Oh this story just gets better and better

CDER director Janet Woodcocks set's TEVA straight. Too bad she didn't have the same consideration for Vascepa's NDA.

http://www.regulations.gov/#!documentDetail;D=FDA-2013-P-0025-0003

The drug in question was already approved in a mix, prior to it's MS approval.

Biogen Idec received NCE for Dimethyl Fumarate, after it's 505B1 application was approved. Like Icosapent Ethyl, Dimethyl Fumarate was previously approved as a "mix" in Novartis's Aliskiren Hemifumarte. The following links lead to the approvals and Pubchem sites clearly showing the compounds. I can find no FDA delay's or confusion regarding the approval of and designation of NCE for Dimethyl Fumarate.

Dimethyl Fumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=204063&Product_No=001&table1=OB_Rx

Dimethyl Fumarate's chemical structure can be viewed here:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=637568&loc=ec_rcs
Aliskiren Hemifumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=022217&Product_No=001&table1=OB_Rx

The mix containing Biogen's Dimethyl Fumarate can be viewed here at PubChem under Novartis's Aliskiren Hemifumarate:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9939627&loc=ec_rcs



Vascepa and Dimethyl Fumarate share the same mix/NCE parodox:
As GSK has recently stated in the response to Crowell & Moring LLP- CP (FDA-2013-P-0148-0001), "the active ingredient (In Lovaza) is not simply the seven omega-3-acid ethyl esters, but the entire mixture", the Icosapent Ethyl should be considered a single agent separate from the mixture. Clearly CDER came to this conclusion with Biogen's Dimethyl Fumarate.
http://www.regulations.gov/#!documentDetail;D=FDA-2013-P-0148-0003

Dr. Woodcock your words will come back to haunt you...LOL!!!

http://www.regulations.gov/#!documentDetail;D=FDA-2013-P-0025-0003

Read pages 5 and 6, Janet explains how the FDA does it...

Background:
-Vascepa has no exclusivity after a year
-NDA letter had no reason why an Ad Com wasn't required
-The drug this letter is refering to is a mix that's already been approved before.

Must Read and then laugh.... a lot!

Williams

Looks like GSK, AZN, & AMRN on call on 13th

Both GSK & AZN got MS downgrades next day, AMRN upgrade

No Merck or Pfizer

GSK (GSK downgraded)
http://www.theflyonthewall.com/permalinks/entry.php/AAPL;GSK;BAC;MSid1860671/AAPL;GSK;BAC;MS-On-the-Fly-Periodicals-WrapUp?symbol=GSK
AZN & AMRN (AZN downgrade next day by MS, Amarin upgraded)
http://www.theflyonthewall.com/permalinks/entry.php/AZN;AMRN;FRXid1620807/AZN;AMRN;FRX-AstraZeneca-looking-at-for-possible-takeover-candidates-Bloomberg-says?symbol=AMRN;AZN


Merck (no downgrade by MS)
http://www.theflyonthewall.com/permalinks/entry.php/AGN;ONXX;MRKid1859847/AGN;ONXX;MRK-Analyst-says-Merck-could-look-to-buy-Allergan-or-Onyx?symbol=MRK
Pfizer (13 th not moving forward with ONXX bid)

http://www.theflyonthewall.com/permalinks/entry.php/PFEid1866184/PFE-Pfizers-Wyeth-pays-M-to-settle-Rapamune-marketing-charges?symbol=PFE

-------
Forest labs and Cubist met earlier....to discuss antibx.

Conference call between AZN and Amarin on 8-13...may have spiked the volume, also received PR from Amarin.

August 13, 2013
Amarin to Present at the Canaccord Genuity 33rd Annual Growth Conference



10:32 EDT 8-13-2013 AMRN, AZN Cowen's pharmaceutical analysts hold an analyst/industry conference call
Subscribe for More Information http://www.theflyonthewall.com/permalinks/entry.php/OME;AMRN;OMTH;AZNid1838690/OME;AMRN;OMTH;AZN-Fish-oil-product-makers-mixed-after-Omthera-acquired?symbol=AMRN;AZN

AZN also got downgraded to by Morgan Stanley---perhaps AZN's planning on spending a lot of money

11:55 EDT AZN AstraZeneca downgraded to Underweight from Equal Weight at Morgan Stanley
Subscribe for More Information


--------------------

There's a serious IP Epanova tussle going down at the USPTO and AZN is getting their Azz's handed to them.

I'd like to point out Amarin got a 4 PM after market close slot.

GSK to Pay $185M in Flonase Antitrust Class Action Settlements
June 21 2013

New York, NY: Two settlements have been approved in the antitrust class action lawsuits pending against GlaxoSmithKline PLC, (GSK). The lawsuits allege that GSK deliberately prevented generic versions of Flonase nasal spray from going to market.

The settlements total $185 million, with $150 million designated for reimbursement to people and entities in the US who purchased Flonase directly from GSK at any time from May 19, 2004 until March 6, 2006. For complete information on this settlement, and to download forms, visit flonasedirectsettlement.com The case is, In re Flonase Antitrust Litigation, No. 08-CV-3149, is pending in the United States District Court for the Eastern District of Pennsylvania.

A second class involving those who indirectly purchased Flonase and generic Flonase – will receive reimbursement from a $35 million settlement fund. These class members include anyone who purchased Flonase or generic Flonase for personal, family or household consumption in the United States and its territories from May 18, 2004 through March 31, 2009. Also included in the class is anyone who made co-payments or other partial out-of-pocket payments through their health plans. For complete information on this settlement visit flonasesettlement.com The case is In re Flonase Antitrust Litigation, Case No. 8-cv-3301 and Medical Mutual of Ohio v. GSK, Case No. 12-cv-4212 in the Eastern District of Pennsylvania.

GSK to Pay $185M in Flonase Antitrust Class Action Settlements
June 21 2013

17382s.png New York, NY: Two settlements have been approved in the antitrust class action lawsuits pending against GlaxoSmithKline PLC, (GSK). The lawsuits allege that GSK deliberately prevented generic versions of Flonase nasal spray from going to market.

The settlements total $185 million, with $150 million designated for reimbursement to people and entities in the US who purchased Flonase directly from GSK at any time from May 19, 2004 until March 6, 2006. For complete information on this settlement, and to download forms, visit flonasedirectsettlement.com The case is, In re Flonase Antitrust Litigation, No. 08-CV-3149, is pending in the United States District Court for the Eastern District of Pennsylvania.

A second class involving those who indirectly purchased Flonase and generic Flonase – will receive reimbursement from a $35 million settlement fund. These class members include anyone who purchased Flonase or generic Flonase for personal, family or household consumption in the United States and its territories from May 18, 2004 through March 31, 2009. Also included in the class is anyone who made co-payments or other partial out-of-pocket payments through their health plans. For complete information on this settlement visit flonasesettlement.com The case is In re Flonase Antitrust Litigation, Case No. 8-cv-3301 and Medical Mutual of Ohio v. GSK, Case No. 12-cv-4212 in the Eastern District of Pennsylvania.

Legal Help

That's very interesting.

Dew

Follow this:

If Crowell & Morning CP was filed by BP...doesn't matter which one.

And the FDA delayed exclusivity partly because of CP or identifiable outside BP influence not only is this against policy it's collusion.

Those involved could be charged if:

" The Noerr- Pennington doctrine generally immunizes efforts to petition the government from antitrust liability. The doctrine is based on the premise that parties should be able to exercise their First Amendment right to petition the government without penalty. However, not all conduct is immunized under the doctrine.
While petitioning is generally protected, a party is not entitled to Noerr-Pennington immunity where the petitioning activity “ostensibly directed toward influencing governmental action [ ] is a mere sham to cover ... an attempt to interfere directly with the business relationships of a competitor....” Noerr, 366 U.S. at 144. In other words, when the sole goal of petitioning is to interfere with the business of one’s rival, it is not protected. To prove that the petitioning is a sham, a plaintiff must demonstrate that it is both objectively and subjectively baseless."

Filing a CP to delay Amarin's exclusivity directly interfered with their business model of selling the company. If a rival interfered in this process, Noerr-Pennington won't save the CP filer or the FDA from accepting a CP to delay.

Next:

Who filed the CP? Also, ascertain "motive" for filing. Any competitor that filed, had motive to delay.

Did the FDA delay exclusivity further? CP was hand delivered and filed by a former FDA attorney, who was an employee a short year ago. Timing was two weeks to the date before a MAPP likely assisting in Vascepa being defined as a separate NCE form Lovaza's ethyl ester mix.

The FDA is full of paperwork and email trails both of these questions could be answered quickly.

If X-BP is proven to have filed a CP to delay exclusivity, and the FDA colluded with this BP by accepting a CP with clear conflict of interest, violating CP acceptance policy, and violating a CP from the completion of a 505 application for reasons other than public safety. Proceeding with an Antitrust Law suit against CP filer would be foreseeable.

X-BP would be liable, the FDA would just get dragged through the mud....again.

If GSK filed the original CP through Crowell & Morning, and then used a different law firm to comment to their own CP....they are totally F'd. That would be the easiest "sham" to prove and they would have no protection under Noerr-Pennington immunity.

Dew your message got deleted...why?

Do you follow? Anyone have comments on the argument?

STS
Could very well be the same player with the first ARNA Ad Com crying rat cancer....Dr. Eric Coleman signed our NDA for Vascepa. I also was in intimate contact with the FDA through the second Ad Com for ARNA...check my yahoo posting history.

March 2011 FDA admitted they didn't know if they'd consider Vascepa a NCE...this is more than a delay and I didn't get agressive until they Lovaza CP.

Yes I caused this delay....LOL..."I hindered the process", what...the process of retaliation?

This decision is overdue, I'm done waiting. I fully expect a tax audit this year too;)

Williams

Link? The complaint will be filed through me, Mr. Tax payer.

Baaaaaa
Timing...

He was employed by the FDA less than a year before petition filed. The CP was hand delivered to the FDA two weeks before MAPP 5021 was posted....kinda of suspicious...but when it comes to the FDA I'm very paranoid.

Williams

JL---not a great story but all I have time for.

If the CP was filed by an Amarin competitor and the FDA delayed exclusivity for the decision...Amarin has good cause to make an allegation.

http://www.wsgr.com/publications/PDFSearch/silber0112.pdf

-------------------
First, I've had numerous emails with CDER Ombudsman, Virgina Behr and two phone conversions all related to NCE delay. Ms. Behr also put me in touch with a CDER official I will not name at this time. After a brief search on this individuals background she appeared to have contact with GSK's Marketing Director. I confronted her on this connection and she stammered around it....and then gave me the Amarin stonewall, "a decision regarding exclusivity for Vascepa is still under review".

At this point I decided to make a formal complaint, and notified Ms. Behr....

In a very round about way, I will not get into, I was put in touch with a Senate Judicial Investigator.

This is a copy of my last e-mail with Ms. Behr, it was also CC'd to the CDER contact that appeared to "know" GSK's Marketing Director:

Williams,

Thanks for letting me know.

Virginia

From: Williams (changed)
Sent: Thursday, August 01, 2013 11:51 AM
To: Behr, Virginia L; Khatri, (unnamed CDER contact)
Subject: Formal Investigation Request

Ms. Behr

August 19 th 2013 I will request a formal investigation by Investigative Counsel Senate Judiciary Committee into the exclusivity delay for Vascepa based on Lovaza Citizen Petition Suspect Timing" and source of filing.

Under section 505(q)(1)(B) a 502(b)(2) -application can be delay only due for safety reasons
-the FDA is required to provide to the applicant not later than 30 days after making the determination: 1) that a determination to delay has been made 2) request additional information from the applicant 3) brief summary of issues

The CP is unrelated to public safety and filed by a competitor of Amarin Pharmaceuticals. Under 505(q)(1)(B), the CP should not have delayed the completion of Amarin's 505(B)(2) 5 yr exclusivity request.

In addition, an application filed by a competitor and former FDA Attorney intended to delay exclusivity, should be rejected outright by the FDA.

Thank You,

Williams


I also sent an email to the FDA Ombudsman to express my concerns of CDER's retalitory behaviors, Ms. Behr suggested this in our last phone conversation:



Attention: Laurie Lenkel, Virgina Behr, Janet Woodcock, M.D., Margaret A. Hamburg, M.D., Kati Johnson, & CDER exclusivity Board
-Retaliation Policy
At the FDA, our mission is to protect, promote, and enhance the public health. We also have important responsibilities to the industries we regulate, including working to bring new products to the market and minimizing regulatory burdens.

In carrying out this mission, FDA employees are required to make many decisions and take many actions involving complex clinical, scientific, legal, and factual issues. In this context, questions can be, and have been, raised about the fairness of agency proceedings and retaliatory actions-against companies which challenge or criticize the agency.

We take such concerns and allegations very seriously. Without question, companies are free to vigorously challenge agency positions and requirements, and to freely voice their views to the agency, the press, the public, and the Congress. One of our fundamental duties is to be scrupulously fair, even-handed and objective. We can accept no less. Fear of retaliation among those we regulate may chill scientific, legal and policy discourse, depriving the agency of information crucial to sound judgments and decisions. Given our special responsibilities, all FDA employees must make every effort to avoid even the appearance of unfairness or retaliatory action.

Because of the critical importance of these issues, any allegation of retaliation should be reported immediately to the Office of the Ombudsman. In addition, anyone with concerns about retaliation or related issues should contact that office. Such matters will be treated in confidence, and the office will work with other agency offices to address all relevant issues.



Ms. Lenkel,
I have exchanged many e-mails and have had two phone conversations with Ms. Behr, she suggested I forward you my concerns regarding CDER's exclusivity delay for Amarin's Vascepa.


It's my opinion CDER played Regulatory Favoritism with the respect to Amarin's Vascepa/Icosapent Ethyl application exclusivity delay. I also allege CDER has retaliated against Amarin investors and Amarin Pharmaceuticals by further delaying the decision after complaints to CDER were communicated. Also delays may have been extended by the acceptance of a Citizen Petition, with likely conflict of interests. Citizen Petition FDA-2013-P-0148-0001 drafted by and ex-FDA Attorney now a partner at Crowell & Moring LLP. I also fear CDER will retaliate against Amarin for current sNDA and future NDA after formal complaints have been made to the Senate Judiciary Committee Investigators, which is my intention after another delay. I request Ms. Laurie Lenkel and Ms. Virgina Behr closely follow the current review of Vascepa's sNDA to assure fairness in this process.


History of Amarin's Vascepa/Icosapent review:
Icosapent Ethyl was approved for the treatment of very high triglycerides on July 26, 2012. Vascepa is Amarin's only approved product and at this time Amarin's revenue stream was Amarin stock holders. Upon approval, neither NME or NCE was applied to Vascepa by CDER for undisclosed reasons. Amarin and Amarin shareholders clearly communicated to CDER that an exclusivity decision was paramount to Amarin's business plan. After 12 consecutive delays Amarin's Market Value has collapse from $2.4 Billion to $820 Million, and Amarin was forced to take out a very high stakes loan leveraging all it's IP on default. Today, after 13 Months CDER was failed to rule on a very strait forward decision. The continued delay is perceived as punitive.




Example of Regulatory Favoritism:
Biogen Idec received NCE for Dimethyl Fumarate, after it's 505B1 application was approved. Like Icosapent Ethyl, Dimethyl Fumarate was previously approved as a "mix" in Novartis's Aliskiren Hemifumarte. The following links lead to the approvals and Pubchem sites clearly showing the compounds. I can find no FDA delay's or confusion regarding the approval of and designation of NCE for Dimethyl Fumarate.

Dimethyl Fumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=204063&Product_No=001&table1=OB_Rx

Dimethyl Fumarate's chemical structure can be viewed here:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=637568&loc=ec_rcs
Aliskiren Hemifumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=022217&Product_No=001&table1=OB_Rx

The mix containing Biogen's Dimethyl Fumarate can be viewed here at PubChem under Novartis's Aliskiren Hemifumarate:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9939627&loc=ec_rcs



Vascepa and Dimethyl Fumarate share the same mix/NCE parodox:
As GSK has recently stated in the response to Crowell & Moring LLP- CP (FDA-2013-P-0148-0001), "the active ingredient (In Lovaza) is not simply the seven omega-3-acid ethyl esters, but the entire mixture", the Icosapent Ethyl should be considered a single agent separate from the mixture. Clearly CDER came to this conclusion with Biogen's Dimethyl Fumarate.
http://www.regulations.gov/#!documentDetail;D=FDA-2013-P-0148-0003

Dr. Goldenberg came to this very conclusion in a fall of 2012 Pharmaceutical Approval Update . "The active moiety in GlaxoSmithKline’s Lovaza, a similar agent for the treatment of hypertriglyceridemia, is a mixture of omega-3-acid ethyl esters that includes icosapent ethyl (EPA), docosahexaenoic acid (DHA), and a few others. Without requiring GlaxoSmithKline to specify which ester helps to lower triglycerides, the FDA considered the mixture of EPA and DHA as the active moiety that is responsible for the physiological and pharmacological action of Lovaza. Vascepa might have an advantage over Lovaza; it does not increase LDL-C levels, which has sometimes been observed with Lovaza.

The FDA considers Vascepa to be a new chemical entity. It contains only EPA but not DHA, and it does not contain any appended portions of both EPA and DHA that cause them to be an ester, salt, or other non-covalent derivative. Therefore, its active moiety has not been previously approved by the FDA in any other application submitted under Section 505(b) of the Federal Food, Drug, and Cosmetic Act."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462608/




Resolution:


CDER immediatly contact Amarin and inform them of a decision and when the OB will be updated. Please forward my request to Dr. Hamburg as she's ultimatly responsible for the actions of CDER.


Respectfully,

Williams

---------------------------------------


At this point, my goal is for Amarin to get a fair Anchor review. In my opinion this may not happen with the current CDER administration.

Crazy Azz Retail Investor,
Williams/BioBill

Sorry JL... I didn't have time to write a novel. I hope my above rant to Chobix clears it. I know you hate my rants and speculation, I'm obviously upset the FDA is so corrupt.
WILLIAMS

Choubix

The email excerpts are from the review documents posted March 6th 2013. Skip the boring Regulation paper work and start reading page 33.

http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000AdminCorres.pdf

The FDA is certainly "cheesed off", the Medical review contains quotes of them bitching about Amarin including the Anchor study.

To understand my "speculation", in a perfect regulatory world:
1) A company files a 505(b)2 and requests 5 years of NCE status
2) The FDA accepts the application and decides on whether or not it needs an Ad Com (outside professional advice on the review, it's not always needed)

A. An Ad Com is scheduled, FDA decides to approve (with or without a positive Ad Com) NCE is granted
B. The FDA decides no Ad Com is needed, no safety of efficasy questions that the FDA needs an outside opinion on. However, to grant NCE status the FDA needs to provide a simple statement as to why no Ad Com was need in the approval letter to fullfill the 505 regulations to grant NCE status.

In the above perfect world, Amarin's Marine review followed path "B". To be granted NCE NO statement was made in the final approval letter as to why an Ad Com was not required. So from March 2011 the FDA couldn't come to a conclusion what GSK so nicely summed up in their CP comment letter:

"As this discussion shows, the Citizen Petition’s argument that Lovaza’s strength improperly describes “the overall weight of an individual capsule, including excipients” is not correct.32 Lovaza’s strength is based on its active ingredient, the naturally-sourced mixture, and is not based on any “capsule properties,” such as excipients or inactive ingredients.33 The Citizen Petition’s argument reflects a misunderstanding of the unique character of naturally derived products. As FDA has explained, these are inherently “more complex and 34 heterogeneous than the purified new molecular entity classically approved by FDA.”
drug is developed essentially from the “bottom up.” The drug is isolated and tested for safety and efficacy, and inactive ingredients are added for stability, appearance, and other purposes. For such a product, the API is completely characterized, and therefore the strength is easily determined. However, naturally-derived drug substances are developed essentially from the “top down.” The drug is extracted from natural sources, such as plants or fish, and then subject to a purification process."
http://www.regulations.gov/contentStreamer?objectId=0900006481391626&disposition=attachment&contentType=pdf

In the Fall of 2012, the FDA communicated to Amarin "the letter" for the above "B" was circulating the FDA. It has yet to materialize after many many months. Amarin needs either that letter/paragraph in the original Marine approval letter or an Ad Com to fulfill 505 regs to get NCE.

However, for the very same reasons Marine didn't need an Ad Com: 1) no safety issues 2) met all primary and secondary end points at 4 gram dose, Anchor doesn't need an Ad Com either. How the FDA is going to convince a clinician to take a vacation to get paid 1/4 to discuss NOTHING is ridiculous...and a waste of time and money. The Ad Com calendar is starting to be filled beyond Amarin's October 16 schedule, the Anchor Ad Com is not officially on the books yet, and won't be needed if this "letter" get's signed.

I think "the letter" will materialize, signed by Margaret A. Hamburg, Vascepa will get NCE and the FDA will cancel Anchor Ad Com.

The FDA has 2 more updates to play this "game", however, Monday a Judical Senate Comittee investigaton will be initiated into CDER for Regulatory Favoritism, CDER Retailation, and potential Antitrust allegations.

Cheers

Williams

The "letter" is circulating....not everyone has agreed to sign it... Those people will have the most to explain when the dust settles.

So, the FDA can't agree on "wording" so we get an Ad Com Comittee to fulfill the regulatory BS of the 505. Note a date for the Ad Com has not been published in CDER calendar. Goal...was Oct 16.... No Ad Com in books though. Scheduling an Ad Com for Anchor was a ploy to get "wording" correct on Marine NCE approval. Live and learn;)

Why the FDA is jacking us around with NCE:

Amarin irritated the FDA, the delay is back lash and retaliation for not playing the game right. March 16 th 2011, over two years ago "A final decision on whether AMR101 is a new chemical entity has not been made"

Regulatory Retaliation, Abuse of Power, ... The list is long...


Friday, September 30, 2011 11:26 AM
To: Johnson, Kati
Subject: NDA 202057 - additional follow up Importance: High
Hi Kati,
I’m sure that you don’t want to hear from me today – but, I have been asked to do an additional follow up with you before you go on vacation. We had a call with our Board last night and everyone still believes that we are a 505(b)(1). However, they are a little freaked out about not having the possibility to amend the application to be
a 505(b)(2) in the event that the FDA disagrees with us at day 45. All of the regulatory lawyers and other regulatory advisors who we have consulted with say that the FDA, as a general standard practice, allows the company to amend the NDA prior to issuing a RTF if the change can be made quickly – like 24 hours. As a small company, we can’t survive having a RTF because it could put us out of business. So that’s what they are having more struggle now than before is that it sounds like we won’t have that opportunity here. Can you confirm for me that this is the case? Or, is there someone else that I could or should discuss this with while you’re out? Thanks again for all of your help with this – I really do appreciate it!
Peggy


-------
Post-Meeting Discussion- The study populations, inclusion and exclusion criteria as well as the different indications of the ANCHOR and the MARINE trials preclude the integration of the efficacy data from the trials. Thus your offer to include efficacy data from the ANCHOR study is not accepted as part of the Integrated Summary of Efficacy for the indication “as an adjunct to diet to reduce triglyceride levels in adult patients with very high > 500 mg/dL triglyceride levels

-------

RA-2 Based upon the results of the MARINE clinical study and the factors set forth in section III.A.1 of the FDA’s August 2008 Guidance on Convening Advisory Committee Meetings, AMR101 is not likely to be referred for Advisory Committee review. Does the FDA agree?
FDA Preliminary Response: Under 505(s) of the FD&C Act, all new chemical entities must either be discussed at an Advisory Committee Meeting or a justification provided as to why it will not be discussed. A final decision on whether AMR101 is a new chemical entity has not been made.
Meeting Discussion: The firm pressed for a more definitive response given the limited resources of the company. The sponsor was informed that, based on what is known about the compound at this time, and in our opinion it was less likely that AMR101 would go to an Advisory Committee. Final decision on the question of an Advisory Committee would be made after submission of the NDA


Williams

A little twist. Amarin originally used a 505b1 for Marine and changed to a 505b2 after not having original pharmaceudical info.

Amarin was assured they could still apply for 5 yrs of NCE...this is in an email under the review section.

We don't know what form Amarin used for the sNDA.

This might be significant in the NCE timing.

I'm trying to clarify this with Amarin today.

Random exclusivity thoughts:

Amarin first filed Marine under a 505b1 application and HAD to change to 505b2 because they relied on outside data. It may be possible for them to file a 505b1 for Anchor and completely reset the exclusivity clock.

If this is the case, I'll have to send the FDA flowers and an apology card....

The only way the FDA could possibly makeup for the damage they caused to Amarin and shareholders is to approve Anchor early, grant NCE, and permit a sNDA for REDUCE-IT immediately..

There's no Ad Com date set on the FDA calendar...if you were a clinician would you take a day off to discuss something so F'kn obvious.

Agree, I've found no connection with Anchor and NCE. I know it's stated about an Ad Com and NCE but that's quite irrelevant when an Ad Com isn't required. Under Marine's Chemical review, Icosapent Ethyl was a Chemical Type 1, reserved for a NME. Up to 7-25-2013...this was the case ...then the FDA delayed the decision when Kati Johnson and Eric Coleman didn't finish the form .

Agreed. ATP 4 guidelines are complete and are awaiting HHS clearance FYI....

The US Department of Health and Human Services provides editorial review, comment, and approval.

Patent 8415345 is GSK melanoma drug, wasn't this patent number assigned to Amarin's 13/349/157

I keep double checking the numbers but can't find an error.

I also can't find a list of claims for Amarin's '157 that supports Marine.

http://www.drugpatentwatch.com/ultimate/preview/patent/8415345

What's going on here?

Yoyo

United States Patent 8,415,345

Application number 13/349/157 was assigned patent number 8415345 correct?

But this is a search for 8415345:

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=8415345&OS=8415345&RS=8415345

It's a GSK patent issued 4-9-2013.

What am I missing here?

13768869 also receive NOA
Claim
#1"a pharmaceutical composition comprising about 2500 mg to about 5000 mg of ethyl Eicosapentaenoate and not more than 5% of Docosahexaenoic acid or it's esters, by weight of all fatty acids."

This pharmaceutical composition covers about 100 mg of DHA fatty acid.


25% of 2 gram dose of Epanova is 500 mg of DHA fatty acid
15% of 2 gram dose of Epanova is 300 mg of DHA fatty acid




"Epanova contains EPA and DHA in their free fatty acid form at a total concentration of 50-60% EPA and 15-25% DHA along with other potentially active omega-3 fatty acids stored in a patent-protected capsule with a patent-protected coating designed to maximize bioavailability and tolerability. Free fatty acids are the chemical form in which essential fatty acids, such as EPA and DHA, are absorbed in the digestive tract. The active ingredient of Epanova is a complex mixture of concentrated omega-3 free fatty acids purified from crude marine fish oil and are, therefore, of natural origin. Our strategy is to initially develop and commercialize Epanova in the United States as a prescription monotherapy as an adjunct to low-fat diet in patients for the reduction of triglyceride levels greater than or equal to 500 mg/dL, or severe hypertriglyceridemia."

http://www.omthera.com/epanova_overview.html

Wow! Everyone missed a big NOA last week!
'897's claims changed to 2500 to 5 mg EPA in Fatty acid or Ethyl ester form for the treatment of Trigs

Reasons for allowance 8-7 and document Varification 8-10

This patent covers any Omega 3 composition with > 2500 mg of EPA in Fatty Acid or Ethyl Ester form. IE. Epanova is limited to less than 2.5 grams.

13768897

Williams

Certainly not trying to be "hostile"....."MO, there was no Adcom for Marine because A) was not for new indication, and B) the FDA did not consider Vascepa a NCE. This is Not MY belief, just what I think happened. "

A drug approval is about 3 things:
1) Medical need
2) Safety
3) Efficacy

If you have a drug that's safe and works great, but it cures the Martian flu pox.... Should the FDA waste time to regulate it....No.

"New Indication" has nothing to do with NCE. It's happens to be what Amarin stated was the belief for the Ad Com. Ad Com's are to determine safety and efficacy....period. The only two legitimate questions are does Vascepa statistically lower lipids and does the Anchor data support this? Is Vascepa safe for people to take? Does it cause an increase in prostate cancer is even legitimate. Is it a NCE is a policy decision, not Ad Com.

The FDA could bring in experts to discuss whether the treatment of high triglycerides are necessary. It's would be my number on concern if I was prepping for Ad Com.

--------------
Back to NCE:

The FDA listed Amarin's original 505b1 application as a Chemical Type 1 which is a NME. It was left blank after Amarin changed the 505b1 to a 505b2 when they discovered the had to use Mochida Pharma data on Epadel. Amarin expressed concern about still being able to file for 5 yr exclusivity and they where assured no problem....Some bureaucratic SNAFU ensued and here we are 13 months later. These are facts that can be ascertained through read Amarin's review documents. Amarin did F up the process, and the FDA got pissy. In the mix of all the hype and complaints the FDA purposely delayed exclusively further.

Just my take on studying this BS for the last 16 months.

"You don't want to tick these guys off." I Do! Further delays only solidifies my point of Regulatory Favoritism, and Retaliation...both are very serious allegations that MUST be investigated.

Williams

CDER documented in Icosapent Ethyl's Marine review no Ad Com was needed due to NO safety concerns.

http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/ucm079940.pdf

This doesn't excuse a 13 month delay, especially since it's document in the NDA review.

Any other lame AZZ excuses for the FDA?

Williams

AdCom has nothing to do with NCE...AdComs are to debate risk/reward period. Does it cause cancer? No Does it save lives? Don't know yet. Does it improve lab values? Yes. Does it have horrible side effects? No

This Ad Com is a BS stall job...!!! Risk/Reward side effect profile is the best ever of any drug.

Yes

LM, don't hurt your brain on the chemistry...Dr. Goldenberg covers it here:
"The FDA considers Vascepa to be a new chemical entity. It contains only EPA but not DHA, and it does not contain any appended portions of both EPA and DHA that cause them to be an ester, salt, or other non-covalent derivative. Therefore, its active moiety has not been previously approved by the FDA in any other application submitted under Section 505(b) of the Federal Food, Drug, and Cosmetic Act."

If you have a mix of chemicals in a drug, and you pull one out that leaves the others chemically unchanged, you have a NCE. The mix of Omega's is less complex chemically for the FDA. If Biogen had Icosapent Ethyl they'd have a NCE designation....that's the point.

If I don't hear back from Margaret Hamburg next week, this is going to the Senate Judicial Committee.

Ajax--This is the same argument, but the FDA has dragged ass on Vascepa. Where are you getting the two weeks before PDUFA?

Read this:

Please read and comment, It's a portion of my FDA complaint:


Biogen Idec received NCE for Dimethyl Fumarate, after it's 505B1 application was approved. Like Icosapent Ethyl, Dimethyl Fumarate was previously approved as a "mix" in Novartis's Aliskiren Hemifumarte. The following links lead to the approvals and Pubchem sites clearly showing the compounds. I can find no FDA delay's or confusion regarding the approval of and designation of NCE for Dimethyl Fumarate.

Dimethyl Fumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=204063&Product_No=001&table1=OB_Rx

Dimethyl Fumarate's chemical structure can be viewed here:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=637568&loc=ec_rcs
Aliskiren Hemifumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=022217&Product_No=001&table1=OB_Rx

The mix containing Biogen's Dimethyl Fumarate can be viewed here at PubChem under Novartis's Aliskiren Hemifumarate:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9939627&loc=ec_rcs



Vascepa and Dimethyl Fumarate share the same mix/NCE parodox:
As GSK has recently stated in the response to Crowell & Moring LLP- CP (FDA-2013-P-0148-0001), "the active ingredient (In Lovaza) is not simply the seven omega-3-acid ethyl esters, but the entire mixture", the Icosapent Ethyl should be considered a single agent separate from the mixture. Clearly CDER came to this conclusion with Biogen's Dimethyl Fumarate.
http://www.regulations.gov/#!documentDetail;D=FDA-2013-P-0148-0003

Dr. Goldenberg came to this very conclusion in a fall of 2012 Pharmaceutical Approval Update . "The active moiety in GlaxoSmithKline’s Lovaza, a similar agent for the treatment of hypertriglyceridemia, is a mixture of omega-3-acid ethyl esters that includes icosapent ethyl (EPA), docosahexaenoic acid (DHA), and a few others. Without requiring GlaxoSmithKline to specify which ester helps to lower triglycerides, the FDA considered the mixture of EPA and DHA as the active moiety that is responsible for the physiological and pharmacological action of Lovaza. Vascepa might have an advantage over Lovaza; it does not increase LDL-C levels, which has sometimes been observed with Lovaza.

The FDA considers Vascepa to be a new chemical entity. It contains only EPA but not DHA, and it does not contain any appended portions of both EPA and DHA that cause them to be an ester, salt, or other non-covalent derivative. Therefore, its active moiety has not been previously approved by the FDA in any other application submitted under Section 505(b) of the Federal Food, Drug, and Cosmetic Act."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462608/

Please read and comment, It's a portion of my FDA complaint:


Biogen Idec received NCE for Dimethyl Fumarate, after it's 505B1 application was approved. Like Icosapent Ethyl, Dimethyl Fumarate was previously approved as a "mix" in Novartis's Aliskiren Hemifumarte. The following links lead to the approvals and Pubchem sites clearly showing the compounds. I can find no FDA delay's or confusion regarding the approval of and designation of NCE for Dimethyl Fumarate.

Dimethyl Fumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=204063&Product_No=001&table1=OB_Rx

Dimethyl Fumarate's chemical structure can be viewed here:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=637568&loc=ec_rcs
Aliskiren Hemifumarate's OB Exclusivity:
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=022217&Product_No=001&table1=OB_Rx

The mix containing Biogen's Dimethyl Fumarate can be viewed here at PubChem under Novartis's Aliskiren Hemifumarate:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9939627&loc=ec_rcs



Vascepa and Dimethyl Fumarate share the same mix/NCE parodox:
As GSK has recently stated in the response to Crowell & Moring LLP- CP (FDA-2013-P-0148-0001), "the active ingredient (In Lovaza) is not simply the seven omega-3-acid ethyl esters, but the entire mixture", the Icosapent Ethyl should be considered a single agent separate from the mixture. Clearly CDER came to this conclusion with Biogen's Dimethyl Fumarate.
http://www.regulations.gov/#!documentDetail;D=FDA-2013-P-0148-0003

Dr. Goldenberg came to this very conclusion in a fall of 2012 Pharmaceutical Approval Update . "The active moiety in GlaxoSmithKline’s Lovaza, a similar agent for the treatment of hypertriglyceridemia, is a mixture of omega-3-acid ethyl esters that includes icosapent ethyl (EPA), docosahexaenoic acid (DHA), and a few others. Without requiring GlaxoSmithKline to specify which ester helps to lower triglycerides, the FDA considered the mixture of EPA and DHA as the active moiety that is responsible for the physiological and pharmacological action of Lovaza. Vascepa might have an advantage over Lovaza; it does not increase LDL-C levels, which has sometimes been observed with Lovaza.

The FDA considers Vascepa to be a new chemical entity. It contains only EPA but not DHA, and it does not contain any appended portions of both EPA and DHA that cause them to be an ester, salt, or other non-covalent derivative. Therefore, its active moiety has not been previously approved by the FDA in any other application submitted under Section 505(b) of the Federal Food, Drug, and Cosmetic Act."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462608/

Yo! Yo, correction of your "correction". Image wrapper file. 8-8-2013 track one request again after Final Rejection.

This is a $260 Million dollar patent....

"Regarding Astra and Omthera. AstraZeneca, you would have to ask those two folks what happened. What we saw was really about a very small $260 million enterprise value of acquisition that was most likely really geared towards Crestor protection rather than triglyceride lowering, but again that's just speculation on our part, but thanks for the question."

"Very small"- JZ's thinking Multibillions

Yes, you are correct. Biogens NCE Dimethyl fumarate is also contained in a previously approved Novartis product.

JL your thoughts?
Update on 13/685,281, Amarin's Epanova-clone Patent:
1) 8-8-2013 filed track one, Trying to speed up approval.
2) Paid $2670.00 to continue examination
3) Paid $2000.00 to track one priority
4) Mehar Manku, PhD. argues the basis of rejection with a signed Affidavid, factualy lays out Opheim "obvious" rejection was incorrect. "I have reviewed the Opheim patent application and nowhere does Pheim disclose compositions containing EPA and DHA in free acid form. Instead, specifically directs that EPA and DHA free acids be REMOVED from it's compostions."

POWERFUL FACT BASED ARGUEMENT

5) Another Affidavid by Paresh Soni, MD PhD
6) Attached study compairing the FFA vs methly esters
7) Updated claims 500 trigs, EPA 70/30 DHA, EPA 80/20 DHA, EPA 90/10 DHA...


I really think Amarin's going to pull this off. AZN would have flat out wasted $260 million if Amarin get's a NOA.

Update on 13/685,281, Amarin's Epanova-clone Patent:
1) 8-8-2013 filed track one, Trying to speed up approval.
2) Paid $2670.00 to continue examination
3) Paid $2000.00 to track one priority
4) Mehar Manku, PhD. argues the basis of rejection with a signed Affidavid, factualy lays out Opheim "obvious" rejection was incorrect. "I have reviewed the Opheim patent application and nowhere does Pheim disclose compositions containing EPA and DHA in free acid form. Instead, specifically directs that EPA and DHA free acids be REMOVED from it's compostions."

POWERFUL FACT BASED ARGUEMENT

5) Another Affidavid by Paresh Soni, MD PhD
6) Attached study compairing the FFA vs methly esters
7) Updated claims 500 trigs, EPA 70/30 DHA, EPA 80/20 DHA, EPA 90/10 DHA...


I really think Amarin's going to pull this off. AZN would have flat out wasted $260 million if Amarin get's a NOA.

Excellent, it would be great for Amarin to succeed, Amarin would own Epanova IP. It would likely put a hault to AZN's NDA.

Zum
Appendix F in GSK Lovaza response contains Dr. Bays article, hummm that might be a sign.

http://www.regulations.gov/contentStreamer?objectId=0900006481391627&disposition=attachment&contentType=pdf