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Yep it’s a possibility even if people want to bury their heads in the sand and pretend it’s not.
I am still holding all my shares but Denner’s silence concerns me.
Not frustration talking, just providing some balance to your assessment which conveniently left this option out.
We all want this to bounce back but let’s be realistic as well. Denner bailing may not be likely, but only a fool would say that’s not a possibility.
You forgot another possibility: That he is fed up and looking to dump his position and get out.
I hope this isn’t the case, but it can’t be discounted. BB already cut bait, and I can’t say I blame them.
Yeah I am not sure what to think of the supposed formulary changes, but it's hard to think these morons in management are getting out in front of any additional obstacles coming our way. They are smug and 100% tone deaf, and I wish Denner would boot them all out.
I agree Denner's silence is deafening and it makes me nervous. It is either a) tacit approval of what is happening now or b) calm before the storm (special meeting or him exiting his position). It is weird that it's been 2 months since he initiated the special meeting and nothing since. Hard to say what is happening, but I do think we'll know in 1Q 2023 either way. There is also the matter of this "announcement" KM has promised to make in 1Q or 2Q regarding the combo product, but it's hard to get too excited about that, based on previous track record. Hopefully he'll surprise us.
And China approval...WTF? That was supposed to happen over a year ago. I have no words for that.
No offense to others, but anyone predicting a price target above $6 or $7 is not living in reality. I stand by my original comments that we'll be lucky to hit $3-$4 anytime soon. Trust me, I would love to be wrong.
Hey MRM, I bought some down here after the initial crash around $1.30 or so, but haven't added shares in a while, and don't plan to add any more at this point.
I am still holding all my shares and don't plan to unload anytime soon, but do have serious questions if the company can dig themselves out of this hole. On a brighter note, I don't see a whole ton of downside, especially now that these idiots have stopped the ridiculous cash burn. I would be very happy if this gets back to $3-$4 range, and anything above that would be somewhat miraculous IMO. Increased EU revenues are the only thing that will move this up, and we have the Denner wildcard too - I think we'll know what's happening there soon, probably 1Q 2023 at latest.
Like you, I'll be selling covered calls when my January 2023 $10s expire. Selling covered calls is literally the only intelligent thing I've done with regards to this soul sucking investment.
Agreed - he just needs the majority vote. Lot of misinformation out there.
Good luck MRM. I bought some more ~$1.20 a month ago, but can't bring myself to add any more. I do agree $5 is a good exit point (even if slightly below my cost basis). $7/$8 isn't impossible, but seems unlikely anytime soon. Anyone talking about $10+ price targets is out of their minds IMO.
I will also be selling calls in January when my 2023s expire. Selling covered calls is pretty much the only smart thing I have done as it relates to this investment. Which ones are you looking at? I am thinking of $5/$7s for Jan 2024 myself.
OY
Yes, with the majority of votes at the special meeting, he can remove the entire board and replace them with his people if he wanted to. Hopefully that’s the direction this is heading.
New data might have led to a different result for Amarin fish oil drug, FDA panelists say
Two members of an expert panel that recommended the Food and Drug Administration approve a fish-oil-based heart drug, Vascepa, said recently released data would have led them to reconsider their votes.
The concern stems from the suggestion that a substantial benefit the drug showed in a large clinical trial might have been in part due to harm caused by the placebo it was compared to in the study. A new analysis published in the medical journal Circulation on June 28 indicated that in the group that received the placebo, which contained mineral oil, volunteers had blood test results that might indicate heightened risk of heart attacks and strokes.
The experts’ comments raise concerns not only about the use of one drug, but about processes at the FDA and the future of fish-oil-derived medicines as heart treatments. They are a further headache for the drug’s maker, Amarin, which is also facing generic competition in the U.S. for Vascepa, its only product.
“Certainly this changes my interpretation of the potential harms of mineral oil placebo,” said James de Lemos, a professor of medicine at UT Southwestern in Dallas. He is an editor at Circulation but was not involved in the review of the recent paper. “This recent paper clearly shows that this mineral oil placebo is not inert, it’s not a placebo. If we had known this during the panel, that would have affected our assessment of the study result.”
De Lemos added: “As a clinician, it really leaves me at a loss. I really don’t know what to do with this drug anymore.”
Marvin Konstam, the chief physician executive of the CardioVascular Center at Tufts University School of Medicine, echoed those concerns.
“I think I might well have voted differently,” Konstam said. “I’ve been on innumerable panels and innumerable data monitoring committees. I can’t remember a situation like this where retrospectively there was a question about the risk of the placebo.”
The November 2019 hearing of the FDA advisory committee had a big impact on Vascepa use. Between 2019 and 2021, prescriptions for the drug or its generic counterpart increased 45% to 3.3 million, according to data from health information firm IQVIA. In the first five months of 2022, 30% of prescriptions were generic.
At that advisory committee meeting, 16 panelists voted unanimously to recommend the agency approve Vascepa to reduce the risk of first heart attacks and other heart problems in patients with high triglycerides.
It was known then that patients receiving the mineral oil placebo had increased in LDL, the so-called “bad cholesterol,” and C-reactive protein, or CRP, another blood test result that is an indicator of cardiovascular inflammation, which also indicates a risk of heart attacks and strokes. But the FDA presented its own analysis arguing that the changes in LDL and CRP could not explain the substantial benefit seen in the Vascepa study.
“I think most of us in the room were in virgin territory, and we’re taking in the information as we did, and we all had a certain trust in the FDA,” Konstam said. “And I had a willingness to accept what came out of their assumptions as pretty reasonable.”
But Konstam said that even as the panel ended he began to have doubts about whether the mineral oil placebo could explain all or some of the drug’s benefits. Perhaps a small, daily dose of mineral oil could be interfering with the absorption of cholesterol-lowering medicines. But what, Konstam wondered, if it were interfering with other medicines, too?
Other hypothetical explanations have been offered, too. Mouse data indicate that chronic mineral oil use may allow toxins produced by bacteria in the gut to enter the bloodstream. The Cleveland Clinic’s Steven Nissen, who is a critic of the use of mineral oil in the Amarin study, is a co-author of the paper.
Whatever the reason, Konstam said, modeling how much of the result of the study is due to mineral oil and how much is due to a benefit from Vascepa is a difficult prospect, and only becomes more difficult with more data. There is a vast amount of data on how changes in LDL affect heart risk, but it is more difficult to create a model for some of the other blood test results that were heightened in the results published in Circulation.
For instance, in the mineral oil group, blood levels of interleukin-1ß, a protein involved in inflammation, increased 28.9%. In a previous study by the researcher who led the new analysis, Paul Ridker of Brigham and Women’s Hospital in Boston, a drug that targeted Interleukin-1ß reduced the risk of heart attacks and strokes by 14%.
“Whether that negates the results of the study or mitigates the results to sort of discount the effect, who knows,” said de Lemos. “I think the trial result was always implausibly large. The magnitude of the risk reduction was frankly very surprising. My guess is it’s somewhere in between, that there may be a beneficial effect of the drug that’s magnified by the effects of the mineral oil placebo.”
In a statement, Amarin said it was “very surprised” that members of the advisory panel would comment based on the Circulation paper and said that the company stands behind its pivotal trial of Vascepa.
In an interview, Steve Ketchum, Amarin’s president of R&D, said that the company does not believe that there is new evidence that mineral oil, not Vascepa, could explain the differences seen in the study. He said that in absolute terms, the blood test results in the Circulation study did not change enough to explain the benefit. “We think that it’s also important to look at the absolute changes and in our view they are small and they do not correlate to any meaningful changes in outcomes,” Ketchum said.
Ketchum also said that important analyses were not accepted as part of the circulation manuscript. He said those concerned by the results “do not have the benefit of seeing the more complete information. That’s what gives us confidence.”
In an editorial accompanying the Circulation paper, Robert Harrington, chairman of the department of medicine, wrote: “The hard reality is that we are left with uncertainties and the questions raised by use of the mineral oil as placebo can only be answered by another [randomized controlled trial].”
Another member of the panel, Susan Ellenberg from the University of Pennsylvania, said that her expertise was in statistics and she would defer to experts in cardiology on the new effect, but that any analysis could, of course, have affected her vote. Several other members of the panel did not return requests for comment.
Scientists have thought fish oil preparations might reduce heart disease for decades, since experts hypothesized that the omega-3 fatty acids in fish explained surprisingly low rates of heart attacks in the Inuit. Even that claim has come to be questioned since. Many clinical trials have failed to show a benefit of various fish oil preparations. One that did, conducted in Japan, used a preparation that only included one very specific omega-3 fatty acid – eicosapentaenoic acid, or EPA.
Amarin decided to develop its own EPA-containing fish oil supplement more than a decade ago. Initially, like other prescription fish oil supplements, the drug was approved to treat patients with very high levels of triglycerides, or particles of fat in the blood. At very high levels, triglycerides can cause pancreas problems; lower elevated levels may mean patients have an increased risk of heart disease.
Issues about the mineral oil placebo were raised at FDA advisory panels that discussed earlier trials. But Amarin chose to use the mineral oil placebo in its major trial, with the FDA’s approval, because it closely resembled Vascepa in appearance.
De Lemos and Konstam, along with other cardiologists, say that another clinical trial may be required to settle questions of Vascepa’s benefit. But it seems unlikely that Amarin will conduct such a study, which would cost hundreds of millions of dollars. The company likely does not have the money.
Amarin’s shares on the NASDAQ have fallen more than 94% from their December 2019 peak.
“The FDA is aware of the publication,” an agency spokesperson said in a statement. “In general, the FDA does not comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
But questions around Vascepa also have larger ramifications for the FDA because in recent years there have been cases where critics have worried that the FDA has gone too easy on companies, resulting in big unanswered questions about new drugs. For instance, a new muscular dystrophy made by Sarepta was approved in 2016 based on levels of an important muscle protein; six years later, data confirming the drug’s benefit are still not available.
Last year, the agency overruled one of its advisory committees to grant accelerated approval to Aduhelm, a new Alzhiemer’s drug. Before the advisory committee meeting, the FDA had taken the unusual step of presenting a single document from both the agency and the drug’s maker, Biogen, instead of two independent analyses of the data.
HDG, I think these are all good points, but still think overall shareholder sentiment has to be considered unfavorable considering the drastic collapse in SP.
I definitely agree the exclusivity agreements in US were a smart move, and it seems to have stopped/slowed the erosion. The reduction in US workforce was a good move too, but I feel they waited too long, and it should have been done earlier.
I think EU is "wait and see" as they finish reimbursements and have a full year of launching next year in several EU member states. Hopefully that will be the start of significant contribution to revenue from EU. Still a long road ahead.
Thanks for the numbers Raf.
At the last earnings call, KM mentioned that we should see "stabilization" soon based on their exclusivity agreements aimed at retaining business and stopping the erosion.
Are we now seeing this around the 63-65k range?
Thanks HDG. It’s confusing based on Denner’s wording in the PR.
If he does call a meeting, I agree that it will be a close vote based on the AGM voting. But considering current sentiment towards Amarin management, I think Denner’s proposal to add representation could swing some additional votes his way. I think his best play is to propose to replace the least popular Director (probably Ekman) with his designee. It seems he wants to add multiple Directors, so he may need a couple “weak links”.
This is a good point/question and something I have been wondering about too, based on the wording you mentioned in Denner's press release.
From a quick look, I think this process is covered by UK Companies Act 1948 - I found the following :
"Since the Companies Act 1948 UK shareholders have had the right to remove all or any of the directors at any time by simple majority vote (and relatively easy mechanisms for convening shareholder meetings against management wishes have been available to them)"
The entire legislation is here: https://www.legislation.gov.uk/ukpga/1948/38/enacted
Off a quick review, I think it just 50% of the votes that are cast, not 50% of the OS. But need to look at it closer.
Yes it's the full article. The other info you are looking for is publicly available - look it up.
Hit piece - in case anyone wants to read...
A new analysis of Vascepa, a medicine derived from fish oil and used to prevent heart attacks in a select group of patients, raises big questions about the evidence that the medicine is effective. Several experts say the questions require a new clinical trial to be conducted, and some even say the Food and Drug Administration should reconsider the product’s approval.
In a twist, the new data come from an analysis funded by Amarin itself.
The results “raise the concern that the apparent lowering of cardiovascular risk observed with icosapent ethyl may —in fact — have been an increase in cardiovascular risk with the comparator, mineral oil,” said Gregory Curfman, deputy editor at the Journal of the American Medical Association, using the generic name for Vascepa.
Here is what happened. In 2018, researchers working with Amarin presented results from a five-year, 8,179-patient study, REDUCE-IT, that showed giving Vascepa to heart patients with elevated triglycerides reduced the rate at which a combination of cardiovascular problems – heart attack, stroke, procedures to unblock arteries, and chest pain – occurred from 22 per 100 patients to 17 per 100 patients. That’s a 25% reduction.
That study led the FDA to approve Vascepa, which was previously used only to lower extremely high triglyceride levels, in a much broader population to treat heart disease. But critics always had a concern.
As a placebo, Amarin had chosen to use mineral oil because it closely resembles Vascepa in appearance. But there were concerns, because in the mineral oil group, levels of two proteins in the blood that raise the risk of heart attacks and strokes went up. They were low-density lipoprotein, or LDL, the so-called bad cholesterol, and C-reactive protein, or hsCRP, a measure of inflammation in the body.
That raised the concern that the study wasn’t showing that Vascepa prevented heart attacks, but that mineral oil caused them — or at least that the drug’s impressive benefit might be blunted by harm caused by the placebo. The FDA considered this possibility, but decided that the effects of mineral oil were unlikely to account for the positive result.
In the new study, Amarin funded Paul Ridker at Brigham & Women’s Hospital, a well-known scientist who pioneered the use of hsCRP as a blood test to measure cardiovascular risk, to re-analyze blood samples taken from patients in the REDUCE-IT trial to see how levels of other chemicals that have been connected to increases in cardiovascular risk changed.
Those are the new results, published in Circulation, a medical journal. They show that for every one of seven different measures — including two other measures of inflammation and several different ways of measuring harmful cholesterol levels — blood levels worsened in the mineral oil group over a period of more than two years. But levels in the group that received Vascepa did not budge.
The paper says that these kinds of changes were not seen in the control arms of other trials Ridker’s laboratory had analyzed, including a pivotal study of the cholesterol drug Crestor, a study testing the rheumatoid arthritis drug methotrexate for its heart benefit, and a trial of a different fish-oil-derived medicine that used corn oil, not mineral oil, as a placebo.
The paper concludes ‘the effect of these findings on interpretation of the overall risk reductions in clinical events observed within REDUCE-IT is uncertain.”
Ridker declined to comment on the paper, directing all questions on the article to Deepak Bhatt, also a cardiologist at the Brigham, who was a lead investigator of the REDUCE-IT trial and is listed as senior author on the new publication.
Bhatt wrote in an email that the new biomarker data are “highly correlated” with the already known changes to LDL and CRP. He said that these biomarker changes “don’t really provide any additional mechanistic insights into the clinical benefits seen in the trial,” which he says were driven by a 400% increase in levels of eicosapentaenoic acid, an ingredient in fish oil.
When asked why this conclusion differed so much from the published paper, Bhatt replied, “Such are the vagaries of peer review.”
He said the authors submitted “several external analyses” that were not retained by journal editors and outside reviewers in the final version of the paper. “The full set of analyses provide a more balanced perspective, but I suppose we will now have to publish those elsewhere and later.”
Ridker’s silence and Bhatt’s comments give the impression that the editing of the paper may have been contentious.
Amarin said in a statement that analyses like this are meant to explore new hypotheses, and expressed its confidence in the original result.
But Sanjay Kaul, a frequent FDA adviser and researcher at Cedars-Sinai Medical Center in Los Angeles, basically agreed with this analysis, saying “any such impact is unlikely to materially dilute the overall robust evidence of benefit in REDUCE-IT.”
Other cardiologists were more concerned by the new data. Curfman noted that the study did not measure potentially beneficial markers, and that inflammatory chemicals in the blood are what are known as surrogates, which are seen as less trustworthy than hard outcomes like heart attack. Still, he said, the only way to know if Vascepta is reducing cardiovascular risk is to run another study.
“If Amarin intends to stand behind icosapent ethyl as a beneficial clinical product, it should sponsor such a trial,” he said.
Other experts were even more concerned.
Steven Nissen, a cardiologist at the Cleveland Clinic, ran a study of a rival fish-oil-derived product from AstraZeneca — the study that used corn oil as a placebo. In that study, there was no benefit. He has previously raised concerns that mineral oil may not have been a good choice as a placebo, and he said the new data raise further concerns.
“These findings are the closest thing I’ve seen in a long time to a smoking gun,” Nissen said. A broad range of inflammatory and lipid markers associated with atherosclerosis changed for the mineral oil group, but not the Vascepa group. When the FDA reviewed the study, the agency just had data on hsCRP and LDL. For other so-called biomarkers, such as Lp-PLA2, a cholesterol-related protein some companies are targeting with drugs, to go up as well raises more concerns.
“I think if you read this in totality it leaves open a major question whether REDUCE-IT is a false positive or not and I believe FDA should re-review the label to see if it is appropriate,” Nissen said. “I do not believe physicians should use icosapent ethyl without a study using a neutral comparator such as corn oil.”
“I think this is all the more important because it’s being written by the people who did the trial and what they said, in their words, is that this throws into doubt the results of the original study,” said Harlan Krumholz, a professor of cardiology at Yale University. “This is important news that has to get to patients and doctors.”
Krumholz, who is Ridker’s brother-in-law but was not involved in the trial, said that the result “is sufficiently important that the FDA should re-review its initial decision and the guideline recommendations should be re-visited.”
Despite pleas from experts that Amarin run another large and expensive trial, that is now unlikely. The company is currently facing generic competition for Vascepa in the U.S., and its first quarter revenue fell 34% to $94 million in the first quarter of 2022. Given that cardiovascular outcome studies can cost hundreds of millions of dollars, the company is unlikely to fund one. A trial would likely have to be funded by the National Institutes of Health or some other public source.
Such a study could help solve a giant medical mystery — whether fish oil drugs can help prevent heart disease. Researchers have been fascinated by the potential of the compound, and the omega-3 fatty acids like the EPA in Vascepa, since the 1970s when researchers postulated that they might explain low rates of heart disease among the Inuit. Just about every piece of research since, including that original paper, has been contested. Large clinical trials have mostly not shown a benefit to fish oil pills. One exception, though, was for a product similar to Vascepa that showed a benefit in a Japanese trial.
It had originally appeared that the Vascepa study had at last provided a positive answer, that a type of fish-oil-derived medicine could prevent heart attacks at a high dose. Instead, it has only deepened the existing mystery.
Yep I saw the same. And with that huge number of abstains, there must’ve been big support from other institutional holders, including Baker Bros.
I am wondering who accounts for the majority of these 94M broker non votes?
I just did the same. I think it will send a clear message.
This is getting interesting. So are folks going to vote “Abstain” as well to align w/ what Denner is doing?
It’s great he has the power to call a meeting at any time to replace our worthless BOD. It’s not just an annual meeting thing.
Thanks, sounds like we’re looking at similar options. Agree the current prices are not great though.
MRM, if you don’t mind me asking, what strike price and dates are you looking at? I’ve been looking at both the $3/$4 Jan 2023s and also the $7 January 2024s. My cost basis is just under $8.
The premiums are not overly exciting, so hoping for a near term boost to increase them. Not holding my breath though. I think the earliest we might see a jolt is next earnings call, if the company can demonstrate they aren’t destroying our balance sheet.
68,886
MP, nice DD and thanks for sharing this.
At face value it makes sense. But personally I have never heard of this before as a rate limiter in getting PR. I also asked a friend who interacts directly w/ FDA and he said the same.
Doesn’t mean it’s not true. But very likely Elisabeth is just going off information from the internal team at Amarin. That may be their hunch, but nobody knows for sure until FDA communicates the decision.
Interesting times!
HDG, I agree- it’s a weird situation.
They could use a 3rd party (e.g. a CRO) to submit the application, or do it themselves. In either case, the process of filing the EU application is not a huge operational burden, b/c they’ll use the US sNDA filing as the starting point. Just as I’m sure HLS did in preparing and filing the CA submission.
I think you are right that a partner will be required down the road for commercialization purposes (assuming no BO). Maybe lack of a partner and/or BO discussions are contributing to the delay. It’s hard to say.
Kiwi, I don’t think so, only b/c JT recently stated they were “hoping to have submitted in Europe sometime towards the end of the year”.
IMO requesting accelerated assessment and waiting for decision would not delay the submission to end of 2019. Something else going on.
Yeah I’m as baffled as everyone else. Similar to Canada, the submission package to EU would be heavily leveraged from the US submission. It’s very common for companies to submit simultaneously in all these regions (ie US, CA, EU) b/c of the common dossier format they share.
We submitted very quickly in Canada, but are taking our time w/ EU for some reason. Dunno why.
I agree, nothing is ever a slam dunk w/ FDA. Including priority review. I think we’ll get it, but wouldn’t be shocked if we did not.
Chance of rejection due to a technical issue, or incomplete application would be very low.
That is correct. If we get PR, *should* hear this week.
Outside chance we hear on day 61, due to holiday on Monday. But I doubt it.
Their stated target on fda.gov is 60 calendar days to inform sponsor of priority review. Seems pretty clear to me.
It’s also consistent with what I’ve seen in practice. But to each his own I suppose.
Not sure what that other document is, but FDA guidance on their web site states 60 calendar days:
“FDA informs the applicant of a Priority Review designation within 60 days of the receipt of the original BLA, NDA, or efficacy supplement.”
BB increased their position by 1% in 1Q 19
https://whalewisdom.com/filer/baker-bros-advisors-llc#tabholdings_tab_link
VuBru, sorry for the delayed response. Regarding your question: I'm honestly not sure what influence that would have, but I do think an AdCom is likely in either case.
I am basing this on the indication Amarin is seeking, and also previous comments made by Amarin, where they have guided to an AdCom.
Obviously just speculation on my part. We should find out soon either way.
Based on Canada NDS PR, sounds like they are looking for a pretty broad label...
“The NDS seeks an indication for promotion of Vascepa in Canada to reduce the risk of major adverse cardiovascular events (“MACE”) in statin-treated patients with elevated triglycerides and other risk factors...if approved, Vascepa will be the first drug approved in Canada for this indication.”
Oneragman, sorry for the delayed response.
I do not believe supply issues have any bearing on the EU submission one way or another. Amarin (like all companies preparing to bring a drug to market) has been planning their regulatory strategy years in advance of this. Because of the similarities in dossier content and format, US and EU are almost always submitted in tandem w/ one another. So I can’t see how they wouldn’t be prepared to meet demand in the two biggest markets in the world, seeing as they’ve been planning this for years.
I think their silence on the topic is nothing more than gamesmanship.
IMO, if Amarin does not file the EU submission by this next deadline of June 3, or at the very worst July 1, they really screwed something up.
I don’t buy it. I think they’ve been coy on EU activities all along, and this is more of the same.
We know that operationally it’s possible to submit US/EU submissions within days of each other. So the fact it’s already going to be 2 months is ample time. And they are losing revenues each additional month they wait to file in EU.
It could come earlier, but my assumption is it will be around one of those milestones, depending on the type of review we receive. And we will learn of AdCom (if applicable) in parallel.
No PR and an AdCom is a potential scenario that could cause a short term drop. I would think. Although as others have pointed out, this stock seems to trade opposite of what we expect :)
We’d likely learn of an AdCom at day 60/74.
BB, I noticed the same- the action on June 21 options seems pretty robust.
I agree it makes sense when you think of the upcoming regulatory events/catalysts, Priority Review decision in particular. But don’t sleep on EU submission either. I still expect them to submit by June 3 deadline. Do you think folks are expecting it that soon? I think it will surprise, w/ most not expecting EU filing until late 2019 IMO.
These two potential major catalysts do make upcoming options interesting.
Have you noticed the open interest on June 21 calls? I’m not an options expert by any means, but that jumped out to me.
You guys raise an excellent point: it can’t come on day 60 as that’s a US holiday. I completely missed that myself.
We should expect it that following Tuesday (day 61), or (hopefully) the previous Friday, if FDA is conscientious enough to hit their 60 day deadline.