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That was an impressive slam dunk, but I like this one:
slam dunk with elephants
With a SPA and endpoints met, I believe approval rate is more like 98%, and I believe V odds are more like 99% or more.
Good points. That most recent Bhatt video pointed out that there were RI subjects with trigs as low as 81, and the lowest tertile had strong RRR, very similar to the middle tertile, clearly indicating strong benefit unrelated to trig lowering and independent of trig level. The case for V for patients at risk independent of trig level is very strong, and I hope and expect future papers will make that even clearer.
I didn’t pay for the Nature paper, just followed a link posted by cardiologist Ethan Weiss on Twitter. Often new papers are free for a while before being paywalls.
Interesting new paper in Nature: "Oxidized phospholipids as a unifying
theory for lipoprotein(a) and cardiovascular disease." Way over my head medically.
Nature paper
On a road trip with limited access to news. Are they making any progress controlling the fire? There are helicopters that can drop water (I saw one in action in Bodrum, Turkey years ago.) Are the 400 firefighters making any progress?
I can see how people could expect Amarin’s share price to languish under $20 until after label expansion and perhaps a bit of the resultant sales ramp-up (or BO for the BOBs) around early 2020.
That’s because conventional wisdom says a big price change requires a big catalyst, which is usually true. But the usual rules don’t work well in unusual situations, and Amarin is very far from ordinary. I’m not alone here in thinking it’s crazy stupid undervalued here, and a potential catalyst not marked on the calendar is that at any time enough potential Amarin stock buyers could recognize the opportunity to push the price up. I also believe there is potential for better than expected sales pre-approval.
Prudent not to count on too much too soon, but I’d be surprised not to see higher prices before very long. Of course, I’ve been caught by surprise before, including by the current price weakness.
raf - I noticed you have 48,976 twice in a row. Is that a typo, or just a coincidence?
raf - Here's a plot of what you posted.
And here's that chart from Cantor-F a while back while we're at it:
I've been thinking about what we should be expecting for the intermediate-term trend for TRX (smoothed over ~3 or 4 weeks). I'd very much expect sales to be accelerating at this point, not just a linear slope of TRX vs time but bending upward. There is random variation, so it’s not realistic to expect ATH every week.
I’d expect that as a wave of doctors starts prescribing, they would write a lot of scripts for a while as they see their patients and switch them over. Once they’ve seen most of their patents and switched over those they feel are appropriate, their new prescription rate should slow substantially to just new patients. While a lot of healthier people have annual or semi-annual checkups, cardio said a lot of his higher risk patients (prime candidates for V) come in every few months, so I’ll arbitrarily pick an average period of 4ish months of high initial prescribing rate for a doctor to switch over most of their patients.
I figure the first wave of docs started prescribing after topline, a relatively small initial wave. I think a bigger wave came on board after mid November, another wave around January (sales force in place and starting to hand out NEJM hard copies etc), and call it another wave around late March (ADA, Cardiology Today article and ad, and other marketing and word of mouth). We’d expect sales to accelerate at least as long as more doctors are starting to prescribe than are completing their switch over of their patient base. Based on these assumptions, in February and March I’d expect acceleration that does not appear on the graphs. We know estimates like Symphony’s have difficulty catching inflection points (abrupt accelerations), and that is made worse by their recent problems if they resort to linear extrapolation, which is likely. So, my best guess is that when more accurate data becomes available, from Symphony or Amarin, it will very probably reflect higher sales and an increasing rate of sales, particularly for March.
I don’t feel I have precise enough data for a reliable computer model, and it's best not to over-fixate on this, so I keep it more qualitative than quantitative for now. The far bigger move will be after label expansion. My cardiologist has been enthusiastically prescribing since not long after AHA in November, and said others in his practice were too. I think he’s pretty typical of those who are aware of RI, and it seems like that's got to translate into sharply growing numbers sooner rather than later.
All that said, I do recommend patience and not over-watching our pot. It will boil eventually. It can’t not.
conclusions section from late November SA article about patents:
"III) Conclusions
In summary, there are 24 issued U.S. patents that cover Vascepa® according to Amarin based on its Vascepa® Orange Book submissions. These patents include both formulation patents and method of use patents. Of particular note are the 2 formulation patents, with expiration dates without extension, of 1/27/20 and 2/9/30 respectively. Furthermore, of the 22 Vascepa® Patents with method claims, two of these appear relevant in view of the Reduce-It trial and likely soon-to-be filed sNDA based on Reduce-It trial results.
Independent claims of these patents recite that a subject is on statin therapy, but do NOT recite that subjects have a triglyceride level of 500 or more. These two patents expire on 4/29/30 according to Amarin. Amarin has pending patent applications in the U.S. in the patent families that include the current Vascepa® Patents from which it might obtain additional patents that cover Vascepa® or its use or manufacture.
From an investor standpoint, it's good to know that there are issued formulation patents and method of use U.S. patents that Amarin asserts cover Vascepa®, and that most of these patents do not expire until 2030. It is noteworthy that we could NOT find support that the formulation patents were asserted in the pending ANDA litigations, although our search of the litigation record was not exhaustive.
As is the case with any issued U.S. patent, whether the patents are valid could be challenged in court or in the United States Patent and Trademark Office, and whether such patents actually cover the approved product, and potentially even whether the expiration date of the patents is correctly listed in the Orange Book could be challenged in court. Furthermore, the issuance of a patent that covers a drug does not provide freedom to operate for the drug. That is a separate legal analysis.
This document is for information only and is not investment or legal advice. Please confirm the accuracy of all information for yourself as none of this information is warranted as accurate "
Just came across a thorough review paper on lipid lowering agents. Mentions Vascepa just briefly a couple times, positive but appears to have been added as an afterthought. Published in Jan, so probably mostly written by Nov 10. Focus is mostly from a genetic (Mendelian) point of view. Sorry if already posted, hard to keep track these days.
lipid paper
And Mick Jagger opted to come to the US for his heart surgery.
MTNB hired a top notch science advisory committee, but the old trial results they've been waving around, claiming much higher EPA levels than V, are pure BS and inconsistent with real trial results including Marine, Anchor, and RI. They have DPA, so I don't see how they get to bypass the outcomes trial, so even in the unlikely event that they prove efficacy and bypass patent barriers, it will be many years before they could possibly compete for the CVD market. It seems to me like a ploy to bump up share price.
Re scripts - Keep in mind fluctuation is normal, and every week can't be expected to be an increase, even in a strong acceleration such as we are having now. Remember this graph someone posted a little while back, from Cantor-F:
If updated, V TRX would literally be off the chart.
Also, what matters is how many doctors start prescribing. Each doctor, once convinced, will take at least several months before seeing all their patients and putting them on V, so there will be a lag of months before seeing all the benefit of marketing efforts. There is more delayed benefit as they convince fellow doctors in their practice. Patience. Things are going well. At some point the market will recognize Amarin’s value.
Amarin played by the rules. There was always going to be an RI outcomes trial, and it was well under way before the adcom. Panelists said they felt bad voting no because Amarin had done everything asked of them. They had to vote no because FDA moved the goalpost. The only appeal option was to FDA. Amarin has nothing to be ashamed of IMO. I read the adcom transcript several times, it was remarkable. But, let's try to look forward. The future looks bright.
I believe the Anchor label said it was for use by people with CVD risk factors but it did not claim to reduce risk of CVD. It just claimed to reduce trigs, which it did. I believe the FDA had agreed to that language in the Anchor SPA, and they easily could have changed it if that had been the problem. The argument was made that there was not really any other reason to lower trigs in the Anchor population other than CVD risk reduction, which is true AFAIK.
Don't see a lot of reason to keep on about this, but it is good for new people to know what happened before, so they know what to expect from FDA now. I don't expect major FDA problems going forward, because the circumstances of 2013 are not in pace now. FDA has no incentive to stop V, which is an absolute no-brainer at this point.
BTW, not trying to be contentious, the standard by which to approve a drug is a topic about which reasonable people can and do disagree, but at the 2013 adcom the point was raised by a panelist that the approval of V and Lovaza for trigs>500 for pancreatitis risk reduction was not based on an outcome trial. It was just based on trigs as an accepted risk factor. It would be absurd, he said, to consider a trial letting a bunch of people with super high trigs go untreated just to see how many got pancreatitis.
That same panelist pointed out statins were allowed to be sold for years during their outcomes trial. If they hadn't been (as they wouldn't have been allowed under current policy), it's not clear anyone would have undertaken the tremendously expensive trial. And, that policy, if announced years earlier, may very well have stopped Amarin from giving it a try. Maybe V would just be a dry eye cure now, or not marketed at all. (I believe Marine was just a stepping stone to Anchor/RI.) We will probably never know how many small companies (or large) aborted a promising project after seeing what happened to Amarin.
There was pretty good circumstantial evidence for V in 2013 (JELIS, genetic studies indicating the trig/CVD correlation was causal, etc). It's a shame there wasn't a panel discussion to consider whether it was in patients' interest to give their doctors the choce whether to try V a few years earlier IMO. Again, reasonable people can disagree, but I believe in more choices for doctors and patients, not less, as long as the drug is safe and there's a reasonable case for efficacy and all relevant info is made readily available during a post-approval outcomes trial. This is primarily an issue for CVD, because the trials take so long and cost so much (hundreds of millions).
The Mason video may be more accessible than the paper:
Mason video
LB - You recall correctly, the voting question was carefully written to be ambiguous. It was only made public a couple business days before the meeting. A panelist asked for clarification of the vague question before the discussion, so they could understand what it was they were supposed to discuss. The chairman delayed explaining that until immediately before the vote, and it was explained that FDA wanted the question to be interpreted to be whether V had been proven to reduce CVD risk, instead of whether it reduced trigs, which is what the label was going to say and which is what the Anchor trial had been designed to prove, and which had been proved.
Quote: "If they only asked for lower triglycerides label without any label claiming CV benefits, they should have gotten it"
That is all they asked for. There was actually quite strong evidence for CV benefit (JELIS, lower CVD risk in fish-eating populations, evidence that AA/EPA ratio was a strong causative risk factor, genetic studies, etc), but FDA chose not to have an informed debate about that or allow Amarin to fully present the case. It was quite ugly. Most of us who lived through it have tried to put it behind us, but it does explain Bio Bill's intensity IMO.
To add insult to injury, IIRC the failed niacin/fibrates drugs remained on the market with unreduced labels for over a year, and I recall a new variety of fibrate being approved by the FDA the same week Amarin's SPA was rescinded. At least V hadn't been proved to not work, was very safe, and the niacin/fibrates crowd badly needed new options.
Prior to 2013 the FDA had allowed CV protective drugs, including statins, to be marketed after trials that proved safety and efficacy for improving a generally accepted CV risk factor, such as LDL-C, HDL, or trigs. CV outcome trials, which often take over five years, were performed after FDA approval, which allowed more choices sooner for patients and helped finance the super expensive ($100M+) outcome trials.
Consistent with that, the FDA had a SPA (special protocol assessment) agreement with Amarin that after the Anchor trial demonstrated safety and efficacy for reducing trigs, V could be marketed for patients with moderately high trigs, labeled for reduction of trigs, subject to having an outcomes trial (RI) underway and at least 50% enrolled. Amarin met all those requirements, and prepared for label expansion. Amarin hired hundreds of new sales reps, made substantial financial commitments to greatly increase supply, and planned their finances around having the label expansion FDA had promised.
But, after some other post-approval outcomes trials failed (niacin/fibrates), FDA decided to change policy and require outcomes trials first. Amarin happened to be the next in line when that change came. FDA decided to not tell Amarin about the policy change until literally the last possible moment, at their adcom (advisory committee) meeting shortly before expected approval of label expansion. At the adcom, FDA didn't even tell the panel or Amarin until moments before the vote, after Amarin had presented their case and discussion was virtually entirely complete.
FDA has a long history of moving the goalpost in the middle of the game, and congress passed very clear laws requiring that they give notice, and those laws were flagrantly violated, badly hurting Amarin and many of us who were investors at that time. Amarin hired a sales force and let most of them go just weeks later, paying millions for severance packages, and the stock price quickly went from the upper teens to around $2 or $3, eventually bottoming out well under $1.
Nice to hear Sharma deleted those anti-Bhatt tweets and presumably will think twice before doing that again. A few of us tweeted back at him, and explained why he was embarrassing himself.
sts - Preston Mason has several published papers. One of the recent ones:
Mason paper Jan 2019
I don’t know what peak V sales will be, but I believe they will be shockingly high, before terribly long. Already sharply accelerating, the big move will be after label expansion IMO, which I expect to be expedited. Three digits within 3 years.
NNT is number needed to treat (to prevent one event). Smaller is better. It is defined for a particular population for a particular time frame, so appropriate adjustments should be made before comparing. It is the multiplicative inverse of absolute risk reduction (ARR) expressed as a probability (not as a percent). ARR is 4.8% for RI, so NNT is 1/0.048 = 21 (for primary MACE events only). NNT is much better for total events analysis, when all events are considered, not just the first event for each subject.
Bhatt is not paid directly by Amarin, AFAIK, and gets same money whether V does well or not. Plus, he has a spotless reputation.
Vascepa has all kinds of side effects: Dry eye syndrome alleviation, possibly helps with cancer, any disease ending in "itis", and a bunch of other stuff I'm too lazy to list. Not rigorously proven yet, but neither is A-fib or arthralgia (which was on the Marine label but apparently not observed in RI). Not to mention weight loss, mood improvement, and the junk thing.
He knows better now.
AVI - It certainly would be in their interest to extend STRENGTH. The RI startup period was around 1 to 1.5 years. If STRENGTH is 3 years, and RI was 4.9, subtracting a 1 year startup period essentially changes the effective trial lengths to 2 and 3.9, so RI has an advantage factor of 3.9/2 = about 2. When comparing NNT, there would be an adjustment by a factor of 4.9/3 = 1.6, so Epanova handicapped by about 1/3 without even considering the disadvantages of the DHA content. DHA may help a bit for the trig part, but the trig part is fairly small. Reasonable guess is STRENGTH shows underperformance by a factor of about 0.6 or worse (for them). They focus on hi trig lo HDL subgroup, for which V got 38% RRR, so STRENGTH could maybe show RRR of ~0.6 x 38% = 23% or less. Maybe call it 20ish percent RRR. Not much more than half the V RRR for that subgroup. Not clear that gets them to market, even ignoring the patent issue.
I do expect benefit, despite the DHA, since fish eating populations have less CVD, and they get the DHA too, and some other undesirable stuff.
I'm not sure what Dr. Nissen meant by the jazz hands when he said about a year to go on STRENGTH. May be just hard to know when events will accrue. Seems like it would be a major change to extend in mid-stream, and pre-specified is preferred. I assume there might be a statistical penalty for such a change. It would probably be worth it. There's no possible scenario I see where Amarin is hurt much.
MrM - I agree with others that the FDA in 2013 responded to circumstances at that time (failed post-approval trials for fibrates and niacin) that gave them incentive to do what they did. It had nothing to do with any grudge.
Circumstances now set up completely different incentives for them. No incentive to torpedo V, and huge incentive to approve quickly. To me the primary question is not whether they approve, but how flexible they are about expanding the label beyond RI inclusion criteria. Good chance they are inflexible, but that doesn't matter much, since any conceivable label will cover tons of people, and lots of docs will prescribe off-label as mine have for years. (I've always had a $3/month co-pay off-label without being diabetic or on statin or having CVD or very high trigs, through two different major insurance companies with zero resistance.)
Regarding adcom panelists with conflicts: I can't think of a possible conflict that would give them incentive to not approve or to want to reduce the scope of the label. STRENGTH folks (Nissen, Kastelwin or others) will also want approval with broad labels, as a precedent for their drug. Big pharma may hope to snap Amarin up cheap (although it's pretty clear now the ship sailed on that long ago), and may benefit from battering Amarin to increase their desperation, but they would not want to damage the jewel (expanded approval) they covet. Ditto for the MTNB folks (they hired several impressive KOLs for their advisory board, including Ballantyne and Kastelein, but they're still pedaling a highly dubious unproven drug at best, with a very long, tough, and uncertain road ahead).
Life is full of things to worry about, but I don't worry a whole lot about adcom or FDA approval. Both will be absolute no-brainers IMO.
I believe the main thing holding back Amarin share price is not FDA or science or earnings projections but simply the market's inertia. The price is stupid cheap for several reasons, too stupid to last very long IMO. We don't need more catalysts to move price, the AHA results are not yet anywhere near fully priced in, not to mention ACC. ADA is another brick in the wall that will help dissipate the fog.
Something's coming. Inexorably. It won't be overnight, but it won't take years IMO. I expect a great 2019 for AMRN longs. Like owning Amazon stock under $200 back in the day, except I expect Amarin stock to move up much faster and further in the long run.
If this is a cult, it's a good one. I don't think most misguided stock
cults have this many highly qualified and informed members, who are aware of cults and checked for the warning signs. My only other "Cult" stock was EXAS, and my biggest error there was selling too much too soon. (EXAS sales at 10x, 20x, and 30x seemed like triumphs, but it went to over 100x over a period of years. Some on this board remember the days of talking about getting to $50 or more when it was around a dollar or two. It recently approached $100. I still have a few shares.)
GLTA
QUOTE: "It's not that big of a deal … only ... 30 million people with diabetes in the US."
Yeah, at roughly $25 in share price supported per million scripts, that's only $750 per share for one subgroup in one country.
It's the whole market (S&P too)
JL OT - Bernini was a bit of a live wire. Many creative people are. The rival reportedly had carved ass ears pointed at Bernini's place. The rival ended up committing suicide and the church wouldn't let him be entombed in the fancy place that had been planned for him. They only carved his name where he ended up, but if they had carved anything else, maybe this lesson would have been fitting:
Two rules:
1. Don't sweat the small stuff and
2. It's all small stuff.
Not sure why he did it, he was very successful (like your namesake). Sometimes people just get their wires crossed.
Quote: "I am a plant"
rhododendron?
Thanks JL. I think Amarin is marketing well now. I liked their approach of paying cardiologists to take a survey, which I assume conveys basic information about V, and the Cardiology Today article with advertising is a smart way to spread the word. I would expect a noticeable uptick from that article alone, and there are other similar efforts.
I heard Bernini carved a male genital on his house pointing toward the workshop of a rival. It was later removed for the sake of decency. If someone had it today, I wonder what it would bring on eBay. I'd bid on it, as a conversation piece.
JL - Quote: “.Events like Vascepa in medicine come along once every 70 or 80 years... Amarin has that [Amazon] kind of potential”
Couldn’t agree more that the situation is unique and historic from both medical and investment points of view.
The RRR and NNT numbers speak for themselves regarding the historic medical benefit, even without considering other likely indications.
The current share price is crazy low relative to valuation, even after the recent rise from $3ish to near $20, based on the huge market and near complete lack of competition or other likely obstacles to serving that market. IMO, the current low price is the result of an unfortunate series of events and is too irrational to last very long.
Biotech claims of breakthroughs are common, and almost all are exaggerated or fictional. So, skepticism is natural. Amarin management did not seem media-savvy in November, when they were slow to effectively address concerns about MO and MOA. They were, understandably, highy focused on the SNDA, and apparently declined to provide a spokesman (besides Bhatt). I wish they’d given MH a brief phone interview with an expert. Amarin was under-represented and MH took a negative stance. Amarin may have thought their evening presentation sufficed, but it was too late and not covered by Forbes or Stat. MH told me when Amarin didn’t provide a spokesman, it wasn’t his job to look on the Amarin site for info.
So, easily refutable misinformation continues to circulate. The recent Cardiology Today cover story, and ACC publicity, should help. I expect sales to further accelerate in the coming months.
FFS - No problem. BTW, I think most likely there will be an adcom, not because of worries about MO or MOA, but because it's a novel treatment for a huge market. I also expect the topic of MO to be raised there. But, the facts are too clear for it to actually be considered an issue of any real substance. If someone's looking for a list of things to complain about, it's one of the few possibilities, along with AF and bleeding. The downsides are quite tiny compared to the benefits.
Dukesking - No guarantee re the discount program continuing, but that's my opinion.
dukesking - The discount program has always been temporary for a year at a time, and has always been extended. They also limit each person to 3 years, if I recall correctly, but you can appeal for an extension, as I did. My extension was immediately granted a year or two ago. I assume the only reason they would end the discount program would be if sales were strong without it. It seems to me if they wanted more revenue, a modest price increase would make more sense than eliminating the discount card. Amarin management is smart, so I expect the discount program to continue. The market of people with elevated risk and good insurance is large and seems like low hanging fruit to me. The best way to pick it is keep the discount, and that's what I expect at least for the near term.
FFS - There is no MO or MOA mystery for anyone who has spent half an hour to look into the facts. Neither AF nor MH, nor some of their experts, did that (at least in time for the Forbes and Stat articles), but the FDA had thoroughly looked at it years ago. With p<0.00000001 and a rigorously designed trial, V is not a one-off unicorn. The FDA goes to great lengths to avoid embarrassment to themselves, and the path of greatest embarrassment would be to further delay V and further continue the obvious preventable carnage.
My strength is more science than stock market prediction. I tend to mostly agree with JL that Amarin is unlikely to settle for less than a very high BO price, because they don't have to and they appreciate the value they have. BP likes to buy at a deep discount, with risk thoroughly eliminated. They often can, because it's such a long, draining battle to get a drug approved, fledgling bio-techs are often desperate. So, there's a good chance BO doesn't happen IMO. Management is patient, and knows this is not a quick flip it and move on situation. The middle path of GIA in US and some kind of deal ex-US seems likely, but I don't spend a lot of time studying that.
For those who think BO is the only catalyst that could move the stock much now (SNDA too expected to be a huge catalyst IMO), I submit that the market has yet to properly digest RI results, and spreading realization of that could move AMRN. Hard to know, AMRN remains stupid cheap IMO, and stupidity can have surprising resistance to clear facts. I think the recent publicity in Cardiology Today and similar publicity/advertising to come will increasingly move sales and stock price over coming months. we'll see. It's more a matter of when, not if, IMO.