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It’s fine with me. They have to communicate if they could tell any real info:
1/a. We dropped the appeal and got the CRL with the recommendation of re-submission / new accelerated submission.
1/b. We dropped the appeal and got the CRL without any recommendation.
2/a. We submitted the appeal to the next level and working with FDA on the compromise. (Possibility: 0%)
2/b. We submitted the appeal to the next level and FDA did not address the ANCHOR sNDA in their communication.
LMAO Brilliant
"There has been no determination on the ANCHOR sNDA. We tried to engage FDA on the ANCHOR sNDA with every available opportunity over the last 10 months and offered a number of compromises. But FDA maintained the SPA appeal and sNDA are two separate matters and did not address the ANCHOR sNDA in our communication on the ANCHOR SPA appeal." CC on Sep 16
ps.: brinzinho - check your inbox @yahoo.it
R-
Amarin could sue the FDA after the final denial by the Commissioner. 2(3?) level is remaining till that and one level is at least 2 months, but could be 5. The final denial could be expected around March 15 and the case could be filed in April as the earliest.
Amarin has two basis:
a.) FDA’s approach is wrong. It’s a science dispute.
b.) the timing of the rescission. It’s the stronger, since FDA has 2 years after Accord-Lipid AdCom, however if the period counted from the date of the submission … (sorry, it’s a new think. I do not like it also)
The final ruling date (mid-2017) is just a guess from me, however do not forget that it could be more than one round / court if the first ruling will be appealed. ie.: Ivy vs FDA first round was 2 years!
Ivy vs. FDA
D.C. DISTRICT COURT RULES FDA HAS INHERENT AUTHORITY TO RESCIND 510(K) CLEARANCE IN "RARE SITUATION
brinzinho – if necessary feel free to translate it
Kiwi,
You were clear, but it isn't enough, you have to be (also) precise / careful ...
So could Amarin ask FDA for another earlier interim analysis ...say Oct 2015?
Amen.
Unfortunately we won't see the order within 6 months (if they continue to appeal it will be still at FDA) and FDA did not breach the SPA, it was terminated entirely by them.
Theoretically it is possible, as part of the SPA it could be modified by mutual agreement, however I did not find any, (public) precedence.
Hi Kiwi,
I always forget that I have to be very, very, very precise (not because of you)
"to my knowledge no CV Outcome Trial has been stopped before the first, predefined interim analysis - Correct
The stop is recommended by DMC (applying the predefined stopping rule) and the data won't be unblinded to the sponsor immediately. More: Establishment and Operation of Clinical Trial Data Monitoring Committees
First of all I read the full post, but commented these parts only.
I have a sense that if I tell you it is not an open door, it's a french door: you will not stop ...
Now is a little bit too early. They have to:
09/14-05/15
- stop the appeal by Sept 12 ...
- try to reach a compromise with FDA
- increase script#
- try to license / sell rights on ex-Amarin market (current and future)
06/15
- based on actual cash position and outlook (actual script#) and overall data of R-IT (expected time of interim) raise fund if necessary
.
.
.
.
.
and the first target could be the biggest bagholder: Pharmakon.
BO is not a possibility, since the possible future value of the company is the same as it was 1 year ago but I do not think that anybody will offer it on a short-term. (BO is based on current and future value, not on pps) and it is not good since it saves the drug and not he company.
Ajax,
Two comments:
1.) R-IT powered at 90% for 15%, with higher eff. the power will be higher
2.) FDA does not have any right regarding the trial (exc. safety). The method is:
- DSMB recommend the stop if the result meet with the stopping rules
- Steering Committee agree or disagree
- the final verdict will come from Amarin and they have to be sure that the result is strong enough, power is - let say - 95%+
Hi Kiwi,
To be more precise: They have more or less enough cash till interim, however they have to raise fund earlier (if necessary), could not run it till the last $. The next four Q (inc. the current) will be crucial to see what is the GM. It is depends on scripts and GM% (Maybe I will set-up a matrix - GM%/script - just for fun but it takes more than 5 minutes).
JL could be right (his argument look like valid) regarding the timing (as I remember Q2-Q3 2015) of the meaningful eff. data, however I could not find any study which was stopped before the first interim analysis...
Amarin could do one thing (top of the usual business: increase scripts): request a modification of R-IT's SPA, determine a 2nd, earlier/lower interim analysis event number. They have to be very careful with it.
Acc. to my best calc., as of today: 5,2% placebo, 7 377 enrollment, 25% eff., - 510 / 15% - 539 events
Best,
HD
L-
I (hopefully) understand what is going on just could not see the future, does not have the Magic Ball as you. However the Magic Ball is useless if you could not use it …
“it's not about looking for a different management expecting different results. It's about knowing the difference between a minor league and major league team...” – it is a very good summary of your “thought” …
Management change is always explained as “we expect better result”. Nobody change the management just for fun. It’s true that the change has a positive effect, but without better performance on a short-term only.
The best thing that the management could do is to be silent regarding their plan, action with FDA at the current stage.
a.) if they do not know anything new, what could they say. And folks like you will call it “BS” immediately
b.) if they have any new info, development with the FDA we have to be “the last” who will know it. (I hope Amarin’s employees do not know anything also.). It is against any standard to talk publicly about ongoing discussion. As it is ongoing …
We know that we have to know about it now: “As to steps forward, aside from stating that we're again reaching out to FDA for resolution on the sNDA, we will not detail our plans on this call. We have continued to consult with our nationally recognized regulatory clinical and legal advisors who share our passion for approval of the ANCHOR indication”
Yes, I think the "operations" will remain in tack (at least on short- and mid-term) if the stock drops to .75 cents / .50 cents. Equity is not collapsing, the Market Cap is collapsing. These are two different thing. Pps is force the company to do something to avoid delisting issue (if any), however it will not affect the daily operation. It could affect the ability of the company to get new financial if necessary. (In my view it could be a topic around Q2-3 2015 since the cash is enough till Q1 2016 with the current revenue level.). Do you really know what will be the CF in the next 7-9 quarter? I do not.
Good luck, if you are investing based on the pps only and does not look the fundamentals and outlook.
You looks like the FDA: supporting your assumption with your assumption, conclude something based on non-validated endpoints, ignore the standards and would like to set-up rules instead playing according to that.
Agree. I forget to use "maybe" and cover all aspect ...
Yes, I am here and watching. What is the "news"?
Was new study released about EPA with negative safety or validated inefficiency? -no
Did the company spend all of the money during the last week? - no
Did they loose NCE or patent case? -no
Are we closer to BK or dilution? - no
"Only" the pps is lower. It's not good, the possibility of delisting is higher, however we are still far away from the end of the story. (They have cash till end of Q1 2016 without increased script#.)
Thx, good summary (one correction: JL does not agree with the "no breach" / "no change of terms of SPA" conclusion.)
"the separation FDA put between the SPA and the sNDA isuue, is something a judge can consider no more than waste paper" - agree, but the question is: when?
I think that any ruling by the judge could be expected around mid-2017, get the answer regarding the sNDA (no more appeal) now, makes more sense for me.
Maybe I was not crystal clear (again ) . The "fairness" (timing) isn't the only issue, it is the issue that could not be justified by the FDA, the judge will not accept any excuse for the the 2 years (I am not remember exactly for the exact case: 10 months was acceptable by the judge.)
If you read the R-IT CC transcript carefully, the situation is worse:
"We are certain that the FDA has considered not only the positive ANCHOR study results in this analysis. But also more recent data such genetic studies, which as Steve will discuss, add to our confidence and the positioning of REDUCE-IT to be successful."
re 35121: see 35109
It's the real question!
They could reevaluate their approach immediately after the Trilipx/ACCOR-Lipid AdCom in 2011 (or after HPS2-Thrive result in 2012) based on the same data... They had at least 2 years to do it before the AdCom / rescission.
JL,
Yes, it’s not my native language and I know that my grammar is not perfect. However, it’s not a problem to understand everything and I saw a lot of contracts under US law.
(Hungarian: Like Finnish and Estonian, it belongs to the Uralic language family, and is one of the few languages of Europe that are not part of the Indo-European family. It is an agglutinative language.)
As I see / understand we have a different opinion about
Was it a breach or not?
What is necessary for the determination?
“A clinical protocol assessment will no longer be considered binding if the director of the review division determines that a substantial scientific issue essential to determining the safety or efficacy of the drug has been identified after the testing has begun”
It’s part of the SPA(‘s term). It is very specific when, by whom and what is necessary to rescind (terminate) the SPA. FDA rescinded the SPA based on this and I hope we could agree (I could not read this term differently) that the FDA has the right (ability) to rescind the SPA. Based on this FDA did not breach the SPA (exercise the right could not be a breach) and did not change any term of the SPA, they nulled the SPA itself. SPA is not about the sNDA, it is about the study and intend to form the primary basis of the efficiency claim / sNDA. (” change the terms of the SPA” – what was changed exactly according to you?)
However to come to final conclusion we have to answer the second part also, what is necessary for FDA to use this term of SPA, exercise their right.
The SPA doesn’t give any guidance, exact definition (“substantial scientific issue essential” isn’t the condition for determination it’s part of the determination itself) this is – agree with you – “what a reasonable man would do” type of contract, the director of the review division cannot merely claim to have found a substantial scientific issue.
However, the FDA could reevaluate the situation and adopt a new approach based on unchanged, existing data anytime, no new data is required for it, however “new” data were available in this case (Not exactly the same, however similar:“Fair is Fair; But Science is Science”). FDA has the causes (without value the relevance, a validity by me):
- cited studies do not support TG validity for CVE
- ACCORD-Lipid’s AdCom recommended “transitioning away from surrogate endpoints to relevant clinical cardiovascular outcomes especially for indications for add-on therapy to statins.”
- ANCHOR’s AdCom voted against “lipid/lipoprotein parameters are sufficient to grant approval … prior to the completion of REDUCE-IT?”
- effect that is considered reasonably likely to predict clinical benefit can support accelerated approval – effect isn’t important in this case “But again, that was not something that was discussed with this application” (FDA / AdCom)
- MPC discussed the issue and does not support the reinstatement of the SPA
Based on pure legal approach: FDA did not breach of SPA, did not change the terms of SPA. Amarin could not sue FDA based on these.
Amarin could sue, after go through the appeal process without positive decision, based on:
- a.) FDA basis for the determination is weak, not valid
- b.) FDA did not act within a reasonable time
I do not want (and could not) answer the a.) since it is science, however it does not look as a slam dunk.
Amarin definitely will win based on the second argument: timing. However, the ruling could be something like this: “FDA did not act within a reasonable time, however their determination has merit” (Again, since it is science related I could not judge it.)
All that I would like to say, do not be surprised, disappointed if Amarin will stop the appeal process since it does not have too much, possible benefit (especially on short-term).
"it is safe to say that my homework has been a little better than your homework, at least up until now" - agree, now. However we are far away from the end of the story.
Never mind where we are in September or November, the real season will be started in December. Who cares the first x game if we will win the SB.
"meeting with the FDA regarding NCE in June 2012, BEFORE VASCEPA was even approved. Now, we will never know the details of that meeting specifically" - maybe they were aware of the new approach of FDA regarding the determination of the active moiety (?)
"Getting a no NCE late summer" - are you saying that FDA waiting 18 months due to the meeting and nothing else ... if meeting weren't requested NCE was denied in 2012? Based on ... ? We will never know.
You are supporting one of your assumption with one other of your assumption ... so I "leave it"
JZ and the AdCom?
Agree with you and I never said it was ETHICAL or MORAL. I said it was legal. Not less, not more.
Meanwhile I am not agree with it I could summarize FDA's current view as: V is safe and promising, however we are not sure it is effective or not, and we do not want to approve it without evidence for the current indication as we could approve safe and effective drugs only.
Kiwi,
AZN (and all other BP) could wait, however as R-IT more likely will be successful, till end of 2015 / mid-2016 only if they want to own THE DRUG.
The pps dop $0.2 during the last 7 trading days, due to … nothing. No new info, news regarding Amarin. Maybe it will drop more, maybe it will be delisted (I do not think, but I do not know), however Amarin has cash for the next 2 years, script is increasing (true: could be faster). Pps does not affect the daily operation.
HD
You have right, it is unbelievable. By the way Apple is the same: I purchased some $APPL in May and requested a iPhone6 for testing and the exact release date. However they never contacted with me meanwhile I was a shareholder... We have to fight to replace Apple management also.
JL,
Hi Kiwi,
"adding enough DHA to Epanova" isn't an option under the current approval.
Agree, it does not stop the trials.
If I was AZN I do the same, as I do not have other option and I did not pay too much for Epanova ...
AZN has $$$ - agree, check
and reps to push - agree, check
Why had not been launched in the last 4,5 months? Hmmm ....
Oh, yes Amarin has the patent. The patent is strong enough - at least - to stop the launch of Epanova till it is under dispute.
JL,
JL,
The FDA will not act anything regarding the sNDA, since they could not, till the appeal is ongoing. The action is different w and w/o SPA.
It is indifferent that SPA is a contract, agreement or assessment (btw: the value / $100M does not determine it). The rescission was totally legal as the director was entitled by the statue to do it.
I agree with you that the timing is unacceptable and their reason is weak, however I could not say and you could not guarantee that the judge will rules in favor of Amarin.
The business could not be run based on emotion, based on “right is on our side” on a long-term. The possible scenario:
a.) continue the appeal process, sue FDA, and win the case in 2017 after R-IT stopped based on interim: no gain
b.) continue the appeal process, sue FDA, and win the case in 2017 before the final result of R-IT stopped: gain app. 6-9 months
c.) continue the appeal process, sue FDA, and lost the case in 2017: no gain
d.) stop the appeal process, get a CRL without recommended actions: no gain and lost the opportunity to sue the FDA
e.) stop the appeal process, get a CRL with recommended, reasonable actions (ie.: resubmission in different form): gain something now (ANCHOR data on label w or w/o modified indication)
Amarin has to estimates the possibilities (short and long term, advantage and disadvantage). In case of “appeal and sue” no short-term gain and the long-term loss is small (poss. b.)). If they stop the appeal they could (not guaranteed) gain something on the short-term and they won’t lose too much (max. 6-9 months) on long-term.
FDA was (and will be) within the legally allotted times for their answer during the appeal process. However, if not the Performance goal is: 90% of such answers are provided within 30 calendar days of the Center’s receipt of the written appeal. To sue FDA as "bad faith on the FDA's part" is ...
As you cited "This is perceived to reduce risk by eliminating the fear that a positive outcome in Phase III might not result in approval if the trial design is not acceptable to FDA.".
FDA did not breach the SPA with rescission, since the director of the review division entitled by the statue "to determine that a substantial scientific issue essential to determining the efficacy of the drug has been identified after the testing has begun".
Amarin could sue the FDA for:
a.) timing of the determination - they can win this argument as the action was not within a reasonable period of time after FDA becomes aware of the cited studies, the basis of their new approach for biomarker based approvals
b.) the determination by the director of the review division is wrong - as it's science (and TG isn't a validated surrogate endpoint) it's not black or white (more details: #34685)
It could be less time (by app. 6-9 months) IF R-IT will goes till the end, if interim result won't be good enough to stop the study. Based on JL's great assumption it is more likely that the study will be stopped after interim analysis in 2016.
I hope also or if it is not possible reach an agreement before CRL and release the "solution" together with CRL.
FDA issues the CRL if they cannot approve the application in its present form [no question about it]. CRL provides a more consistent approach to informing applicants of changes that must be made before an application can be approved, with no implication regarding the ultimate approvability of the application.
Based on the agreement (if any) Amarin could resubmit the sNDA as Class1 (2 months deadline) or Class2 (6 months deadline).
a.) they have to go through the FDA appeal process before file the case. At least 2 levels (maybe 3) are remaining and that is at least 4/6 months, however could be longer 6/9 months - earliest time to file is Q2 2015
b.) it's not a slam dunk - max 50/50% as the best
c.) final ruling takes 2 years - mid-2017
d.) ANCHOR sNDA is pending until appeal is ongoing, DMEP could not issue the CRL, since they have to act differently w or w/o SPA
Which is better:
1.) wait additional 2,5 years for a possible, but not sure court ruling (and don't forget that R-IT maybe will be stopped due to eff. or the end of the study will be near at that time)
2.) stop to appeal, get the CRL and try to include the ANCHOR data on label w or w/o new, modified 200-500 indication
Three, as
Center for Drug Evaluation and Research - Janet Woodcock, M.D., Director
Office of Medical Products and Tobacco - Vacant
Office of the Commissioner - Margaret A. Hamburg, Commissioner
Each level takes between 2-5 months. Previous levels were:
DMEP: 2 months
ODE II: 3 months
OND: 4,5 months
ps.: I am not 100% sure in Office of Medical Products and Tobacco, so at least 2 levels remaining
Formal Dispute Resolution:
Appeals Above the Division Level
VI. REPEAT APPEALS
If a sponsor’s appeal is denied at one management level, the sponsor can appeal the same issue to the next higher management level in the chain of command in the center. After exhausting the center’s management levels, a sponsor can request review of the center’s decision by the FDA Commissioner of Food and Drugs. As stated in § 10.75, requests for such review should be submitted to the FDA’s Ombudsman.15 Each appeal to each management level should follow the process provided in this guidance. If a sponsor is appealing to the FDA Commissioner, copies of the appeal should also be sent to the centers as described in section IV.A., How to Request Formal Dispute Resolution.
"So in your opinion the Anchor trial data on label is unlikely until Reduce-It?"
No, 2.) and 3.) could contains ANCHOR data and I could imagine that they could submit a new sNDA about it in case of 1.).
I do not think FDA hates Amarin:
NCE: They always applied the active moiety approach. The new element was, how they determined the active moiety. I am still believe - based on earlier cases sponsor vs FDA and sponsor vs USPTO - the court will overturn it as the statue is about active ingredient.
No ANCHOR as it is currently, but data on the label and modified indication is still possible. However, to go further with "ANCHOR" the appeal process should be finished.
My view:
They will hold decision on Anchor sNDA until the SPA appeal is ongoing, since if SPA reinstated (it won't) the revision division has to use SPA as the primary basis. Without reinstatement of the SPA, they could evaluate the claim without "restriction" and send their decision.
Amarin has 30 days (deadline: Oct 12) to submit the appeal to the next level. I hope they won't and will send a letter about it to FDA well before the deadline.
After the end of the appeal DMEP could issue the CRL since it's clear they will not approve the application in its present form. They will recommend actions that Amarin has to take to place the application in condition for approval.
1.) finish R-IT and submit a new sNDA based on R-IT's result
2.) resubmit as Accelerated Approval (?)
3.) resubmit as Class1/2 with modified indication / Draft labeling
I guess Amarin requests opportunity for hearing continuously and it will be granted, before - hopefully - or after the CRL.
To exhaust appeals to file suit on SPA (around Q2 2015) is useless since any final ruling could be around mid-2017 as earliest.
Check your inbox.
For all: 16-Sep-2014, Amarin Corp. Plc (AMRN), Business Update Call
I do not know any public source. I got it by email.
You could find (the relevant part of it) within #34692. It was a reply to you
L-
First of all, meanwhile we give a “special” attention to Amarin, it’s just one of the thousands for WS and one of the hundreds for FDA. The pps does not reflects anything else than the market’s sentiment about the outlook. I do not think that any company will revise the financial forecast (inc. pss) for a long-term if a new management will be in place, since the condition (NCE, SPA, sNDA, etc.) will remains the same. The pps was higher and could be higher with the existing management.
Unfortunately, I do not have a crystal ball as you. I could conclude anything based on facts only. All of your sentiments are based on the current pps and if the pps will be higher your view will be false. (btw: We still do not know exactly what is Amarin current plan. As IR was „seemed confused to be honest” (by mrmainstreet) and during the CC they said ”As to steps forward, aside from stating that we're again reaching out to FDA for resolution on the sNDA, we will not detail our plans on this call.”)
According to you the pps could be significantly higher with different management as new management could be successful with all issues. The issues:
GIA:
We could not make a conclusion about it as the company is still exist and – without increased revenue – they have a funds for the next 8 quarters, till mid-2016. To conclude anything now is premature.
NCE:
The NCE is depends on the drug (Vascepa) itself, so new management has to deal with the same drug. The reason for denial was the “active moiety” (based on FDA’s regulation), however the statue contains “active ingredient”. FDA applied the moiety approach since the beginning – it is not new – they applied “new” (never applied before) approach to determine the active moiety. Based on cases in the past it will be reversed by the court.
SPA:
According to Amarin “In our communications with FDA, it is clear that in the backdrop of these HDL studies, FDA has revaluated the situation and has adopted a more conservative approach than previous applied for biomarker based approvals targeted towards cardiovascular risk reduction. … FDA noted to us that this illustrates that the science related to the use of drug induced changes in lipid parameters as surrogates for cardiovascular risk reduction remains unstable and fluid.” We do not know that any other reason was behind the issue or not, we saw some assumptions.
Meanwhile Amarin is not big enough to reach anything at FDA, are they big enough to be penalized by FDA? As:
JZ’s sales of shares:
When does the FDA monitor insider sales? (Agree w sts66, never). All of these was under Rule 10b5-1 trading plan. Before (3/23 – 160,000 , 5/29 – 150,000 and after (7/27 – 150,000, 10/1 – 150,000) the approval.
The “source” of the sales was “On December 21, 2009, the reporting person was granted an option to purchase 1,170,000 ordinary shares under the Amarin Corporation plc 2002 Stock Option Plan. The stock option initally vested in four equal annual installments beginning on January 1, 2010. In December 2010, the Issuer's Board of Directors approved the acceleration of the vesting of this award by six months such that the option vests in four equal installments and will be fully vested on July 1, 2012” and he has a lot of shares from other grant and purchase.
FDA wouldn't allow JZ to attend ADCOM:
We do not know he was there or not. (Note: the following is based on 2013 Meeting Materials of Endocrinologic and Metabolic Drugs Advisory Committee - 6 events inc. Amarin)
The final roster never includes participants from sponsor, sponsor’s presentation was by Regulatory Affairs, Medical Leader, Metabolism Development, etc, never by the CEO and the presenters were determined by the sponsor, not by the FDA.
Amarin refused FDA’s offer in January:
I could not harmonize FDA’s public communication (“Although the indication strictly speaks to reduction in lipoprotein levels and improvement in numbers, this indication for this population certainly implies that one should expect cardiovascular benefit from treatment.” – during AdCom and “changes in lipid parameters as surrogates for cardiovascular risk reduction remains unstable and fluid” - transcript of the CC) with any acceptable offer. What we “know” about the offer?:
- SPA back on the table: Assuming we are talking about ANCHOR’s SPA - Could you give me any example how the SPA could be changed to affect anything? Study was finished, data was analyzed. The one and only reason of the rescission was that FDA does not want to approve ANCHOR, they do not want to use the SPA as a primary basis.
- “Limitation of Use” in Black Box: Limitation of Use was, is and will be part of the label till successful R-IT. It is not BBW currently, but I do not think that the company refused to show it as BBW if it was the condition of the approval.
Top of these the company’s statement is clear: “We tried to engage FDA on the ANCHOR sNDA with every available opportunity over the last 10 months and offered a number of compromises. But FDA maintained the SPA appeal and sNDA are two separate matters and did not address the ANCHOR sNDA in our communication on the ANCHOR SPA appeal.”
Based on these I do not see anything behind your opinion, however I could be wrong. Could you please tell me:
- How could be the NCE granted with different management?
- Could you give any, theoretical example of FDA’s offer (refused by the company)?