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Retinadoc
Excellent suggestion!
That data would be very useful.
The R-it Smoking study may say: no matter what your smoking history is, you will benefit from V but it could also be interpreted as: no matter what your smoking history is, if you take MO your CVD risk goes up 20 plus %.
Comparing V smoker to V non smokers would be helpful information.
Capt
Correct me if I’m wrong but aren’t they looking at using 4gms of MND-2119 and thus 4 x 1 gm V2?
“In this multicenter, 12-week, double-blind study, patients with high triglyceride (TG levels between ≥ 150 and < 500 mg/dL) undergoing lifestyle modification were randomized to MND-2119 2 g/day (n=145), MND-2119 4 g/day (n=145), EPA-E 1.8 g/day (n=145) or EPA-E 2.7 g/day (n=145)”
JELIS used 1.8gm of EPA-E and the ROW had to use 4gms of V to get the same serum levels. The new MND-2119 will require the same higher dosing to achieve serum levels in the ROW (due to difference in baseline levels). They included a higher dose of 2.7gms of EPA-E in the study but that is dosing never seen in Japan before. That would be equal to 5-6gms of V in the ROW.
Correct me if I’m reading this wrong.
Kick
“Patient only takes 1 cap once a day”
V is pure IPE. 1 gm in a cap. V2 may be once daily but you will still need to take 4 gms which would be a massive capsule only swallowable buy a few porn stars. Pts will be taking 4 caps (same size, maybe even a little bigger than current V) once daily. Insurance companies won’t pay more so that the Pt has the convenience of once daily dosing.
V currently still has very poor insurance coverage after being on the market 10 years. V2 will have zero coverage for at least the first 3 years during which it has the FDA exclusivity protection.
BioInvestor3
Amarin got 3 years exclusivity for the new CVD indication using the R-IT clinical trial. What good was it?
Dogn
“So price V2 $1 less than V1”
That is the goal of the exclusivity agreements Amarin is pursuing with insurance companies currently. V2 doesn’t really change anything. Whether Amarin gets the insurance companies to agree to gV minus a few bucks for V or V2 doesn’t really matter.
Dogn
Great research but I would like to point out the primary obstacle: Insurance companies will simply refuse to cover Vascepa-2. Just like when physicians fill out a prior authorization specifying their patient needs to be on Vascepa DAW for cardiovascular risk reduction and the insurance companies reply they will only cover gV, if V2 is so much as $1 more expensive than gV they will simply refuse to cover it. Vascepa/statin faces the same fate. Until Amarin has a clear and decisive victory against HealthNet, including all avenues of appeal exhausted, insurance companies enjoy complete freedom to disregard patents.
I think we have all learned that it is not your doctor nor your pharmacist that decides which drug you get. The insurance companies, run by accountants/actuaries, are the ones who decide which drug is covered and therefore which drug you will get.
Dogn
“Ethical drug” is just a term used for a “brand drug” and an intentional dig at generic companies that don’t provide any intellectual advancements in the pharmaceutical industry.
Bioinvestor
Maybe they are looking at a combination of the 2 ideas, like the suggestion I sent them 8 months ago:
https://drive.google.com/file/d/1toZTExgyvbSXJpqti8Q4WPL6Wzwuunl4/view?usp=drivesdk
Zip/NS
HealthNet continues to this day to offer the generic to patients who have a PA for the cardiovascular indication. If the PA was the smoking gun that people think I am sure they would’ve changed their policy, but they have not.
“Insurance companies all know that they are infringing on Amarin's CVD patents when they fill the prescriptions for Vascepa with the generic version, but they do it anyway to save money for themselves by dispensing the generic version, which they pay less for.”
As I stated previously and if I remember correctly the HealthNet defence quoted caselaw that stated clearly that merely making product “A” less expensive and product “B” was not enough to be found guilty of induced infringement. If it was, it would essentially make it illegal for the generics to be less expensive than V. If V was $300 and the generics go to market at $275 then Amarin could argue they are inducing infringement by making gV less expensive, regardless if the indication is known or not.
NS I agree that your perception of the legal argument by Amarin makes logical sense. I also feel that healthNet is inducing infringement by making the generic less expensive to the patient. I for one have learned that logic and legal outcome have absolutely nothing to do with each other. The law is about finding a loophole and getting through it. Case law stating that merely making the product less expensive is not enough to be guilty of inducing infringement is what HealthNet is counting on to continue to give favourable pricing to the drug that costs them the least amount of money. The only difference with the PA is that everybody knows the indication. Should HealthNet not be allowed to offer gV if they know it is for CVD? It’s not HealthNet’s job to enforce the patents. If gV costs them less than V why do they have to charge more for gV just so they don’t induce their client to violate a patent that their client has no idea even exists?
HealthNet does not appear worried about the suite because if they were they would have changed their policies or their pricing or SOMETHING but instead they proceed exactly as before, they offer the least expensive product available at the lower price.
Even in the best case scenario we are looking at a minimum 3-5 years for this case to be resolved. This freedom to use the lowest cost product is far too important to the insurance industry to not fight to the bitter end and win at all costs.
Laurent
Great info, thanks for posting. Helps to partially explain the higher placebo event rate in R-IT as well, R-IT population was sicker than STRENGTH.
Orbapu
Absolutely correct!
NS
You have read more about the lawsuit than I have but IIRC, and I certainly could be wrong, the HealthNet original defence document stated case law that merely making a product less expensive than another is not enough to be found guilty of inducing infringement. There has to be some action taken like promoting the patented use for them to be guilty.
Gusman
Neither the pharmacy nor the insurance company is violating the patents if they offer the Pt Vascepa-R-IT at $300 and gV for $10. It is the Pt (in the eyes of the law) who is violating the patent and choosing gV because it costs them less. HealthNet’s entire defence is that it is not considered inducement if all you do is make product A less expensive than product B. It’s the person who buys the product who is responsible.
The only solution is exclusivity contracts like MK is negotiating now.
Ramfan60
Not so sure about the combo. Insurance will refuse to cover combo and suggest gV and gLipitor instead. If it’s a penny cheaper to use 2 separate generics then that is what the insurance companies will cover.
Bfost
It didn’t last. When Zyban Rx would get rejected as not covered the Pts suddenly were diagnosed as depressed and prescribed Wellbutrin. I haven’t seen Zyban around for several years. I’m sure Wellbutrin is still being prescribed for smoking cessation but almost all Wellbutrin scripts are long term now.
Gusman
A prior authorization filled out by the prescriber specifying CVD risk reduction is useless in preventing generic substitution so how could changing the name be any better. “A rose by any other name is still a rose”
Laurent
I sent you an email to clarify the event numbers. Let me know if I understood them correctly.
Thanks
Laurent
Great work! Thanks for sharing
JRoon71
I had a private video call with Dr Bhatt and asked that same thing. He said KP ran the trial because he approached them. Due to a lack of time and funds Dr Bhatt approached KP because they had the database necessary to do it quickly and cheap. KP received free V for their clients which saved them millions. I asked why they didn’t just look in their current database to see if there were signs of efficacy and he replied that there weren’t enough KP Pts on V because KP “doesn’t believe in preventative cardiology” unless it’s cheap like generic statins.
Skipperdog11/Capt
Bhatt said they submitted a more complete review to the editors but the editors decided to use only the parts that ended up in the review. His response was that they would have to publish the remaining data at a later date in a different publication. There is definitely some “politics” going on at the journal.
JRoon71
As for Canada
National pricing negotiations are complete and the confidential (as far as I know but HDG’s crystal ball can probably tell you) agreed upon reimbursement is set.
So far Quebec has started coverage BUT have put the TG requirement above 2.27 mmol WTF!!! Quebec ALWAYS has to be “distinct” (Rose will get that comment) in everything they do.
Ontario should be announcing any day now and I suspect it will more likely follow R-IT criteria and be secondary prevention only. There will be some degree of “restriction” where MD’s will have to fill out a form to ensure the Pt meets the criteria but it is not generally a form that denies approval. Doctor prescribes, fills out the form assuring government that the Pt meets the criteria and coverage is granted within 24-48 hours (rarely denied if the criteria are met).
New Brunswick also approved recently and Department of Indian Affairs approved which covers Native Americans/First Nations people anywhere in the country.
BC and Alberta should be coming later this summer
To clarify: government coverage in Canada means anyone on social assistance (welfare) or over the age of 65 will pay between 0-$10 for a prescription of up to 3 months supply. People with private insurance through work pay between 0-$84 per month and virtually all private plans cover it.
Drug reps generally do very little in July and August because nobody wants to attend educational functions during the summer. I suspect the promotional rollout to happen early Sept.
Dogn/Capt
Another Serhan paper
https://drive.google.com/file/d/1-sImM-pV_XlBf3jNgw4-1LmnAF20bEXb/view?usp=drivesdk
Dogn
Another good article on Resolvins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682745/pdf/nihms-1617799.pdf
Dogn
If you want to research SPM’s:
Here is a great article with the 2 most important researchers in the world: Dr Peter Libby (The father of cardiovascular disease as an inflammatory problem) and Dr Charles Serhan (world leader in SPM research).
https://drive.google.com/file/d/1x6Xo-fo96TRqD31whSosVvN4fKQW8eTj/view?usp=drivesdk
https://drive.google.com/file/d/1IMvrY1gjaW4JSvCFdmMwMRIqR-dnIWEa/view?usp=drivesdk
I contacted someone who is a real expert in the field and has a PhD in lipid biochemistry with my concerns about the biomarker study. Here is his response:
“First, IL-1B and IL-6 are upstream effectors of CRP, meaning that elevation of all markers did not necessarily mean that elevation of multiple markers of this pathway confers additive risk. The strong correlation coefficient between IL-6 and hs-CRP in both arms supports this conclusion. Previous analyses have shown that hsCRP variation in the placebo arm was minor on an absolute scale. The estimated hazard ratio per unit hs-CRP value suggests the ~0.65 mg/L (50%) difference in hs-CRP between arms from baseline would increase CV risk by < 0.3% in the placebo arm. It is also true for the group of patients treated with IPE, whereas the minor changes in biomarkers levels are unlikely to reduce the risk of CV event by 25%.
Specialized pro-resolving and other anti-inflammatory mediators, for example, are powerful anti-inflammatory molecules produced from EPA, and EPA can reduce the production of proinflammatory factors from arachidonic acid competitively. None of these, however, has been measured in REDUCE-IT.
The same phenomenon might apply to oxLDL and LP-PLA2, which usually increase with rising LDL levels.
Additionally, Lp(a) is genetically determined and associated with CVD in mendelian randomization studies. However, serum levels were in the normal range (< 30 mg/dL) at baseline and on treatment in both arms. The serums levels in both arms were definitely below any limits associated with increased risk of CV disease.”
I found this quite helpful at reducing my concerns about the biomarkers.
NS
Last quarter I calculated (roughly) that Amarin had 13 million bottles of V in inventory. At the current rate of selling 65,000/week that gives them 200 weeks supply. It will be a long time before Amarin needs to increase API purchases.
Laurent
Good points and appreciate the stats analysis. We may be waiting for MITIGATE data to strengthen RRR or p value.
Did we ever get clarification on the number of patients on V? Last time I checked clinical trials website still listed a 10 to 1 ratio so that would mean 36,000 comparators versus 3600 active patients on V to give the total pop of 39,600 (an odd number). But I don’t believe that was ever confirmed and someone (possibly Kiwi) implied it was still the original 1,500.
Capt
Great research as usual. Thanks for sharing.
Here are a couple points/ideas/concerns I have:
1) The MO issue in the past has been primarily about whether or not the mineral oil interfered with the absorption of the statin causing a reduced statin benefit leading to elevated LDL-c and corresponding increase in MACE. FDA, Health Canada, EMC, NICE focused almost exclusively on the reduced statin benefit. The issue here is purely about inflammation and that issue has not been resolved. 2-3 biomarkers of inflammation increasing in the MO arm would be "interesting" but not concerning. 7 out of 7 is concerning. IMO MO does not appear to be an inert placebo. I don't buy Nissen's original theory about reduce statin effect but the signs of pro-inflammatory effects are hard to ignore.
2) JELIS did show 19% RRR but their endpoints were primarily "soft" events like angina and not MI's or Strokes.
3) EVAPORATE did show a 19% reduction in plaque with changes in morphology to more stable forms of plaque BUT the MO arm showed a 109% INCREASE in plaque. That big of a change in 18 months made me question the accuracy of the measuring as well as the potential effects of the MO. I have not had a chance to look into the GARLIC5 trial and it's cellulose-based placebo other than the review you posted.
4) you can't use a "per dose" comparison between JELIS and R-it, it was based on baseline serum EPA levels and JELIS ended up with higher serum EPA levels. It's misleading.
5) (And this is the one that keeps me up at night) CANTOS. CANTOS trial showed that directly reducing inflammation with canakinumab, an interleukin (IL)-1ß neutralizing monoclonal antibody resulted in a 15% RRR in MACE. hsCRP was reduced by 26–41% in a dose-dependent manner (150mg or 300mg) and median IL-6 was reduced by 19–38%. In R-it hsCRP was increased by 39% and IL-6 was increased by 20% in the MO arm which had a 25% difference in MACE. I realize and agree that the absolute changes in these biomarkers are small but the percentage and P values are significant.
Let me be clear, I am NOT saying MO caused a 25% increase in MACE and that V provided no benefit. I am saying that to disregard these biomarker changes is like putting your head in the sand.
CARDIOLINK-9 provided stat sig reductions in hsCRP, d-dimer and pt symptoms of COVID with no MO being involved. PREPARE-IT provided positive trending data (p=.18) of hospitalizations for COVID and p=.06 for FLU-PRO score pt symptoms so I certainly believe V has a positive effect on inflammation and disease progression.
MITIGATE and RESPECT will provide some critically important data but it is a 2 sided sword as another poster mentioned. I'm still optimistic about both these trials but admittedly a bit less optimistic than I was 10 days ago. Keep in mind R-it included primary prevention pts who only had a 19% RRR so they diluted the final RRR. Both these trials involve sicker pts, all secondary prevention.
Unless Amarin can convince Kaiser to let out some data early, we are IMHO confined to a weak stock price and uncertainty until AHA in November. If nothing else, Amarin has a much harder road ahead when it comes to price negotiations with this new data fueling the fire.
Keep up the great research, you made some important positive points. I just felt the need to be the devil's advocate for a fuller perspective.
A positive view of Biotech in the second half of 2022
"Big pharma, their balance sheets are pristine. They have tons of cash on hand, and I think you're going to see in the second half of the year biotech outperform, led by some M&A from some of the big pharma," says @jfahmy. pic.twitter.com/uNwsL1CjVD
— Worldwide Exchange (@CNBCWEX) July 1, 2022
Laurent
I agree that Inclisiron provides no added benefit to other PCSK9’s, it’s just more convenient for the Pt. It’s going to be a hard sell to get most payers to agree to cover.
IPE is a completely different situation. I haven’t read the document you provided on how they came to the conclusion there was no added benefit but I assure you that decision was based solely on finances and not on science.
NICE dragged Amarin through 3 rounds of public debate and even brought in Steve to try and pressure Amarin to drop their cost. If Germany can’t offer more than $45/month I am sure Amarin will walk away. This has to be a pressure tactic, but like I said I haven’t read the document. IPE is part of the treatment guidelines(several), they don’t do that if there is no proven benefit. Let’s see what happens.
momoney
This is not about playing the next move perfectly. This is about the current SP being $1.85 in 2022 with amazing R-IT results, EU approval and a great reimbursement rate in the UK. I never would have imagined Amarin at $1.85 at this point in time given my belief that V is a life saving, practice changing completely new therapy that should be flying off the shelves. But it’s not. It’s not “selling itself” like one former board poster predicted. What does this mean? It means I was wrong. Very wrong. And if I am to develop an accurate view of Amarin’s future I need to start listening to people who don’t see the future through the rose coloured glasses I have been wearing. WS has a completely different view of Amarin’s future and I want to understand that view to adjust my expectations and adjust my investment strategy.
My opinions/views/expectations are completely clouded by the positive scientific data. I need to appreciate the financial perspective and to do that I need to listen to people with different opinions/views/expectations. Someone with the balls to short this incredibly undervalued asset obviously has a different perspective than I do, so I want to hear it.
iwanderer
There are some that value your input. I, for one, appreciate the open and honest views of your short sales. I don’t learn much from someone who just agrees with my position but I can learn from someone who challenges my view and lays out a rational explanation why.
Keep posting
In case this hasn’t been posted yet, Dr Bhatt will be presenting at ESC on the R-IT trial focusing on MI’s.
REDUCE-IT: Significant Reduction In ST-Elevation MI With Icosapent Ethyl.
Speaker: Deepak Bhatt (Harvard Medical School - Boston, United States of America) DLBhattMD
Time: 08:18
https://esc365.escardio.org/esc-congress/sessions/5580-latest-science-in-primary-and-secondary-prevention-and-environmental-health
There is also the R-IT smokers presentation and a cost benefit analysis of V in the UK
Capt
“Highlights
•
MND-2119 is a self-emulsifying eicosapentaenoic acid ethyl ester.
•
MND-2119 was tested in hypertriglyceridemia patients.
•
MND-2119 2 g/day was non-inferior to Epadel 1.8 g/day in lowering TG levels.
•
MND-2119 4 g/day was superior to MND-2119 2 g/day in lowering TG levels.
•
MND-2119 appeared safe and well tolerated.”
The dose would remain 4gm/day. 2 gm was non-inferior to 1.8G while 4g/day was superior to 2g/day.
ORBAPU
The only reason for the disclosure IMO was to publicly threaten Amarin with calling a new vote to remove people if Amarin doesn’t improve their relationship with Denner. I suspect this has less to do with Board representation and more to do with strategic planning and Amarin’s willingness to adapt Denner’s “advice”.
As for Denner’s involvement in general, I think it’s good news for those looking for a quicker but lower $ BO vs bad news for those who were willing to wait a little longer for EU market to develop and generate a higher BO as DOGN pointed out. For me it’s been 8 long years but I’m willing to go 2 more for a true or maximum return.
Note: if you look at XBI from Feb 2021 to now you will see a very similar decline to Amarin over the same period. A lot of the current SP situation is a sector problem and not just a management problem. When XBI rebounds I think we will see a similar rebound with Amarin regardless of who is running the show.
JRoon
It may have failed because serum EPA levels were too low. We don’t know for sure why it failed.
Rose
Yes, so far only Quebec has added V to their provincial formulary. Ontario should add it within a couple weeks. It is common for coverage to start at different times for each province and typically Quebec and Ontario are the first to add. BC will probably be next.
Capt
V is “approved” for diabetes and 1 additional risk factor (which almost every diabetic can qualify for) but reimbursement is only for Pts with “established cardiovascular disease“ which a large percentage will have but reimbursement is purely for secondary prevention.
$181/bottle is a major accomplishment considering how hard NICE fought.
Shadolane
Regardless of the effect on SP today (more likely influenced by inflation data’s effect on the overall market) the fact they got $181/bottle approved by UK is SIGNIFICANTLY more than they currently make per bottle in the US (roughly 33% more per bottle). That is a healthy boost to their margin and a very positive sign for the remaining ongoing negotiations.
Personally, I’m very impressed with these results. It shows the value V brings to Pts and the healthcare system.
I was REALLY hoping the MITIGATE trial would be presented at ESC but a search of the scheduled presentations did not show anything. I guess we wait till November and AHA.
2 insignificant posters (UK costs and REDUCE-IT Smokers) is all that is scheduled for ESC in August. Very disappointing for a drug being launched in the EU at the same time. Vascepa should have been everywhere and the hot topic but instead almost nothing. WTF!