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Hopefully, will come out earlier, Stock Twits is usually the fastest source. 1-2pm EST.
I suspect we my have a similar trend as Lovaza, it may have to do with how the reps cycle through calls and the tendency for Physcians to start writing more scripts after visit 5. Lovaza's first flatten out at week 8 for 4 weeks, Vascepa slowed after week 13,14,15...we'll see about week 16 today.
Week 17 will include my two off label 3 mo scripts, wonder how many others start to pop up.
25% will die in the next 2 yrs
50% in the next 4 yrs
75% in the next 8 yrs
Using minimal cancer risk (family history), maximal CV risk, Diabetic
http://gosset.wharton.upenn.edu/~foster/mortality/perl/mainform.pl?age=65&sex=male&race=white&height=70&weight=220&education=more+than+11&income=800000&maritalstatus=married&fitness=1st+%28least+fit%29&familyheartdiseases=do&familyprostate=do+not&familybreast=do+not&familycolorectal=do+not&familystomach=do+not&familylung=do+not&familydiabetes=Two+or+more&familystroke=do&geography=Texas&asthma=have+not&diabetes=don%27t+know&bloodpressure=90&smoking=20&spousesmoking=20&alcohol=2+to+3&drivingdistance=12&driversex=male&driverage=70&driverbelt=do&driverspeed=does&driveralcohol=never&stress=3&exercise=sedentary+person&occupation=manufacturing&occupationfather=manual&occupationfirst=non-manual&occupationlast=non-manual&nutrition=3&fatintake=more&depression=am&sexualpartner=0&condomuse=do&sleep=6
Will
Yo...Yoyo88, I occasionally pop over to Adumb Twitter, but have found he will not debate. You make two great points, why the heck would the FDA require an outcomes follow through? Because the FDA recognized the science and want answers to the BIG question, does this save lives and healthcare dollars. Do you think Amarin would spend $50 million dollars a year to do a study they didn't HAVE to do? Hell no! Hence the 40% enrollment and staggered approval Marine-Anchor-REDUCEIT. I agree, "incentive", is the only reason for the requirements and staggered approval here. Ethically not such a great idea, if REDUCEIT results hit it out of the park how many people did we knock off by an inefficient approval. (The FDA allowed 1000's to suffer with Swine flu outbreak, not allowing quicker access to Peramivir and inhalational Zanamivir)
How dare you label Adumb as "irresponsible", are you implying he's OK with people suffering and dying by crushing a small biotech and delaying treatment? If you are, I also agree. DNDN, BCRX, ARNA, AMRN....the list is loooooonnnng. I can spot loser biotech treatments from a mile away, but I'm generally not going to bash them unless provoked. (VVUS).
As far as Herper making a comment, "Nissen's generally opposed to approving new drugs w/o outcome data so I'm not sure his stance predicts FDA", Adumb must be crushed his boyfriend disagrees.
Williams
Biochica, the study results Zip is referring to where laser eye surgery r/t retinal detachments. The results where so good they had to ethically stop it. Today, if you have a detached retina, big problem with DM, they "spot weld" it with a laser. Zip I think was trying to infer that REDUDE-IT could be stopped because of positive results.
I've had this discussion with Akanz and he's convinced the won't end it early like the JUPITER study. I do think they could however modify the study at the time and put everyone on the treatment arm.
Williams
(1) Is there any credence to the proposition that the FDA would not have accepted SNDA for anchor in the first place, if they were unprepared to grant?
Yes, from the last cc
"Let me also note at this point in time, that no other Omega-3 therapy is approved for the ANCHOR indication. The REDUCE-IT trial has an update through our cardiovascular outcome study that is substantially underway. Our enrollment continues to progress well and we have exceeded well over 4,000 patients and we currently have more than 400 sites in 11 countries enrolling patients in the study and continue acceptance to enroll to its full completion of approximately 8,000. As we previously stated, the results of the study will not be available until specified number of cardiovascular event has been observed, the timing of which is not expected in the near term. The current level of enrollment for REDUCE-IT has exceeded the requirement as outlined in our special protocol assessment agreement with the FDA for the ANCHOR indications who have been accepted, which as you know happened last month. This is yet another reason why Amarin is optimistic that the FDA will approve Vascepa from the ANCHOR indications."
(2) How certain is favorable combo result?
Very certain, also from the last cc
"In fact, Vascepa reduced triglyceride levels in the statin-treated group above and beyond statin alone of 65%. While we have not finalized next steps in development of this combination product or series of combination products, we are happy to say that we see progress in confirming the feasibility of special combination products and look forward to providing additional update in this topic by the end of the second quarter."
Note 65% above the statin alone, that's crazy ass good. "Not finalized the next steps", translation 'at this point BP doesn't want us to release any more information'. "Combination product or series of combination", did you catch that series word?
It's truly quite exciting that the only bashing naysayers can come up with is Niacin's outcome study is so bad, Anchor won't be approved. Both Niacin and Vascepa effects some of the same labs, but strong epidemiology related to both Japanese and Western science indicates it's more to do with the EPA levels.
Williams
OB patent 8188146
"Because EPA will compete with AA for incorporation into the Sn2 position of phospholipids, EPA will also reduce the amount of AA incorporated into that position. This is likely to be particularly important in depression, where AA levels are relatively or absolutely abnormally high. EPA itself is a HUFA which can be converted to desirable compounds like prostaglandin I.sub.3 (PGI.sub.3) and prostaglandin E.sub.3 (PGE.sub.3) which have a range of anti-inflammatory and antithrombotic actions which may be particularly useful in neurodegenerative disorders and in depression. The compounds derived from EPA appear to be less potentially harmful than the equivalent compounds derived from AA. Replacement of AA by EPA is therefore likely to be of particular value in all the neurodegenerative disorders described above, where at least part of the damage is attributable to overactive phospholipases which release AA which can then be converted to pro-inflammatory compounds."
EPA:AA ratio can't be denied by the FDA, The USPTO allowed this in the description and the FDA OB'd it.
"fish oil" has nothing to do with Niacin.
Genius, Lets go over Anchor facts first.
SPA study designed by the FDA and Amarin, it met all primary and secondary endpoints. This is success for efficasy. It had no safety issues. Finally none of the data has been subjected to any accuracy issues. All efficasy and safety data for Anchor is included in the Marine review documents, efficasy and safety for Marine has been approved.
So, the what are the possible show stoppers? In my opinion it would be some new found medical issue that raises questions about the safety or benefit of the drug or indication. Like the Niaspan study? In my opinion the Niacin study has ZERO effect on Anchor.
http://www.nih.gov/news/health/may2011/nhlbi-26.htm
Niacin lowered LDL, raised HDL and did jack for CV outcomes.
Does the AIM HIGH NIH study relate to "fish oil"? No Niacin and Vascepa have two separate mechanism of action. The "fish oil" hypothesis is related to EPA:AA ratios. Yes both Niaspan and Vascepa do a lot of similar lab value changes, but Niaspan does nothing to the EPA:AA ratio. The AHA has risks stratification for CV disease and who should maintain trigs less than 500, the Anchor indication. This is the medical need, and one dope cardiologist can't change this, nor can the FDA. Is there a medical need for the treatment of trigs 200-500, yes according to MANY cardiologists.
The failure of niacin does nothing to the medical need, it did raise question to the importance of raising HDL, which has nothing to do with Anchor.
This is the Pre-PDUFA game, that's it. Anchor's chance of approval is very high.
Williams
PS Adam couldn't pass a 10th grade biology final today, don't trust his scientific judgement.
Thanks Kay, quick search showed Marine indication. Hopefully we see a NDA filed soon in Europe.
The Capsule Patent 8445003 is OB'd, this is a new IP wall.
We claim:
1. A method of lowering triglycerides without increasing LDL-C in a subject having fasting baseline triglycerides of 500 mg/dl to about 1500 mg/dl comprising, administering to the subject a pharmaceutical composition comprising at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate in one or more capsules comprising a capsule wall composed of a film-forming material that is free of succinated gelatin, wherein the composition is administered in an amount and for a period effective to reduce triglycerides by at least 25% without increasing LDL-C in the subject compared to a second subject having fasting baseline triglycerides of 500 mg/dl to about 1500 mg/dl who has not received the pharmaceutical composition.
2. The method of claim 1 wherein the film-forming material comprises gelatin, carrageenan, alkylated or hydroxyalkylated cellulose ethers, starch, alpha-starch, hydroxyalkyl starch, sodium alginate, sodium salt of a gelatin copolymer and acrylic acid, hydroxypropyl methyl cellulose, hydroxyethyl cellulose or polyvinyl alcohol.
3. The method of claim 1 wherein the film-forming material comprises at least one plasticizer.
4. The method of claim 1 wherein the at least one plasticizer comprises a hygroscopic plasticizer.
5. The method of claim 4 wherein the hygroscopic plasticizer comprises glycerol.
6. The method of claim 1 wherein the film-foaming material comprises gelatin.
7. The method of claim 1 comprising administering the composition to the subject for a period effective to reduce triglycerides by at least 30% without increasing LDL-C compared to the second subject.
8. The method of claim 7 comprising administering the composition to the subject for a period effective to reduce triglycerides by at least about 35% without increasing LDL-C compared to the second subject.
9. The method of claim 1 wherein said period is at least about 12 weeks.
10. The method of claim 1 comprising administering the composition to the subject to effect a reduction in apolipoprotein B compared to the second subject.
11. The method of claim 1 comprising administering the composition to the subject to effect at least a 5% reduction in apolipoprotein B compared to the second subject.
--------------------------------------------------------------------------------
Description
--------------------------------------------------------------------------------
BACKGROUND
Mixed omega-3 fatty acid esters are typically encapsulated in type 2a gelatin capsules containing gelatin (.about.43.4%), glycerol (.about.20%) and water (.about.36.6%) and do not experience stability problems throughout their shelf life. While chemically modified gelatins such as succinated/succinylated gelatin have been used to encapsulate reactive fill ingredients, such gelatin is not approved for use in the U.S. and other markets.
SUMMARY
We have unexpectedly found that high purity eicosapentaenoic acid (EPA) is more susceptible to oxidative degradation than mixed omega-3-acid ethyl esters. In various embodiments, the invention provides pharmaceutical compositions comprising a fatty acid or a derivative thereof in a capsule shell that resists, hinders, attenuates, or prevents oxidation of the fatty acid or fatty acid derivative, for example to a greater extent than is provided by a standard type IIa capsule shell. In a related embodiment, the fatty acid comprises eicosapentaenoic acid (EPA) or a derivative of EPA, for example ethyl eicosapentaenoate (ethyl-EPA or E-EPA). In another embodiment, the fatty acid comprises ultra-pure EPA.
In one embodiment, the invention provides a pharmaceutical composition comprising ultra-pure EPA encapsulated in a capsule shell, where the ultra-pure EPA has a baseline peroxide value not greater than about 5 meq/mg and upon storage of the composition at 23.degree. C. and 50% RH for a period of time, that ultra-pure EPA has a second peroxide value not greater than about 20 meq/mg.
In other embodiments, the invention provides a pharmaceutical composition comprising EPA (e.g. E-EPA or ultra pure E-EPA) encapsulated in a capsule shell comprising a film forming material and a hygroscopic plasticizer, wherein the weight ratio of film-forming material to hygroscopic plasticizer is not less than about 2.5:1. Further, the capsule shell can optionally comprise a non-hygroscopic plasticizer. In one embodiment, the capsule contains no chemically modified gelatin, for example succinated or succinylated gelatin.
In still other embodiments, the present invention provides methods of treating or preventing a cardiovascular-related disease using compositions as described herein.
These and other embodiments of the present invention will be disclosed in further detail herein below.
Amarin was ask for an expensive outcomes study, It's called REDUCE-IT. It was designed under SPA also. The FDA may get a chance to review the current status of REDUCE-IT and probably the reason they wanted REDUCE-IT 50% enrolled before Anchor sNDA. Early data should point to success when reviewing the JELIS timing.
In fact, the FDA may have reviewed REDUCE-IT data prior to the acceptance of the sNDA for Anchor.
If the FDA intends to not follow the binding SPA agreements: 1) The director must document it in writing and provide it to the sponser 2)The sponser is given a chance for a meeting with the director to discuss the scientific issue.
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080571.pdf
Page 10, but read the entire document. All Anchor data has already been review and can be found under the Marine review documents.
Anchor will be approved on or before December 20th PDUFA.
Great, thanks for sharing!
Last I looked we had 14 OB patents, we now have 16...when did this happen?
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=202057&Product_No=001&table1=OB_Rx
At this point it really has turned into a nonissue. Yes it was a big deal 9-2012 through 4-2013, but Amarin has now changed gears into the Anchor launch. BO won't happen this close to Anchor, Co-launch partner is the more likely senerio.
I do believe the lack of NCE/NME hindered a BO in the fall of 2012.
Understand the science:
The arachidonic acid (AA) to EPA ratio is another important measurement of risk for atherosclerosis and its consequences.38 AA is an omega-6 fatty acid that is metabolized into dangerous mediators of inflammation, including leukotrienes and prostaglandins, while EPA tips the scale in the direction of anti-inflammatory activity, so EPA helps downregulate these pro-inflammatory agents. A lower AA:EPA ratio is correlated with reduced risk for cardiovascular diseases.39
http://www.lef.org/magazine/mag2010/may2010_Optimize-Your-Omega-3-Status_02.htm
http://www.drsears.com/DesktopModules/EngagePublish/printerfriendly.aspx?itemId=68&PortalId=6
In conclusion, this study confirms the positive effects of n-3 PUFA supplementation in the treatment of elderly depression. It also demonstrates that n-3 PUFA status may be monitored by means of the determination of whole blood AA/EPA ratio.
http://www.nutritionj.com/content/pdf/1475-2891-11-82.pdf
JL, is this an over reaction? In searching for an EPA:AA blood test, to track my ratio, I came across numerous Endocrine, CV, and diet related research. The evidence points to less chronic disease conditions with ratios of 1:1.7 to 1:3. While most on a Western diet are 1:25, the Japanese population has a considerably lower ratio closer to 1:3 and less chronic inflammation diseases, including CV disease.
I believe high EPA:AA ratio's is the "American Scurvy" of the 21st century. http://en.wikipedia.org/wiki/Scurvy
Amarin should consider filing an sNDA for Vascepa to treat high EPA:AA ratios based on the massive scientific data and epidemiology comparisons with inflammatory diseases. The filing would not be based on one specific disease, but on a dietary deficency causing diseases just as bad as scurvy. I think we have all been lost in the forest, only seeing the trees of cardiovascular disease.
Thoughts
Williams
EPA:AA ratio blood test....great article
http://www.endocrine-abstracts.org/ea/0029/ea0029oc19.1.htm
NCE is now irrelevant with short term valuation. End of story. Stock closed flat on low volume after FDA failed to show up for work, again. They where too busy writing BS MAPP policy to make a real decision.
At this point it's irrelevant. The FDA has proven incompetence, and NCE has no value over NME for Anchor.
Patent's have NEVER expired with NCE/NME, Amarin dominates until 2030. 17 years of Billions + revenue...
Williams
Here's one of many studies related to EPA, EPA:AA ratio's and ADHD
http://openi.nlm.nih.gov/detailedresult.php?img=1971271_1475-2891-6-16-1&req=4
Is It Asperger's Syndrome or ADHD? The two are closely related and some experts believe they are one in the same. The Asperger's diagnosis just recently got rolled into the Autism spectrum. About 1:150 children born today are on the spectrum.
http://www.additudemag.com/adhd/article/7952.html
My 10 yr "Asperger's" (now considered high functioning Autism) son is starting Vascepa off label for control of ADHD symptoms. EPA blood levels and EPA:AA levels is the target and nothing overthecounter or prescription wise gets EPA blood levels "therapeutic" as safely as Vascepa.
FACT:
8 gms Lovaza (in adult) = 80 mcg/ml EPA blood plasma levels
4 gms Vascepa (in adults) = 347 mcg/ml EPA blood plasma levels, with fewer side effects and no Afib warning.
DHA plays a role in brain development but functional everyday physiology EPA is the key player.
Williams
Finance
Chab hit the nail on the head. Claims cleaned, the Statin combo is Crestor, 200-500 trigs, up to 5 grams of "Fatty Acids" composed of 90% EPA, and 4 capsule dose.
Not likely to be issued until later this year, fall maybe IMO.
Can't get OB'd until we are approved for Anchor.
For Amarin to seek approval they would need a small dosing "phase 1 study", file sNDA for combo using 505 (b) (2) and run the 10 mo PDUFA cycle. Efficacy and safety data pulled from Marine and Anchor phase 3 studies.
This Combo drug will be sought after and approved late 2014 early 2015. Unless Amarin's waiting for hydroxy-lipitor NCE possibility. IMO, why wait...flood the market with Lipitor/Vascepa and Crestor/Vascepa and let physicians choose the statin.
Yes, combo/Anchor 200-500 has more value to BP, especially if Hydroxy-Lipitor combo can garner NCE status. If Pfizer M&A, they could have this combo on the market late 2014.
Williams
Thanks for posting your Level 2 for those to note the robot sell orders at 6.98 for 400 shares. All part of rapid computer HF trading stealing weak shares and manipulation of options. All OK by the SEC. The other side of the game is to find the heavily shorted stock no one thought could make it, buy a lot, wait, entertain yourself with loser HF minimum wage employees on the web, wait some more, and take your money to the bank. Repeat...retire.
Williams
You could actually see it if you searched SEC filings, no insider sales. Only HF manipulation, I've seen it thousands of times and have profited on HF being ignorant on scientific matters. Stock manipulation on good news is HF favorite weapon, it's proving worthless with Amarin longs that just have to wait. Time is on our side.
Many links to EPA effects on Psychiatric conditions:
Sear's:Dr. Sears hypothesized, “It is this anti-inflammatory action that is responsible for the neurological benefits. This is confirmed by numerous studies in which DHA has little, if any benefits, in treating depression or attention deficit hyperactivity disorder, whereas fish oils rich in EPA do have remarkable benefits."
http://www.prweb.com/releases/fish_oil/omega_3/prweb4725774.htm
Autism
http://www.dailymail.co.uk/health/article-373833/How-fish-oil-unlocked-autistic-son.html
The fact is this is what I'm using it for, off label with a prescription written by a Pediatric Pschiatrist with a very busy autistic population. From memory, he could pull out more "fish oil" studies than me. If need be ZBD can verify this, as I have offered to share the effects with him.
Guarantees us two new scripts;) LOL. (Out of pocket too, most parents of autistic children spend thousands out of pocket for treatment by the way)
Thanks for your Amarin information, it seems you have made a mistake, would you like to correct yourself?
JL & ZBD
Just got two scripts off label. One for me. One for my son, 10 yo Asperger's . Armed with Dr. Sear's it was easy.
Williams
Possible, they also have a ton of cash. Yesterday they met with Leerink.
Amarin shareholders really appreciate Adumbs thoughts. He's as bright as they come, and extremely honest.
Thanks for sharing I will sell all my shares....above $50;)
Yes, I agree with your assessment. Amarin has consistently started with broad patents, then narrowed them down with follow up patents. It was unexpected that this got OB'd.
Williams
BIDing War, yes that sounds about right. Although I see more than one company joining together for a BO senerio. Merck & Pfizer.
How big is this '899 patent news,?
Big enough that the Public PAIR's USPTO site has crashed.
Williams
Two very important points:
1)"fixed or non-fixed dose"
2)"Amarin plans to list this patent in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book, after issuance of the patent."
The patent wasn't watered down, it was modified to pass quickly, and ambiguous fixed or non-fixed dose to get OB'd. Very smart. Stronger wording will likely get approved later this year, but may not be able to get OB'd because currently Amarin doesn't have an approved combo.
Williams
"Through our findings from conversations with thought leaders and other clinicians during the launch of Vascepa, we've confirmed that many patients on therapies intended for lowering triglycerides are also on statins. The claims in this allowed application cover the administration of a pharmaceutical composition comprised of EPA in conjunction with a stain, using either a fixed or non-fixed dose, to lower triglycerides without increasing LDL-C, otherwise known as bad-cholesterol," stated Joseph Zakrzewski, Chairman and Chief Executive Officer of Amarin.
A Notice of Allowance is issued after the USPTO makes a determination that a patent can be granted from an application. The issued patent would have a term that expires no earlier than in 2030. Amarin plans to list this patent in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book, after issuance of the patent.
Zum- "No parking, tow away zone". That's what '899 is, many others will follow. It's clear by the title the intension of the patent, no one will beat Amarin to a hard core EPA combo patent with Amarin having '899 being the first.
https://www.google.com/search?q=no+parking+tow+away+zone+sign&ie=UTF-8&oe=UTF-8&hl=en&client=safari#biv=i%7C1%3Bd%7COZ5X66E4XnOQPM%3A
Congrats Amarin,
Williams
NOA for '899 should come this week, might be an interesting options Thursday.
Between Notice of Allowance Data Verification Completed and NOA for '145, '885, '153, '889 all under 6 days.
Zumantu
"13/417,899 Pharmaceutical compositions comprising EPA and a cardiovascular agent and methods of using the same"
The claims support the title, "compositions (plural;) comprising of EPA and a cardiovascular agent" As you state the claims where revised 11-05-2012, they all refer to the "obvious" combo drug.
15. (probably renamed #5 after the other 10 where canceled) "The method of claim 11, wherein the statin is selected from lovastatin, mevastatin, pitvastatin, pravastatin,rosuvastatin, fluvastatin, atorvastatin and simvastatin." This is the combo list that apply's to the combination product.
The claims where cleaned up on 11-05-2012, nothing chaged making this anything but a combo patent "comprising EPA and a cardiovascular agent". Does this help?
Williams
Notice of Allowance data verification directly proceeds, the "Mail Notice of Allowance"...Amarin has made PR's after this. Since data varification was done 5-15, Mail NOA should happen any second....
PR should follow.
Williams
Leerink is arguably the best when it comes to valuing assets of a pharmaceutical nature. The reason is MEDACorp, a network of 30,000 healthcare professionals that share their knowledge with Leerink.
I find it quite a telling Pfizer's management is meeting with Leerink on the day Amarin gets NOA for combo. Then we open with 2 million shares traded...
Williams
Congrats Amarin on the first NOA for combo product.
'899 NOA data verification complete dated 5-15, but showed up today.
Williams
Zumantu, thanks for your insight, "primary care" positions:)
It may have to do with how the reps rotate through their list of calls. The flat/drop weeks may be the start of the 5 visits JZ mentioned in the cc. We look to be on week 4 and should expect it with Sunday's numbers.
"For a new drug launch particularly for drugs which have prevented a fair piece for chronic ailment, day sales suggest that approximately 5 to 10 businesses are needed to change practice patterns. We are witnessing that for those clinicians who have been visited more than five times with the levels of script writing is the highest." page 2
http://seekingalpha.com/article/1421861-amarin-corporation-ceo-discusses-q1-2013-results-earnings-call-transcript?page=2