this meeting. I know others who wanted to ask questions. But you also have to get onto other matters as well. So I thank you for your interest, look forward to providing additional updates and hopefully we’ll have some celebration not just after the ADCOM, but particularly on or around the PDUFA date as we are looking for a label, they not just helps Amarin, but in particular will lead to the use of Vascepa to help hopefully in millions of patients, so thank you.

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