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Is late breaking the only way to address long standing contraversy? Why not publish the results when they were available ? Why wait for the late breaker.
If th strength team knew the answer, by withholding it were they not doing disservice to.patients?
They could not publish it because they did not have the full data or finalized results before the due date.
Timing was the only reason.
Again, why important question needs a late breaking answer? If it important and if the results are known, should they not be published immediately?
Amarin filed the paper with Judge Du stating indirectly stating that they are not party to the 24/60 appeal. Judge Du used it against @marjac to say the party that owns the patent is not part of the case. You as shareholders are not an interested party.
I completely agree. SC said the matter on the case is not something we are going to entertain.
@marjac has the best shot with the 24/60 appeal on the Marine patent. This is a completely different appeal than the one SC was asked to intervene.
Epidemiology, Big Data and Precision Medicine
Fish Oil, Fancy Drugs, and Frustrations in Lipid Management
18611
STRENGTH Trial: Cardiovascular Outcomes With Omega-3 Carboxylic Acids (Epanova) in Patients With High Vascular Risk and Atherogenic Dyslipidemia
A Lincoff1, Stephen J Nicholls2, Michelle Garcia3, Dianna Bash4, Christie M Ballantyne5, Philip Barter6, Michael H DAVIDSON7, John J Kastelein, Jr8, Wolfgang Koenig9, Darren K McGuire10, Dariush Mozaffarian11, Terje R Pedersen12, Paul M Ridker13, Kausik Ray14, Brian Katona15, Anders Himmelmann16, Larrye E Loss17, Martin Rensfeldt18, Torbjorn Lundstrom19, Rahul Agrawal20, Kathy E Wolski21, Steven E Nissen22, for the STRENGTH Trial Investigators; 1CARDIOVASCULAR MEDICINE, Cleveland Clinic, Cleveland, OH, 2Monash Cardiovascular Rsch Cntr, Victorian Heart Institute, Clayton, Australia, 3Cleveland Clinic, Cleveland, OH, 4HVTI -C5Rsch, Cleveland Clinic, Shaker Hts, OH, 5-, Baylor College of Medicine, Houston, TX, 6Univ of New South Wales, Sydney, Australia, 7-, Univ of Chicago, Highland Park, IL, 8-, Academic Med Cntr, Amsterdam, Netherlands, 9Dept of Cardiology, Deutsches Herzzentrum Muenchen, Munich, Germany, 10-, Univ Texas Southwestern Med Cntr, Dallas, TX, 11Friedman Sch of Nutrition Science & Policy, Tufts Univ, Boston, MA, 12Oslo Univ Hosp, Oslo, Norway, 13-, Brigham and Women's Hosp, Boston, MA, 14Dept of Primary Care and Public Health, Imperial College London, London W6 8RP, United Kingdom, 15Astra Zeneca LP, Gaithersburg, MD, 16Global Clinical Lead, R & D, AstraZeneca, Molndal, Sweden, 17-, Astra Zeneca LP, Gaithersburg, MD, 18R & D Molndal, AstraZeneca, Molndal, Sweden, 19Astrazeneca R&d, Molndal, Sweden, 20-, Astra Zeneca LP, Mölndal, Sweden, 21HVTI -C5Rsch, Cleveland, Cleveland, OH, 22-, Cleveland Clinic, Cleveland, OH
Background: Considerable interest has focused on the potential for omega-3 fatty acids to lower cardiovascular risk. Observational studies have demonstrated an inverse association between dietary consumption of either fatty fish or omega-3 fatty acids and prospective risk of cardiovascular events. Additional studies have suggested that red blood cell concentrations of either eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) are inversely correlated with cardiovascular risk. Biomarker studies have demonstrated that omega-3 fatty acids exert favorable effects on lipoprotein metabolism and inflammatory, oxidative, thrombotic and arrhythmogenic factors implicated in cardiovascular disease. It remains uncertain whether omega-3 fatty acids reduce cardiovascular risk. Objective: A carboxylic acid formulation of EPA and DHA (omega-3 CA, Epanova™) is administered as a free fatty acid not requiring hydrolysis by pancreatic lipase during intestinal absorption, eliminating the need for co-administration with a high fat diet and resulting in greater bioavailability compared with standard omega-3 ethyl ester formulations. This omega-3 CA has been previously documented to have favorable effects on lipid and inflammatory markers. The STRENGTH Trial (NCT #02104817) assessed the effects of omega-3 CA on cardiovascular outcomes. Design: A double-blind, randomized, multicenter trial (enrollment October 2014 to April 2017; study termination 8 January, 2020) comparing omega-3 CA 4 gm daily (n=6539) with matching corn oil placebo (n=6539) in statin-treated participants with high cardiovascular risk, hypertriglyceridemia (triglyceride levels ≥180 mg/dL and <500 mg/dL) and low levels of HDL-C (HDL cholesterol <42 mg/dL for men or <47 mg/dL for women). Settings and Participants: 13,078 patients were randomized at 675 academic and community hospitals in North America, Europe, South America, Asia, Australia, New Zealand and South Africa. Main Outcome Measures: The primary efficacy measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and hospitalization for unstable angina. Changes in lipid and inflammatory biomarkers, as well as safety and tolerability were evaluated. Results: At a time when 1,384 patients had experienced a primary endpoint event, the independent Data and Safety Monitoring Board recommended termination of the trial for futility. The median patient follow-up was 38.8 (interquartile range 32.8, 45.4) months. Vital status was recorded in 99.8% of patients, and 96.6% of patients had complete follow up of for assessment of the primary endpoint. The final primary results of the trial will be presented.
Author Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2020 Online Program Planner and search for the abstract title.
Key Words: Fish oils; Triglycerides; Hyperlipidemia; Arteriosclerosis; Prevention
Rafun- May I present to you the STRENGTH TRIAL
https://www.ahajournals.org/doi/10.1161/CIR.0000000000000940
What's the long short logic here? Take a step back and ask a simple question-
A abstract should be late- breaking and not a conventional submission because?
You will be hard pressed to come up with a answer that has a basis in science.
The only rationale for late breaking is that data needs to be presented at big conferences to a wider audience. This is the need of the company wanting to present.
Unfortunately , the study will end and can be analyzed only at the last minute ( and way past conventional deadlines). This is the reason why we request the organizers to let us present the data at the last minute
My ears are open to any other reason you may have to offer.
I do not and I do not think it is the placebo.
Just the way FDA said aducanumab works because we say so DESPITE zero evidence, in today's age scientific evidence is not a requirement to demonstrate efficacy and effectiveness.
Nope responded to it.
I do not ignore anything on purpose.
Exactly.
1. We do not have the data by the conventional deadline for asbtracts and posters
2. We would still like to present it. We believe it is important (isn't every trial important ? Otherwise what is the value of doing it ? )
3. Our data release will also have market implications. We need to ensure the data is presented at a non- market time.
4. We also need the data to be embargoed for reason #3. Nothing should be revealed before the said time .
The question- in absence of the above requirements from the presenter, what is the scientific value of late breaking ? To best of my knowledge - NONE
All to ourselves.
Late breaking- what's the function of that in a scientific conference ? What exactly does it achieve beyond media attention? The biggest trial that will reveal whethere humans will live for 100 years on "nuts" will be presented in 6 days 39 minutes and 24 seconds. The count down has begun . Now it is a wait . Will the reveal provide the answer?
Steve jobs marketing gimmick - AND ONE MORE THING. Let me open the yellow paper envelope!
Are we all to assume that the very busy cardiologist (outside of networking benefits) are going to the conference in anticipation of a the next break through , reveal that will be unleashed at 5:39 pm on a website and door open at 8:45 am in the morning for the reveal?
Late breaking have a pure market function - anticipation , 'media buzz and finally commerical implications for a company. Unlike iphone 20 /21 sneak peak , none of the participants have any value in knowing about something that may have value years down the line.
I do not think late breaking is a function of importance but more likely a function of how and when data is released. The need to get eyeballs and the buzz . It is more of a marketing function than scientific importance.
I hope I am wrong , but covid-19 trials are all based on one principle
Let's throw something at virus . Something may stick.
Yes. But they will play the same games.
They will look at all combos and present 0 vs 6 wk but not 6 wk Vascepa vs 6 wk placebo, etc.
All I am saying is CVD is the forte to fight for.
Other areas are just exploratory. Noting wrong in testing the covid hypotesis. But given the very broad importance of EPA in human body over long periods, trying to establish 2-3 week cause effect in a infectious disease is that valuable
We should not make an assumption that FDA approved drugs based on science and evidence ( They do believe in quackery - see Biogen Alz drug)
But until recently the approval of Remdesivir was based on clincial data where it was shown to be marginally "useful" in early covid.
EPA may have a long shot at that outcome.
Designing Good clinical trials is hard. Successful clinical trails are a miracle.
Sleven,
These are acecdotal evidence. Hence we have double blinded clincial trials.
However, after aducanumab , as long as we show FDA that smoking is indicative of cancer free life using my grand pa as an example , they will see the correlation is causation and approve the drug.
(sarcasm)
We can have a scientific debate.
#Aducanumbab
They looked hard enough and found that only one truly with a high dose group "retrospectively" found statistical significance which clinicians acknowledge is not clinically meaningful.
Logically, when you look hard enough and you see statistical evidence , it is reasonable to acknowledge that everything worked and FDA nods in tandem !
No I am not. It "may" show promise just like Remdesivir but nothing that will be ground breaking.
Long-term EPA effects is a different story vs 1-2 wk treatment.
Everything is statistically significant if you look hard enough. Higher sample size will gurantee p<0.05.
The question is effect size, clinical significance, etc.
We will see ?????
If Fda is on our side, they may insist that we the clinical trial be negative to secure approval for the new indication.
Any indication, the drug truly works, they may want more studies to show that it was not because of MO.
You realize that this is going to look for all parties involved. FDA told that they can not enforce the Congress mandate to ensure safe and effective drugs reach patients.
Companies like these have massive data bases to the individual doctor level . All big pharma use it
https://www.iqvia.com/locations/united-states/solutions/life-sciences/information-solutions/essential-information/prescription-information
Sony Vs Universal can grant the victory
In 1984, the Supreme Court held that “the sale of copying equipment, like the sale of other articles of commerce, does not constitute contributory infringement if the product is widely used for legitimate, unobjectionable purposes. Indeed, it need merely be capable of substantial noninfringing uses.” Sony v. Universal City Studios, 464 U.S. 417, 442 (1984). Under this standard, a copy control circumvention tool would not violate copyright law if it were “widely used for legitimate ... purposes” or were merely “capable of substantial noninfringing uses.” Id.
WIDELY USED FOR LEGITIMATE PURPOSES
If Amarin shows evidence that generic Vascepa is PRIMARILY used for off label use, the sale of equipment (AKA Genric Vascepa ) for off label use, the equipment aka DRUG will violate patent law.
Inducement to prescribe brand is kickback. !
Doc- What is the basis?
Amarin-Generic is inferior
Doc- how do you know?
Amarin- internal tests
Doc- FDA disagrees
Amarin- FDA is not doing its job
Doc- Neither are you. Out of my office .
Policing other generics by brand is a dangerous precedent. No major pharma will do that . It is the job of FDA.
Just imagine pharma going after generics and the headline
Amarin asks FDA to shut down competitor that sells drug at lower price, etc
CVD is huge.
Either @marjac delivers a win or the lawyers are Amarin are creative with and convince the judge that the only reason generics are on market is for CVD indication.
The best argument for induction is to get access to the prescription data for generics and the indications they were used for off label. Convince the judge that if it primarily for CVD then :
1. Generics depended on FDA label ( AB rating) to be aware that infringement will happen
2. Generics were expecting doctors to infringe. By supplying in excess, generics. "FACILITATED" infringement
3. Insurers knew off label use will infringe patent but FACILITATED AND approved off label use, thus "encouraging" doctors go prescribe generic for off label use.
I am not aware of the word facilitate being used bin patent cases in US. It is time to bring it in focus. This is different from inducement but targets the same end point of infringement
In EU , it is settled as suggested by Mylan Novartis case
On 29 September 2020, the Provisions Judge in The Hague granted Novartis a cross-border injunction against certain companies of the Mylan group. French company Mylan SAS is the holder of the marketing authorisation of a generic version of Novartis’ Exjade® product. Dutch company Mylan NV is the mother company of the Mylan group and controls Mylan SAS. Mylan SAS was co-ordinating plans to bring its generic product on the market in various European countries during the lifetime of Novartis’ supplementary protection certificate (SPC) to Exjade®. The judge held that this behaviour qualifies as the facilitation of patent (SPC) infringement in the relevant European countries and that such behaviour is unlawful. Mylan SAS and Mylan NV were injuncted from facilitating any infringement in the relevant European countries.
The production protocols are "validated" to produce the same product that was approved.
Can a company fudge records and have inconsistent quality control check? YES. This will be considered out of compliance and violation of GLP validated processes.
FDA can shut down the WHOLE plant for failing on one drug. Can a generic company making 10-50 drugs at the plant afford this?
Once it is invested, the process is hepatic, renal, extra hepatic clearance, metabolism and elimination !
When you do bioavailability studies you compare AUC , Cmax, AUC -0 min to infinity.
All the post ingestion process are captured by we measuring this.
bioavailability is the amount of the drug that teaches systemic circulation . This is captured by AUC. When you compare AUC of different brands, you establish bioequvalence.
S
Prepare-It will not add any value. At best, indicative , suggestive, likely , priomising, etc will be the buzz words around it. Nothing more.
CVS fills 36.5% of US prescriptions
You are mixing products. Concerts was what we call as modified release product. The drug deliver system was the key to the product characteristic, including amount is blood. Also the conc profile is very critical for the pharmacological response of this drug in ADHD and other neuro.indicztions
Vascepa is a liquid gel gelatin product . All the drug dumps in the GI tract once the gelatin disintegrate in stomach acid.
EPA purity is the it attribute. If HIKMA is delivering bioequivalent product, which they should, it no different from Vascepa
There is no product differentiation for Vascepa and the only question to ask is
What makes anyone believe that Hikma EPA ipresent in the caplet is less than what the label claims.
If the do have a lower quantity than the label, this is misbranding and they have to pull out the product. There is no reason to believe that they will do that. Also, FDA is regularly required to test batches. Mfg, have to send samples of new batches to FDA. Most the them sit trying shelf but o FDA will randomly analyze them to see they are are compliance. The companies are also required by regulation to maintain a testing long on new batches. Can they fudge data? Absolutely !!! Will they do it ? Not likely. As I had noted , the risk of being shut down is far higher and not worth it .
The most common generic issues are not with active drug but poor compliance , record keeping and some impurities in the main drug for which they get cited. it will be very rare that thw drug fails the content test
The pill burden has a direct impact on compliance. That's the issue and it adds up with passing age.
I am not a legal expert. But some independent FDA approved lab will have to do the content uniformity and dissolution studiesto show that the drug batch fails to meet the label requirement , provide the info to all agencies and request withdrawal of the drug.
Amarin can initiate the studies and get the data in a matter of days. Will they do that ?
I don't know. I am open to science. If a person has rationale arguments supported by facts, I respect it.
I thought this person was right with his argument before Reduce -It .
What I liked more was his acceptance that when new data emerges, you acknowledge it and don't go about conspiracy like Nissen. They even explained why MO is a no issue.
Further more, with the Apo-B logic and making fun of Amarin and it's lawyers, the person also laid out an argument in support of the patent.
Always respect the science. And if the messenger ia convening the right message, they deserve my respect.
This person Swan was short Amarin before Reduce It data. The reasoning was spectacular based around mineral oil. I have not seen anyone make such a solid argument.
They also openly claimed after reading the FDA briefing document that he is certain that MO is NOT an issue.
The basis was science as to why MO is not an issue and the trail should be treated as a well executed study.
The dope Nissen should read it before spreading all the nonsense on why Strenghth failed but reduce it succeeded.
Here is the persons post in SUPPORT of Reduce it
https://twitter.com/InvestorSwan/status/1194322069430734848?s=20
Seems to me as one of the best scientific minds wasting his time on twitter. People should just hire this person and get some due DD from them.
This will have to go to FDA first. It will be a crime per FDC 1952. All generics when approved need to meet the defined standards.
Either FDA is incompetent or willfully ignorant . As agents of law enforcement with the authority to act, they deserve the blame and not HIKMA for doing the wrong thing.
My personal belief is FDA is incompetent and when the cat is away, mice know how to play.
https://www.law.cornell.edu/uscode/text/21/352
Absolutely! I liked the this person presented that the emperor has no clothes making a mockery of the ruling but also giving Amarin the treatment they deserve.
GVs by design are NOT inferior to branded. If they are , FDA needs to step in. It is the FDA sleeping at the wheels.
I follow this person on Twitter. Seems mostly factual and knows stuff. Makes a lot of fun of Amarin and it's lawyers.
You may want to run this by your statistician who was the expert in the filing. I had shared this with Hindkush.
This could be truly new evidence that can be argued the judge should have known. This is for the APO-B patent 715 and 717 not Mori and Hyashi
Saluti, here is your unroll: @InvestorSwan: 1. Taking a dig at for fun. This has nothing to do with the drug or the clinical outcomes or the role of… https://t.co/hCRt7kIDcJ Talk to you soon. 🤖
— Thread Reader App (@threadreaderapp) September 24, 2020
@marjac Another argumentfrom Judge Du that was definitely full of arrogance was I took years to rule on the patent case displaying my ignorance in all its Glory. How come you did not anticipate my stupidity and file Rule 36. Waiting after my ruling is untimely and simply not acceptable in Du's court.
I am guessing the appeals panel will truly recognize this as an abuse of power by the judge.
Is Bhatts clarifying of existing data be considered new? Amarin simply refused to acknowledge it's existenc.
@marjac
c) Timing and Effect of the Motion.
Tming. A motion under Rule 60(b) must be made within a reasonable time—and for reasons (1), (2), and (3) no more than a year after the entry of the judgment or order or the date of the proceeding.
(1) mistake, inadvertence, surprise, or excusable neglect;
(2) newly discovered evidence that, with reasonable diligence, could not have been discovered in time to move for a new trial under Rule 59(b);
(3) fraud (whether previously called intrinsic or extrinsic), misrepresentation, or misconduct by an opposing party;
Judge Du threw a ruckus over timing of the motion calling it untimely.
1, 3 is something that can be easily explained .
Regarding 2, how can Mori and Hayashi be considered newly discovered evidence? Can it be argued that the Judge failed to recognize this basic statistical fact due to defendents deceipr. The evidence which was obvious needed more clarification based on original data and when presented with more factual context becomes new evidence ?
What line of thought will adequately hit 1, 2 and 3 such that timing is a moot point?
There you go Sleven. I was quite positive that someone had the 500 mg approved.