Here is the response I wrote in another debate. Please do not call me a basher as I'm using this forum for a positive debate and discussion. This is my personal opinion and I respect everyone elses opinion here and would appreciate constructive/intelligent responses.
"The EPA in Lovaza and Vascepa is the same chemical, an ethyl eicosapentaenoic acid. Please see the package insert for the chemical structure, formula and weight under the description heading. How can you say it's different? All bond structures are the same cis-trans position even though its drawn with a slightly different spatial orientation in the Vascepa label, it's the same structure chemically and pharmalogically. The chemical IUPAC names (EPA ethyl ester vs. icosapent ethyl) have the same meaning, and are technically acceptable. You can think of the names as synonyms for each other when you name them chemically. Please see here on the right side of the page for acceptable names . Please see the clinical pharmacology section of both Lovaza and Vascepa and you'll see both have a very similar mechanism of action listed in the insert with the differences in language likely being based on the companies' own studies and the point in time in which each respective product was approved and how many studies were available to supplement the mechanism of action since their respective approval.
I agree Vascepa and Lovaza are different formulations and contains differing amounts of EPA in each product with Vascepa containing more. I agree AMRN found a manufacturing niche in which it was able to extract pure EPA > 96% with NO DHA. I agree the FDA seems to list Lovaza as omega-3-acid ethyl esters versus Vascepa as icospent ethyl thereby inadvertently possibly classifying each drug as different which is a pro-side argument. I believe the FDA makes clear that EPA and DHA are the active moieties in the package insert of Lovaza when it gives specific descriptions of EPA and DHA and characterizes both chemical structures. I believe they reiterate EPA and DHA are the active moieties when they discuss pharmacokinetics. That brings me to the next point....
Again, if we go back to the basic definition of NCE defined by the FDA, "A 5-year period of exclusivity is granted to new drug applications for products containing chemical entities never previously approved by FDA either alone or in COMBINATION." COMBINATION is the key here to the argument in which AMRN should NOT get NCE, but be covered by the Hatch-Waxman Act.
*** continued next post
The 1984 Hatch-Waxman Act (Drug Price Competition
and Patent Term Restoration Act)
• For new molecular entities, Hatch-Waxman allows
patent term to be extended for up to 5 years
– including FDA review time and up to one-half the time
from when clinical trials start to when an NDA is filed
• Hatch-Waxman also provides additional periods
during which the FDA may not approve a generic
• New combinations, new dosage forms, and new
uses receive three years of exclusivity
New chemical entities are approved under the New
Drug Application (NDA) process
“Extending patent life through minor changes”
• Pharmaceutical manufacturers may apply for patent
extensions for minor changes in method of delivery
or type of capsule
• Generic drug manufacturers are blocked from
marketing a drug until a patent dispute is settled
Patent life may be extended through reformulations
New formulations (many drugs)
• Controlled-release (CR)
• Sustained-release (SR)
• Extended-release (XL)
• Long-acting (LA)
New patents are granted for
• Combination drugs
– Advair (fluticasone / salmeterol)
– Combivent (albuterol / ipratropium)
– Bidil (hydralazine / isosorbide)
– Fosamax Plus D (alendronate / vitamin D)
New uses can extend patent life
(Names may change)
I don't think ARNA is a good example . They had a lot of drop outs in their trails.....I think JL addressed that some time ago. There's a real question on compliance .....big issue with all drugs .....likely to be less so with Vascepa.
Regarding valuation .... Markets can be irrational for long periods. Early 2011 AMRN was around $20 ......no patents , no FDA approval , certainly no NCE or NME..... just some speculation on a buyout.
Here we are about 18 mths later with an FDA approved drug , some patents a good chance of an NCE .....some speculation on a buyout ......and where do we trade .....at about half the price in early 2011 !!!!
I've been buying practically all week .....ever since your " blood on the streets " comment .......followed by your " I took a blood bath " comment which encouraged me to buy even more today .
So now I'm a little worried .....no comments about blood tonight.
I'm gently ribbing you ( is that the correct phrase ) don't mean to be sarcastic .....but I've always found it best to trade opposite my emotions.
So if you decide to do a Buzz Lightyear " we are going to infinitely and beyond " ....you'll let me know first right ....cos you know what I'll be doing .
All the above expressed in jest ...may not come across that way in print ...but that's my intention.
On a serious note ......There is always risk in the market ...even more with Biotech . For myself tho , the fundamental story for AMRN is sound. The drug works and will be used by millions as fast as they can produce it. ....what's that worth a year from now ?
I''m willing to bet more then 11.50 a share .....It may go lower first but if some one starts screaming " blood in the streets " quote Baron Rothschild to them " time to think about buying "
Your comment is cogent
but your arguement is akin to "How many Abgels dance on the head of a pin" The crux of the matter is that AMRN's lack of EPA, changes the LDL,and is considered a new moiety. The lack of elevation of LDL is key. Looked at
under favorability egis FDA will in all
likelyhood allow for
The crux of the matter -- indeed, the only relevant issue for NCE status under the law, is what the FDA determines is the active moiety in Lovaza, and whether the description of the active moiety as "ethyl esters" means an inseparable combination of DHA and EPA, or both DHA and EPA (which are both ethyl esters) individually.
I am a lawyer also and I disagree with Circle. I think the fact that Amarin had a high profile meeting with FDA to which it took the biggest name lawyers it could find to try to persuade the FDA of its position is not at all a good sign as to the NCE issue. Nor was Joe's demeanor on the CC indicative of an expectation of NCE status. As I have said before, I think the matter is a coin toss at best. If I had to bet - I would say "no" on NCE status. Just my opinion, but I have read a lot of FDA decisions on NCE status, all of the approval documentation in connection with Lovaza, as well as the relevant statutes. I wanted to be persuaded that NCE status will granted but after chewing everything over, I just can't get there. I think the arguments pro and con have been set forth well and we will see soon.
The drawings of the Lovaza EPA ethyl ester vs. the Amarin icosapent ethyl are different. I am not a chemist, nor did I play one on TV, but they are drawn differently. Not sure what the various bars, circles and lines are called, but the Lovaza drawing has one peak to the left of the circle over the double bars, and then a trough. The Vascepa drawing has two peaks to the left of the circle and double line. As I said, I am not a chemist, but these drawings do not appear to be the same to me.
Show me one study and regulatory approval that shows DHA is active in terms of reducing triglyceride. In fact Amarin confirmed that DHA may be harmful, as when DHA is removed, LDL is no longer elevated.
The fact is GSK has never conducted any trials to show TG effect of DHA when added to EPA, or vice versa, therefore, they can not claim either EPA or DHA as stand alone active moiety, the two had to be lumped together to qualify as active moiety and a NCE. No one can claim EPA as an active moiety until Amarin showed EPA stand-alone is effective.
Thank you for this analysis and for listing your credentials. With all due respect this is a legal issue, not a scientific one. While your characterization of EPA was fine your legal analysis of active moieties and NCE was way off. Your plain reading of the statute left much to be desired especially when there is precedent for the FDA granting NCE status to previously approved ester active moieties to NDAs that achieved more pure forms of the drug in question. See heparin and Lovenox. A plain reading of the statute in such a case is sophomoric. I am a practicing attorney. Id say it is very certain NCE is granted.
Completely agree this is a legal issue, one that is open to much interpretation. The lovenox to heparin analogy is not quite the same situation here, as heparin has a different chemical formula, chemical weight and different physiochemical/biologic properties from LMWH. The science is complex in this scenario and I won't go into the details.
Switching to the Lovaza=Heparin to Vascepa=LMWH is not correct. The chemical structure and weight of EPA is the same in Lovaza and Vascepa and not in Heparin/LMWH. Mechanism of action is the same (same ingredient) in the Lovaza/Vascepa and slightly different (effects on factor Xa) in the Heparin/LMWH scenario. Pharmacokinetics also also different in the Lovenox/LMWH scenario. Kinetics would be the same in the EPA.
I agree, its a legal matter , not scientific
The fire power they brought to bear for the June Orange Book / FDA meeting was substantial
How would you expect Amarin's counsel to have represented their case for NCE?
i'm >75% in favor of NCE and here is why
First, what is obvious is that no clear cut argument can be made either way, for or against. That would make odds of NCE approval appear to be roughly a coin toss.
But all this technical analysis to arrive at a rational conclusion doesn't take into account a significant event that took place in June. We now know the June meeting on Orange book was laser focused on the NCE open issue and Amarin has gone on record that the meeting was proactive. Now, most have had a chance to review the bios of the attorneys present from two law firms. These were the " heavy weights" of NCE exclusivity. And on the FDA side, we they also had top legal counsel present. So what do you think was discussed "proactively" ?
It wasn't the weather.... With billions at stake, Amarin spared no expense to present their perspective why Vascepa deserved NCE status and did so citing case law, prior approvals by FDA and expectation that Amarin be treated similarly as others that received NCE status for similar situations. In summary, it is my opinion that Amarin shot a cannon across the bow and made it clear that there was ample precedent to support litigation should they not receive NCE.
You don't bring big guns to the shoot out, unless you intend to use them - in this case the message was made very clear. "We deserve NCE, and we expect the FDA to grant it"
my expectation is that Amarin's Attorneys left the FDA meeting having made some strong points and giving the FDA legal team an opportunity to "proactively" advise the NCE committee on their responsibility to be BOTH technically correct but also to avoid being partial to one company or another.
This was why the June meeting was made to happen. It was to push the needle from 50% coin toss to 75% or higher
Ignoring this event, who was in attendance and the fact Amarin controlled the agenda and content presented is not prudent nor complete analysis.
Without this meeting, I would agree its 50/50
But Amarin is not about to let "chance" control their future. They essentially "guided" the FDA has to how to avoid being blantanly partial .
In my mind, not taking this event into account is ignoring reality... It did take place, it was proactive, it was about NCE and their representation was led by industry's foremost NCE Attorneys
50/50 ? Hardly.......
I am predicting NCE, the FDA has nothing to gain and everything to lose by not giving NCE status
Almost a no brainer Mark this post
NCE is being portrayed as a win or loose proposition. AMRN will still get 3 yrs exclusivity. If generics file a challenge immediately, so what? AMRN will spend a few millions and the patents till 2030 will come handy in the court. I agree with Jason, NCE may chip away a few $$ from share price but doesn't prevent BP from evaluating this company long-term for buyout for partnership.
It's a very interesting question actually. Unfortunately there is no correct answer to be found speculating. This is a Law/Science decision that can be decided on something as frivolously-seeming as plain language. Pros for NCE are AMRN has a talented legal team, funny enough the Lovaza label actually says that it's pharmacological effects are not understood, name of the active ingredients are clearly differentiated, I think that in the spirit of Hatch/Waxman the FDA will want to grant market exclusivity, there is no market exclusivity left on Lovaza so the FDA simply needs to navigate the precedence issues, which based upon the lack of a specified active moiety in Lovaza, differential clinical data for the specific moiety in amr101 makes granting of NCE low risk considering any future legal proceedings looking for precedent in this case would be narrowly limited to these very specific circumstances.
DHA and EPA are two completely separate compounds. Organic structure different, molecular weight, and CAS numbers are also different. Lovaza does not specifically state the active moiety because they didn't know, they do know thanks to Amarin and the several patents that they will have very soon. They already have it patented out to 2030.
active moiety in Lovasa listed in Orange book: Ethyl Esters
active moiety in Vascepa: EPA (3 SPA studies, two patents, 5 pending patents with reasons for allowance)
Disclosure: Long (more than 10x your previous position), I took A LOT of organic, physiology, pharmacology and have practiced 17 yrs...BFD
Next time provide links
Brandon and Williams
Great to read posts from both of you --informed discussion -much appreciated .
Please provide links if possible .
Williams --Lovonox ? which page is that in your GSK link --didn't see it in a quick browse.
My own view ---CEO has stated several times that if Amarin did not get and NCE it would be a first for any co. required to do an outcome study. He has also stated in the recent CC that it was less important as long as the patents came thru ( words to that effect )
Because no on thinks this is a clear cut case --Brandon --you say 70 /30 , Invest says 50/50 others say 20/80 ( 80% granted ) --the FDA may have some leeway in interpretation.
While many --Sarath for example --see the FDA as purely a Regulator , I see them as more then that . I believe they incentivise company's to take certain actions .
Filing for the Anchor indication for example --if they were purely a regulator , why require the Reduce it trial to be substantually underway before allowing them to file .
The drug is safe and effect --as regulators that is there primary concern --why require an out come trial to be substantually underway.
So I lean more to approval of NCE as likely outcome .
There are no other FDA approved drugs containing EPA aside from Vascepa and Lovaza. There is DHA in prenatal vitamins. I tried an orange book search using Prenate DHA as a trade name formulation to check it's NCE status, but it resulted in no matches. Omega-3 is not produced by fish, but obtained from them since they feed on algae (the source).
I do acknowledge there are pro-NCE cases for AMRN in that the FDA required non-clinical and clinical studies characteristic of requirements of a NCE drug, the FDA currently seems to characterize them as different class names (omega-3-acid ethyl esters vs icosapent ethyl even though icosapent ethyl is in omega-3-acid ethyl esters) and is requiring REDUCE-IT which would be unusual if not granted NCE. However, should REDUCE-IT show positive outcomes, additional patents could be filed for the indication and extend patent life.
I still believe one cannot ignore insider sales prior to NCE and patent announcements. There was significant amount of money to be made off these sales and significant shares/options dumped. I do not believe a buyout talk will reach fruition until more is known regarding NCE/patents. Why sell when there are so many more positive catalysts in NCE/patents/Anchor/mixed dyslipidemia label?
If I had to place a bet, I'd say I'm betting 30% chance NCE 70% against it.
Disclosure: I sold 5,000 shares in after hours 7/30/12 when insider sales were announced. I currently hold zero shares, but am considering a smaller position should the risk-reward become an attractive trade within the next week. I was a chemistry major in college, hold a doctor of pharmacy degree and have 10 years of pharmacy practice experience. "
Great post. You have a very convincing argument for why NCE will not be granted.
However, I think you missed 1 point. It's a very subtle one. The definition of active moiety. In Lovaza, the active moiety is the combination of EPA and DHA. It is precisely the combination that exhibits the pharmacological behavior of Lavaza. Therefore, the active moiety is EPA+DHA and you can't divide them into 2 active moiety. IN Vascepa, the active moiety is EPA, and nothing else. EPA+DHA <> EPA. Since Lovaza'a ctive moiety is undivided EPA+DHA, you can't say EPA has been approved in COMBINATION. Let me give you an example of active moiety in COMBINATION: VVUS's Qsymia, it's p-h-e-n+Topamax, each is an active moiety and is responsible for certain pharmacological effects of Qsymia, i.e., p-h-e-n: appetite suppression and Topomax: metabolism enhancer. Do you see the difference now?
Anyways, that's my view and I believe NCE is 90%.