Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
In 2013 FDA carefully crafted an ambiguous voting question. When a panelist asked for it to be clarified early in the meeting, clarification was postponed until immediately before the vote, after Amarin’s presentation and virtually all discussion. The “clarification” fundamentally changed the question, sidestepping legal requirements to inform Amarin and its investors in advance.
MO is not a very wild card IMO. Can anyone name a single credible expert who, after reviewing the facts has said that MO could possibly have impacted RI’s RRR estimates by more than about 3%? I looked at it in depth and found no one who claimed the impact was even 1% or could possibly be 1%.
MO issue was addressed and resolved years ago, triple confirmed recently. It will be raised at adcom so panel can opine and relieve FDA of some of the responsibility. There is no perfect, or better, placebo. Corn oil is active, raises AA, and EPA/AA is one of the best causal CVD risk factors.
I’m surprised to see that article say that an EPA/DHA blend raises LDL for those with very high trigs but not for those with just high trigs.
I expect FDA to probably raise several questions they already know the answer to, to get the panel on the hook to share responsibility, including MO and hs-CRP. Both pretty much already settled by the SPA. The issue of substance at panel is the extent of label expansion. The case to include those at risk independent of statin or strict trig limits seems strong, but I could easily see FDA limiting it to the RI cohort. Or not. Whether voting questions include extra wide label will be telling IMO. Narrowest conceivable label will still be plenty wide, and some will likely continue to take it off label if necessary, as I have done for years.
I also got V through UHC for $9/mo with trigs between 100 and 135 for years, before RI top line results, in Virginia, with absolutely no resistance. Ditto for Aetna when we switched a couple years ago. We have a pretty generous plan through a large corporate employer.
MTNB is years from having Marine label (if ever) let alone expanded for CVD, and their stock price does not reflect market belief they ever get there, for a bunch of good reasons. They have recently hired a high powered advisory committee as part of a recent effort to coat tail AMRN, but not even they can make a silk purse from a sow’s ear. The past trial they tout was tiny, unpublished, and deeply flawed.
Great post. For those new to this, I believe there is a typo, should read “DHA does not possess”
A minor injury such as a skinned knee before a blood draw can spuriously raise CRP immensely (possibly factor of a thousand). Using log CRP mitigates that so it’s standard practice and was pre-specified by FDA. Log CRP was within pre-specified requirements and is a non-issue.
MIn oil was put to bed a very long time ago, for those few who ever thought it was out of bed. It seems very likely to me this is about FDA being glacially slow and not giving a sh!t about people needlessly dying by the thousands a few months longer, let alone caring about being fair to Amarin and its long suffering shareholders.
I’m not getting my tin foil hat out of the closet just yet, but if I did, the excuse would be that it’s hard for the cynics amongst us not to notice that it would be worth a lot to GS and others looking to load up cheap to have an adcom announced far later than should reasonably be expected.
Upside- a possible explanation is adcom was added to consider a broader label. Not going to bet on that, but possible.
I want one of those hats, badly.
I remember thinking the Eastern European subjects (Ukraine etc) would boost RI performance because of their poor health and high event rates. Last August or so, when JR complained some locations weren’t turning in their results when due, I suspected those folks might be irresponsible or even holding out for a bribe. (I was a bit surprised at the tenish percent failure to complete rate, and also suspected our Ukrainian friends.) The sharply lower RRR when there was a good case for higher makes poor compliance seem likely.
I’m at beach and can’t check if this was mentioned anywhere , but I’d love to see results filtered by compliance, and how much closer omitting obvious very poor compliers would get us to the very RRR I predicted based on JELIS. Some of the discrepancy was due to more deaths for RI, but RI still had very low RRR per gram of dose relative to JELIS adjusted for known trial differences, especially considering the already low JELIS event rates.
Not much to complain about with 25% RRR, but 35-40% still feels about right to me somehow.
There’s a wide range of attitudes among doctors. I was lucky my doctors were interested to learn when I discussed V with them years ago and were willing to prescribe based on safety and plausible story on benefit, before RI. My wife’s doc is a stickler, won’t do it off label even after RI and total events and ADA, no real reason given other than notSOC. We both have enough risk to care about from age (60ish).
I think approval and SOC from AHA, ACC will help a lot. RI is the second trial due to JELIS and the extra high stat sig.
OT, I saw the millionth Cologuard kit at EXAS corporate headquarters recently. I had hoped to talk to someone about an algorithm improvement I developed that I’m 90% sure would reduce their missed detections by about a tenth, but I didn’t get past the lobby. Didn’t get responses from emails on short notice and tried just dropping by without appointment. Techniques I developed for intel community can be used. I happened to be near Madison (from Virginia). Will probably try again when I’m out that way again in August. I probably ended up in a spam folder.
I wonder if key patents for EPA from algae could be acquired
Nice call. Looks like one more in a surprisingly long series of seemingly last chances to add relatively cheap. Run up to PDUFA seems likely to start before long.
Beautiful day on beach at Chincoteague, VA. Life is good.
Bogarde - I agree with and mostly follow the “don’t feed the animals” policy. If you are less than certain about the mineral oil issue, as I pointed out in my Seeking Alpha articles, the evidence against a major MO effect is quadruple overkill. The K-M curves are conclusive. Placebo harm raises the P curve, V benefit lowers the V curve. It’s visually obvious the risk reduction is from V bending the V curve down, not placebo harm raising the P curve.
The point about diminishing returns of statins means that reducing statins has not much effect unless almost all the statin is blocked, which defies common sense. The fist scrap of statin gives most of the benefit.
I don’t intend to enter into an exchange here.
If you’ve ever had a polyp (many people over 50 have, including my wife and me) you are no longer eligible for Cologuard, and are recommended for more frequent screening by colonoscopy.
AF opined on the possibility of an adcom. No surprise, he kept with his pattern of almost exclusively limiting his comment to those which are unfavorable to Amarin. (He suggests an adcom is still very much a possibility, which many people would consider an unresolved risk.)
AF's tweet yesterday:
Adam Feuerstein
@adamfeuerstein
·
13h
Replying to
@sentivcapital
@zbiotech
and
@Sports_bios
From my reading of rules, FDA must give $AMRN 60 calendar days notice for an advisory panel. The Vascepa PDUFA is Sept. 27, so that implies July 29 as the last possible notification date for a panel? Practically speaking, it would have to be well before that.
End of quote.
He was a day off on the PDUFA date. Is his remark about 60 days correct?His tweet was a reply to another tweet that included a statement of FDA policy that the FDA "intends" to convene adcoms at least 6 weeks before the PDUFA date, which would make the cutoff for informing Amarin a week or two ago. Of course, we know the FDA is not rigidly constrained by their intentions, goals, policies, or the law, but it seems very likely no adcom and it seems odd AF almost only comments about Amarin when there's something negative to say. Bizarre, since Vascepa is clearly the biggest advance in decades for the primary killer of humanity, and it's still an investment opportunity of historic proportions IMO as well.
Sincere question: does Stat have a reputation for intentionally fake news? Do we know if they can be paid to slant a story one way or the other? Their coverage of Amarin has been terrible and indefensible. AF and MH have both been given the facts about Vascepa and Amarin and they really don't seem to care about their false reporting.
I don't think there's anything to fear if there were an adcom, but not everyone sees it that way.
eboomer - Nice post, I agree. There are lots of reasons to sell an investment, whether it's B Bros or an insider. A sale is not as good an indicator as buying or holding. The only reason to buy or hold is confidence it will go up. The doubts are being squeezed out, MO is long gone for anyone a little bit smart and informed.
BTW, as discussed before, Matinas is nothing for Amarin longs to worry about. No one who claims otherwise should be taken seriously.
A quick glance at the Matinas website shows the crown jewel of their scientific achievement is a poster from about 2015 about a tiny (less than 30 days, less than 50 subjects), unpublished, un-blinded trial of Mat9001 (a blend of omega-3s including EPA and DPA) compared to Vascepa. They compare the increases of plasma EPA, and, as Adam Feuerstein noted in a Stat article a few months ago, their results for Vascepa were significantly different (worse) from confirmed data from much larger, published, FDA-reviewed Vascepa trials. Matinas' patent portfolio is also unimpressive. They discontinued work on Mat9001 for years until dusting it off after RI.
It seems quite clear Matinas is trying to coat tail RI and license their tech or just boost their share price. Any FDA approval for CVD would require a major outcomes trial (9 figures cost and probably at least 8 years before approval in the unlikely event anyone undertakes it and it succeeds). V goes generic in Aug 2029. The market doesn't seem to be falling for it much, share price is quite low after a brief modest bump up following RI, pretty much evaporated now. They recently hired some scientific advisors with impressive credentials, but that doesn't change the facts and their dim prospects.
Looks like there is, or soon will be, a big incentive to find a commercial means of converting DHA to EPA. Wonder if that will end up being feasible.
A conference call a while back (Q4 call maybe?)
UHC covered V for me off label $3/month co-pay 2 or 3 years ago before we switched insurers. Not on statin, trigs not high. Zero resistance, approved effortlessly.
MRC - Quote: "they [Amarin] have been desperately trying to negotiate a licensing deal for the EU territories, and have guided as much."
I recall JT being so desperate that he said he wasn't letting suitors for EU distract technical staff by asking them questions.
Quote: "there is a loophole that will cause them [Amarin] to lose the entire market to multiple generics producers within 3 years."
If you really know that, you're the only ones and you could leverage that info to make an awful lot more money than you could possibly make by selling your report. Why are you telling us for free? It seems like even you don't believe that info or you wouldn't give it away for nothing.
I submitted an edit with a photo of a real Vascepa capsule. I had used one of the stock pics they offered. Hopefully they accept the edit and do it soon. Thanks for the enthusiasm.
I’ve had good luck ($3/mo off label) with Aetna, and United Health Care a couple years ago. If at risk, it’s worth changing insurance for.
Thanks to all who had kind words about my SA article.
Thanks for posting. You noticed my AMRN rebuttal article went live before I did.
Already got about 800 views. I might have heard somewhere that the first 1,000 get a new car. On the other hand, I might not. I get about a penny per view.
Oh joy, Sharma showed up in the comments. Still waiting for MRC.
Possible slogan: Vascepa - for life.
Double entendre, take it the rest of your life to extend your life.
The new communications VP could probably help with some coaching, if he'd let her. My wife is in the business, and routinely coached execs before they gave interviews or made presentations. She had some remarkable success helping people (getting them to lose the notes, etc.) Wouldn't be hard to double JT's effectiveness at communicating. Don't want to overdo it, lack of slickness is an asset to a point, but he could definitely benefit from some smoothing up. Vascepa is the real thing. (Too bad that slogan is already taken.)
raf - I'll take that as a compliment. Been brushing up against him on Twitter and comment section of his SA article. BTW, be on the lookout for my SA rebuttal to his article, should go live any minute. I held back. He (or they) are anonymous, but we have their address (suite 4081 of a 3 story building where Allstate is in suite 205). Mail service only, at most. I thought of posting photos of their building and of Harvard Med School, as he anonymously indirectly impugned several Harvard Med profs who like Vascepa. I also held back on some of the science. Not much point in going past triple overkill.
Pseudo-science is one of my biggest pet peeves. Misusing expertise to fool the public is unethical in my book. Knowing a little science and throwing around some jargon isn't the same as good science. There was some skill, but applied to concocting bear arguments, not finding the truth. The truth is not on their side.
You haven't refuted my argument, here or anywhere else. Not even close.
The K-M curves are not tea leaves. They are a standard tool of trial analysis because they concisely present the trial data. 8,000+ subjects followed for ~5 years, extremely low p, SPA that precludes p-hacking, double blind, 450+ different independent facilities around the world, K-M curves summarize a great deal of valuable, highly reliable data.
As I pointed out to you on twitter, it's obvious that the placebo (P) and Vascepa (V) curves coincide initially (just slight routine statistical variation and apparently slight immediate blood thinning benefit from V, as expected). If MO had the immediate and large deadly effect you claim, in the initial period before most of the V benefit had had time to influence event rates, the P curve would have to start out high above the V curve. It didn't. The V curve initially starts out quite near the true untreated event rate, the same as a perfect placebo, except for the slight immediate blood thinning benefit. The P curve ended up virtually exactly in line with its initial rate, which was confirmed by the initial V rate. You can completely ignore the P curve and the V curve clearly shows wonderful risk reduction kicking in after about a year, compared to either the P curve or the initial V curve.
The V curve alone proves great risk reduction, without MO. You have nowhere to go with this. A lot of people understand it. You embarrass yourself. The curves are conclusive, there's no way around it, that's why the expert consensus agrees with me that Vascepa is a wonderful breakthrough. No one credible comes close to sharing your view. Your report is embarrassingly biased and flawed. The authors were wise to stay anonymous.
MRC - Nothing you say, here or in your 226 pages or anywhere else, changes the fact that, for the K-M curves, a harmful placebo like you suggest would raise the P curve, and V benefit lowers the V curve. From NEJM Nov 2018 Bhatt et al, the placebo curve ended almost exactly aligned with the initial P rate. No raised P curve means no significant harm by placebo. V curve strongly bent down after a year or so, with no help from MO, so the benefit is from V, not MO. You can't talk your way out of that. Stop embarrassing yourself.
tweet with RI K-M curves
Not that I’m defending the Adcom, but IIRC that particular moronic remark was by a non-voting consumer advocate.
I honestly don’t know the answer to your question or mine, was hoping someone would chime in with an answer.
DitD - Any precedent for FDA delaying or denying approval for a drug because the demand increased too rapidly for the supply to keep up?
AF acknowledged receipt from me of info correcting errors and crucial omissions in his very influential November reporting (including the peer-reviewed scientific literature references provided on the Amarin FAQ page etc.). I tried hard to be diplomatic. AF seemed to have no interest in correcting or discussing his errors, or being even minimally polite.
AF had less negative spin and his errors seemed more plausibly unintentional than MH. I've seen AF write good articles, but I'll never really trust him again after his refusal to set the record straight after the facts became clear. He seems to prefer to comment on Amarin primarily to bring attention to negative news. He doesn't say V is bad, but he greatly downplays its value.
I try not to focus too much on the past, but as far as I can tell, what probably happened in November is that Amarin was highly focused on the SNDA and declined to provide MH and AF access to their experts when they were writing their articles prior to the AHA presentation. (That was bad media relations by Amarin. Amarin management mentioned withholding expert access from potential suiters for a European deal at around that time, and MH told me Amarin declined to give him access.)
I think Amarin thought their story was very important (it was), and the details presented the evening of Saturday Nov 10 (details about MO and MOA etc.) would be reported. Neither AF nor MH reported on that, or apparently looked at other references (about MOA etc) on the Amarin website or apparently asked their experts to review any of that before opining. So, obvious, easily refuted misinformation about MO and MOA etc., was injected into the media and widely disseminated, and continues to echo. It's hard to unring that bell.
The Matinas trial was tiny and unblinded, and their results for Vascepa, which their trial compared against head to head for plasma EPA level, were substantially inconsistent with the Marine, Anchor and RI trials (much lower EPA levels for V than were observed in the better, larger, independent and published trials). Matinas also did not follow Vascepa label instructions their trial. Multiple big red flags, as I've commented before. Also patent issues and they'd need at least 8-10 years and a huge bucket of cash to complete a CVD outcome trial, in the unlikely event they attempt one. Their share price not lighting the world on fire, despite an increase coat-tailing RI.
Interesting Matinas says Kastelein called them and wanted in, apparently BEFORE he co-authored the NEJM editorial that mentioned MO doubts, and cast more doubt through uptodate.com.
OT - Came across this video of Deepak Bhatt playing drums with the legendary Steve Smith (drummer for Journey and many other prominent artists. Disclosure: it's a Deepak Bhatt, not the Deepak Bhatt.)
Bhatt and Smith drumming
It is important to take Vascepa with some fat. If you take it on an empty stomach, the amount absorbed may be reduced substantially (up to a factor of 13 if I recall correctly). I believe the triglyceride form of EPA (omegavia EPA only etc) can be absorbed without fat. I believe EPA has a half life in the blood of about 3 or 4 days, so doesn't seem like it should be a big problem to take the daily dose at one time.