Amarin Corp. plc - der absolute Hit!

Hallo!

Meiner Meinung nach sollte die Aktie des britisch-amerikanischen Biotechunternehmens Amarin Corp. plc (NASDAQ: AMRN) ein absoluter Hit werden. Denn das Unternehmen hat, auf Basis von Fischöl, ein Medikament entwickelt, dass die schädlichen Fette im Blut (Triglyzerin) senken kann. Dabei waren die bisherigen Daten aus den klinischen Studien insgesamt absolut überragend. Kritiker werden nun einwenden, dass dies an der Kursentwicklung in den letzten Jahren nicht unbedingt ablesbar war/ist. Das ist auch soweit korrekt, liegt aber an anderen Dingen. Zunächst nämlich deuteten die vorgelegten Studiendaten von Amarin darauf hin, dass das Medikament nicht nur die schlechten Blutfette senken würde, sondern auch die guten Blutfette. Dieses "Problem" hat man jedoch mittlerweile behoben. Daher forderte die US-Gesundheitsbehörde FDA im letzten Jahr dann eine Ausweitung der klinischen Studien bzgl. dieses Medikamentes. Jedoch wohl weniger aufgrund der "Probleme", sondern vielmehr, weil man sich weitere Anwendungen dieses Medikamentes (von Seiten der FDA aber auch des Unternehmens) erhofft. Sollte sich diese Erwartung bestätigen, ist das Medikament daher ein wahrer Blockbuster mit Jahresumsätzen von mehreren Mrd. US-Dollar. Und da die US-Behörden dem Unternehmen zuletzt, in den vorherigen Jahren noch umstrittene, Patente zuerkannt haben, spricht eigentlich nahezu alles für einen positiven Ausgang (nach zugegeben langen Jahren des Hoffens (und Bangens) bzw. des Wartens). Alles in allem ist ein Investment in die Aktie daher immer noch spekulativ, ich halte diese Spekulation jedoch unter Chance/Risiko Aspekten heute für vertretbar. Erstes Kursziel dabei: 25$!!

Mehr Infos zur Aktie der Amarin Corp. plc findet Ihr auch hier, besonders die Kaufempfehlung von "hopelessly" hat mir dabei gefallen: Amarin Corp. plc - Empfehlungen. Hat sich hier vielleicht auch schon mal jemand mit dem Unternehmen bzw. der Aktie beschäftigt?

LG JoWu81

CVD Benefits in Fish Oil: Is EPA the Pearl?
Carol Peckham, Howard S. Weintraub, MDDisclosures
Jun 05, 2013

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NEJM Study on the Use of Fish Oil for Prevention of Cardiovascular Events
Looking at EPA
Other Thoughts on Triglycerides
References
Editors' Recommendations
Omega-3: Fishing Out the Recent Evidence
Fish Oils to Prevent Heart Disease
No Fish-Oil Benefit in Patients at High CVD Risk
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Looking at EPA

Medscape: So, is fish oil then also out of the question for cardiovascular protection?

Dr. Weintraub: If you were to put 50 cardiologists and endocrinologists in the same room and ask them to name 1 study in which another medicine was added to a statin and there were meaningful significant reductions in cardiovascular events, they would probably look around and not be sure. I would say that one such study is JELIS,[11-13] which was conducted in Japan and added fish oil to a statin for patients with high cholesterol (6.5 mmol/L or greater). It's important to note that the study used only EPA, with a purity of something like 94% or 96%. At a mean follow-up of 4.6 years, they observed a 19% relative reduction in major coronary events in those on EPA, although the effect on triglycerides in that trial was not dramatic. Unstable angina and nonfatal coronary events were significantly reduced. Sudden cardiac death and coronary death did not differ between groups. Granted, nobody on our side of the pond thinks that trials populated exclusively with Asian participants would necessarily indicate the same results in people in Europe or the United States, but I think it's an interesting phenomenon.

A small US company has made its own version of EPA, icosapent ethyl (Vascepa®; Amarin Pharma), which has been approved. They conducted 2 studies: ANCHOR[14] and MARINE,[15] which allowed the FDA to approve icosapent ethyl for the same indication as the other approved fish oil (Lovaza®; GlaxoSmithKline), a combination of EPA and DHA, with a ratio of about 4:3.

The MARINE study looked at people with triglyceride levels over 500 mg/dL, which represents about 1% to 2% of the US population, and the ANCHOR study looked at those with triglyceride levels between 200 and 500 mg/dL, which reflects a larger proportion -- about 20% -- of the US population. One interesting observation was that using a statin along with EPA achieved much greater triglyceride reductions than using EPA without a statin, and the stronger the statin, the better the effect. So, the interaction between EPA and statins is intriguing. Fish oils may not be dead in the water for this reason alone.


The good news is that we're going to have to wait only 2 to 4 years for answers to the question of whether EPA is beneficial in high-risk patients. An event trial with at least 50% currently recruited is looking at the concomitant addition of icosapent ethyl to therapy in individuals with documented cardiovascular disease and/or diabetes.

I certainly haven't seen any studies in major journals on any comparative difference between the DHA/EPA combinations and the EPA-only agents. However, if you look at the FDA's Pharmaceutical Inspectorate (PI) for Lovaza, and in most of the data that the company has compiled, there is an average net increase in LDL cholesterol. Obviously this can turn some people off. We almost get the same kind of information that was out there with rosiglitazone, when, if you remember, LDL was increased in many of its studies. So, whether this mattered or not, certainly LDL is one of the few things in the lipid world that we have relative agreement on, that it is bad for you. There are some very interesting theories floating around, but I think that being LDL neutral and reducing inflammatory markers and triglycerides, as is indicated in the MARINE and ANCHOR studies on EPA, may be the difference in how these fish oil drugs behave.


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June 18, 2013 12:13 PM EDT     Send to a Friend
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Price: $6.60 -0.3%

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MKM Partners analyst Jon LeCroy weighed in on Amarin (NASDAQ: AMRN) Tuesday following news that NCE status on Vascepa was once again delayed. LeCroy said the NCE delay does have a silver lining, however.

"Obviously NCE designation is the preferred outcome but we view continued delays as better than no NCE, as delays effectively prevent Paragraph IV filings," the analyst notes. "While a lack of NCE designation is delaying generic filings, it also is perceived as preventing an acquisition of the company and Amarin shares may remain under pressure until an NCE decision is made. We expect the next
Orange Book update for June to occur around July 12."

The firm notes Vascepa prescriptions continue to grow but are running slightly below their previous estimates and they are slightly lowering 2013 and 2014 revenue and EPS estimates. That said, the firm views the 2013 consensus Vascepa revenue estimate of $57.4mn as "easily attainable."

LeCroy cut 2013 and 2014 revenue estimates to $68 million and $254.9 million, from $73.6 million and $263.7 million, previously. The firm's 2013 and 2014 EPS estimates are ($1.51) and ($0.82) from ($1.49) and ($0.78), previously.

The firm reiterated a Buy rating and price target of $12 on Amarin.

For an analyst ratings summary and ratings history on Amarin Corporation click here. For more ratings news on Amarin Corporation click here.

Shares of Amarin Corporation closed at $6.62 yesterday, with a 52 week range of $6.25-$15.96.

"In considering the results of the ANCHOR trial, the presumption has been that improving various lipid parameters will translate into a reduction in cardiovascular risk. With rare exception, FDA has historically considered granting approval for lipid-altering drugs based on favorable changes in the lipid profile, with the assumption that these changes would translate into a benefit on clinical outcomes."

REDUCE-IT, once complete, will finally back-up the assumptions but AT THIS TIME IS NOT REQUIRED FOR ANCHOR APPROVAL.

From page 87:

"The applicant-sponsored cardiovascular outcomes trial, REDUCE-IT, which is studying patients at high-risk for cardiovascular disease at LDL-C goal on statin therapy with residually high triglycerides (TG ≥200 mg/dL to <500mg/dL), intends to confirm this implied benefit."

Wake up people. Arent you tired of swallowing bear shit?

More significant, to my mind, is the lack of any evidence for any important improvement in clinical outcomes that can be tied to Vascepa. Now some people believe that ANCHOR provides enough data to justify the expanded indication, as it technically met its primary endpoint and reduced triglycerides. The argument here is that improvements in lipid parameters have traditionally been accepted by the FDA, and that there is no current approved and effective treatment to treat high risk people with moderately elevated triglycerides.

The counter-argument against approval is made clearly and strongly in the FDA briefing documents. Although the FDA agreed to the ANCHOR protocol, it also specifically noted that the interpretation of the trial would clearly depend on the results of several large ongoing outcomes trials testing the hypothesis that non-statin therapies (nitrates, fibrates) would reduce residual risk. Since that time the results of these trials have been published and they have uniformly failed to demonstrate any clinical benefit. Although the FDA notes that these trials have been controversial and are subject to different interpretations, the burden of evidence now remains on those wishing to prove that reducing residual risk with non-statin therapies is beneficial.

An apparent contradiction to  this perspective is the fact that the FDA has actually approved a number of lipid and diabetes drugs in recent years based on surrogate outcomes. An example is the approval of 2 new drugs from Aegerion and ISIS to treat people with extremely high cholesterol levels due to homozygous familial hypercholesterolemia. Although these drugs raised all kinds of red flags over both safety and efficacy, the FDA advisory panel members and the FDA itself ultimately decided in favor of the new drugs.

The decisive argument in these cases was that physicians needed as many options as possible in treating patients. This principle trumped concerns about the lack of outcomes. But there’s an important reason why this argument may not work in the case of Vascepa.

No matter what the FDA decides now, Vascepa will be available as a treatment option to physicians. Since it is already approved, physicians will still be able to prescribe it for off-label usage. The main effect of a negative decision would be to prevent Amarin from marketing and promoting the drug for this off label usage.

The fact that Vascepa is already on the market provides cover to the panel members. They will be less likely to make a recommendation based on the emotional appeal of expanding physician options and more likely to take a strong stance in favor of outcomes trials. The most likely scenario is that they will withhold approval of an expanded indication until the results of  REDUCE-IT, Amarin’s outcome trial with Vascepa, become available in 2016

Cash R&D was around $17 million last quarter. If you cut that in half to $8.5 million and reduce the $30 million cash SG&A to $25 million, you get an overall reduction in cash burn discussed thus far of $20.7 million using the most optimistic of scenarios imaginable.

Amarin, even then, is still at a $32.1 million quarterly cash burn. While Q3 results aren't out yet, let's assume the $52.8 million burned last quarter comes down to $40 million. That leaves Amarin with $230.50 million left. $230.5 million divided by $32.1 million = less than 8 quarters. This time in two years, Amarin is broke.

Amarin gave no details in its most recent conference call to expect anywhere as rosy of a scenario of reduced cash costs as I presented. Of course, there's always the buyout possibility, especially if another company with better resources believes it can market Amarin's Vascepa better than Amarin did. If sales go up sixfold instead of my "optimistic" threefold, cash burn would go down another $7.2 million (at 60% margins). Still, even at a sixfold increase and all the other rosy scenarios, it only buys Amarin time, not success, of another two quarters. It really needs a massive sales increase to even break-even, one that has a great chance with ANCHOR approval. Short of a buyout, or severe dilution, or an angel lender, I'm afraid Amarin is broke fairly soon without ANCHOR approval. It's do or die time. Amarin has no other drugs in its pipeline. Good luck to all.

Commenting on the seven potential 'Yes' votes, Wei says: "We count four likely Yes votes (Dr. Seely, Dr. Wilson, patient rep, consumer rep). Dr. Seely has the most positive voting record of any panelist in this division,and the reps have shown a natural bias to increased patient access to new drugs. We found comments from Dr. Wilson on the importance of TG as an important CV risk marker and support for surrogate endpoints. We favor a Yes vote for Dr. Hiatt following strong opinions on post-approval CV outcomes testing in other diseases, but we remain concerned about one negative comment on the utility of lipid endpoints for another TG-lowering drug. We are leaning to a Yes vote for Dr. Everett, although he has participated in only one prior panel and his commentary had limited relevance to AMRN's situation. The biostatistician is another tenuous Yes prediction, as he is new to FDA panel meetings, so we base our analysis from past biostatisticians who have generally voted in favor of drug approvals and post-approval CV outcomes testing."

On the three likely 'no' votes, Wei comments: "All three predicted No votes (Dr. Smith, Dr. Cooke, Dr. Gregg) were difficult to call, but we were influenced by commentary in all three cases indicating a bias against surrogate endpoints. That said, the actual votes from these three panelists were generally positive, and for the two panelists on an obesity drug panel, they both voted for approval on the basis of weight loss as a surrogate endpoint."

Wei maintained a Buy rating and $20 price target on AMRN.

The FDA agreed with Amarin in 2008 that the company needed to have the cardiovascular outcomes trial under way, not completed, when it sought approval for people with high triglycerides. The agency rescinded the accord Oct. 29 based on recent clinical trials and meta-analyses that have failed to confirm a heart benefit from lowering lipids.

Appeal Ruling

Amarin said today that the FDA will relay its decision on the appeal by Jan. 15. The regulator hasn’t indicated when it will rule on the application to expand use of the drug, the company said.

Triglycerides and cholesterol are separate types of lipids, or fat in the blood, according to the Mayo Clinic.

Amarin, run from Bedminster, New Jersey, sought approval for the drug to treat patients with high triglycerides who also are taking cholesterol-lowering statins.

GlaxoSmithKline Plc (GSK)’s fish oil pill Lovaza was approved in 2004 for patients with very high triglycerides. Very high triglyceride levels measure at least 500 milligrams per deciliter. High triglycerides are those from 200 milligrams to 500 milligrams per deciliter.

Stores such as GNC Holdings Inc. (GNC) and Vitamin Shoppe Inc. (VSI) sell non-prescription dietary supplements containing fish oil. It would take 10 to 40 of such omega-3 capsules to equal the pure fatty acid obtained from “wild deep-water Pacific Ocean fish,” according to the company’s website for Vascepa.

To contact the reporter on this story: Anna Edney in Washington at aedney@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Prior to being able to appeal DMEP's October 2013 decision to rescind the ANCHOR SPA agreement, FDA protocol requires that DMEP first be given a formal opportunity for reconsideration. With that step now completed, Amarin plans to appeal the DMEP decision to the FDA Director of the Office of Drug Evaluation II (ODE-II), the next level under FDA dispute resolution guidance. Based on information available to Amarin, Amarin does not expect a determination on the pending ANCHOR supplemental new drug application (sNDA) while Amarin prepares its appeal or while this appeal is pending. Amarin also plans to continue its efforts toward a positive determination on the pending ANCHOR sNDA.

As previously stated, Amarin recognizes the significant challenge it faces in its efforts to reinstate the ANCHOR SPA agreement and obtain approval of the ANCHOR sNDA. There can be no assurance that Amarin will be successful in its effort to reinstate the ANCHOR SPA agreement or obtain a label expansion reflecting the ANCHOR clinical trial. There also can be no assurance that the FDA will not communicate the results of its review of the ANCHOR sNDA prior to the timing expected.

Vascepa remains FDA approved for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe (>=500 mg/dL) hypertriglyceridemia.

Conference call today

Members of the Amarin management team will host a webcast and conference call to provide a company update and discuss the recent FDA action today at 8:00 a.m. ET.