Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
I do not think that any management could secure ANCHOR. Most of the market were confident and thought that ANCHOR will be approved. It’s still not clear why FDA acted as it was, but I do not want to be “Mel Gibson”.
Do not forget that drugs basically approved based on hard outcome, however the FDA COULD (but not have to) approves drug based on surrogate endpoints, so:
ANCHOR (for zumanto also): FDA did not say it’s useless, they are just not sure it’s effective. They can do it since ANCHOR was not based on hard outcome. (I am not going into the details regarding the process, guidelines and etc., since it was discussed several times, but shortly it was unexpected and they do not have a good reason, top of that: they can do it.)
SPA: FDA could not stop R-IT. If AMRN follow the SPA (and I am sure they will) and R-IT will show the safety profile as expected and eff. will be at least 15% (I expect higher, at least 22%) I do not see any possibility for denial, since R-IT result will be a hard outcome.
negative NCE: not good, but will not effect the company daily operation (low PPS is not good for us as a shareholder, but the relation is exist as a one-way effect only: poor operational result decrease the pps, however the low pps does not effect the company operation)
uphold by OND (SPA): it’s bad and in this case I do not expect a turnover from the next 2 level, so around March 2015 they will go to court
KOWA / time / etc. - Yes, they still have time. Within a month we will know the Q2 result, but let’s work with previous figures:
- Q1 burn was 27M (9M / month) and cash 164M by 03/31. If we apply the same burn rate per quarter they have cash till end of Q3 2015 (18 months), but
- 14% reduction in OPEX is 4,5M so it additional one Q (6 x 4,5= 27,1) = till end of Q41015
- any additional script over the Q1 level is financing 2016
- the operational breakeven is at 30k scripts / week (with Q1 14 OPEX) which is doable (of course not immediately)
- R-IT interim events number will be reached 01-06 2016
- DMC meeting is scheduled quarterly and they could stop R-IT anytime if the data support it.
It does not tell anything for me: we did not see any material (just relevant) news during the last 2 months.
NCE: of course it's not evidence, however - assuming that the judge is independent - I see more chance for grant than denial. However I do not expect any significant PPS reaction for any outcome.
The PPS will be significantly higher if:
- sNDA approved or
- SPA reinstated (DMEP has to approve sNDA) and / or
- Significant - at least 70-75% - increase of scripts or
- R-IT stopped due to eff.
AMRN's management: I don't say they are the best, but most (all) of the critics are emotional.
a.) GIA: if ANCHOR was approved the co. already BO for around $25-30 and everybody call them genius. (I think that most of us thought that ANCHOR approval could not be a problem)
b.) Communication: Be realistic. It’s a small company, but we as a shareholder could expect / claim the same type / level of info as from Apple, Microsoft, etc.
"events":
- Senate / House involvement
- 2 relevant TG studies
- 1 LDL-P study
leak:
Agreement / conclusion - if any - of the meeting will not remain within AMRN & FDA - somebody will trade based on the info
#30476 no_mo_Butterfinger
It's not unusual that companies let the pree earlier with embargo. However, it's unusual in case of material information and amateur by the "journalist" to refer ot.
ladavis23 – lot of question
?
- Agree with JL, the NCE and SPA issue aren’t linked
- NCE decision could be effect the SPA as emotional only
- All “events” since last decision on SPA – late April – is positive, so the chance is better, but maybe not enough
- If my timing estimation is correct Amarin meet / met with Dr. Jenkins this week (agree with leak, next week price action could be interesting)
- NCE: My bet that it will be AMRN’s favor, however it’s not too important now (it was 1-1,5 year ago, now it’s “just” a cash-flow issue – legal cost) . Patents are more important and I believe AZN actions is a good sign: Epanova still not on the market and their statement – no Epanova’s approval, so no case – was funny: they did not argue the patent itself.
- SPA: it’s a big question, since it’s a science. It was unrealistically rescinded, so it’s hard to bet based on facts. I still think that the best scenario for all level of FDA, AMRN and patients – DMEP approve the sNDA – they can do it, they do not need valid SPA for it.
JELIS was known at the time of rescission, so it will not reinstated or sNDA approved based on that. I mentioned the new elements only.
FDA has 3 options:
1.) The 2 TG related studies and the 1 LDL-P related are enough substantial scientific issue to approve the sNDA (by DMEP)
2.) Reinstate the SPA by OND (sNDA HAVE TO approved by DMEP)
3.) Uphold the rescission (by OND)
I think the option 1.) is the best solution for everybody: DMEP, OND, Amarin and mainly for patients.
But who knows ... The first 2 level kept the deadline so Amarin will get the answer from OND on or before August 8.
I hope we will see THE 8-K before the release of 10-Q ...
"Will...
Comparing Vascepa to Makena is totally bogus. K-V just got an FDA approval for an FDA drug which was already widely available and a hell of a lot cheaper.At one point the K-V board thought they were getting 25K a treatment which was ludicrous. The point wa OB-GYN docs were already using progesterone to treat the condition. The docs knew it worked.
Vascepa (purified EPA) was not part of any pharmacopoeia. It is true it was in use in Japan, but Mochita had not applied for FDA approval.
":>) JL"
I could not find the background of FDA' statement regarding HPS2-Thrive: "At the National Lipid Association 2013 conference, the HPS2-THRIVE results were presented along with a subgroup analysis of patients with elevated TG and low HDL-C at baseline; this subgroup did not appear distinct from the overall result (interaction p=0.95)"
As I know HPS2-Thrive subgroup analysis will be released during July (not confirmed, just expected). So what is the basis for this statement?
Slide Set of the results that were presented at the American College of Cardiology meeting on 9 March 2013
I read a lot of calculation regarding breakeven script number. Unfortunatelly these were wrong: the operational breakeven is at app. 25k script / week.
- wholesale price is not interesting. The "real" price after discount, etc is around $126/script (fyi: Q42013CC, Michael James Farrell - Controller: "As has been previously discussed, our revenues have been recorded based on the sell-through method, and our gross to net price adjustments include certain launch year-related factors, which resulted in a lower net price per capsule than the approximately $1.25 net price per capsule that we anticipate achieving over time.")
- Don't forget the COGS! Gross Margin with 65% (after KOWA fee) is $81,8 / script
- The current 32M OPEX should be decreased to 26,8M for 25k script. (with current OPEX the breakeven is 30,3k script / week)
and it's the operational breakeven. All interest, etc payment are top of of it, so additional scripts are necessary to cover.
P&L breakevenn at 25k weekly script with
- 164M revenue
- 65% GM (after KOWA fee)
- 26,8M OPEX (Q1 was 32,3M
Marine: Do not forget that Lovaza's label contains "ANCHOR" trial data till 2014 and was the only drug in class
:) We will see the rest ...
I hope not, since the ruling will be more or less at the same time when R-IT will be stopped. (We have - at least - two add. round within FDA, so we could go to court with SPA around Feb / March 2015 as earliest)
Yesterday / today were "easy" bets. Basically daily / weekly movement does not matter. By end of July it will be 1,9-2,1 (1,95 - 2,05).
Just for fun:
07/02: 1,72-73
07/03: 1,73-74
07/07: 1,78-1,81 (script will be 8,5k+)
Today move is a simple correction of yesterday, as I said #30141 "Tomorrow close at 1,71-1,73".
with AH it's done
#30141 was an answer for you also, I just pushed a reply on other post
Yeah :)
I am still as in #28417 by May 30 2014 "...till end of July we will see the first phase effect of KOWA and the PPS will be around 1,90-2,10 ..."
Tomorrow close at 1,71-1,73
I will be not suprised if we close at 1,78-1,82 today due to end of month and quarter.
The price movement after July 14 (after the assumed meeting between AMRN and Jenkins) could be a sign.
Hi birzinho,
I have a little bit different view:
- they do not know anything
- it's fit to the content otherwise it could be read as "upgrade"
- I do not think that FDA dicusses the appeal with anybody except Amarin (btw: my guess that Amarin received the meeting invitation during this week and the meeting will happen within 2 weeks)
Keep calm and be gentleman. It’s useless to insult each other and rake over the ashes of the past.
Yes, the management could do a lot of things in a different way, however I do not see any big mistake (or we could not measure it yet, ie.: Senior Note conversion).
A lot of people said that GIA was a wrong decision. Yes, it’s right, however ask yourself: if I have a product which is approved and it will be approved for a larger population within a year, should I sell it now or later?
We have to focus on the future and analyze that. So what’s happened since rescission?
- Amarin reached the originally targeted level, the first level which was not involved in the AdCom and the rescission and will check all aspect of the issue (I could not find it, but as I remember Thero said that this is the first level which will take into consideration more than the science)
- a recent pair of studies in the New England Journal of Medicine identify gene mutations that lower both triglycerides and heart disease risk, suggesting that drugs that target that gene pathway could be beneficial
- new paper in Atherosclerosis, coauthored by Emory’s Terry Jacobson, looks at LDL-P, a different way of looking at LDL that has been proposed to be a better measure of cardiovascular disease risk
- U.S. House of Representatives / U.S. Senate Committee on Appropriations dealing with the SPA rescission in the accompanying report and requested several action / answer from FDA
I think these are a good / positive thing and I do not know any negative.
Is it enough?
I do not know. Maybe Jenkins also does not know yet.
We will know it app. within 45 days.
Good question. If they decide the rescission now: it's definitelly no and ANCHOR approved, however since it's already rescinded my guess: 45% reinstate, 55% uphold (it's always harder to overturn something)
Agreed. Now (on or before Aug 8) or R-IT will be approved based on interim result or on DMC decision.
Pros:
- With rare exception, FDA has historically considered granting approval for lipid-altering drugs based on favorable changes in the lipid profile
- TG as a valid marker confirmed by 2 studies
- LDL-P as a valid marker confirmed by 1 study
- it’s safe
- it has not any side effect
- unworldliness of Congressional Record and the 1997 PDUFA Goals Letter
- Senate’s / House’s query
Cons:
- drugs basically approved based on hard outcome
- it was rescinded
Amarin BD for AdCom: "Total LDL-P concentration decreased 7.7 percentage points with Vascepa 4 g/day versus placebo (p=0.0017) and decreased 7.5 percentage points for 2 g/day Vascepa versus placebo (p=0.0013), which was driven by decreases in small LDL-P concentrations (–13.5 percentage points for Vascepa 4g/day (p<0.0001) and –14.7 percentage points for Vascepa 2 g/day (p<0.0001), both compared to placebo). LDL-P size increased with Vascepa 4 g/day (+0.5, p=0.0031) and 2 g/day (+0.5, p=0.0007) compared to placebo."
and now:
"We now have real-world evidence from a large-scale study of commercially insured patients to support the use of LDL-P measurement as an LDL management tool, based on the more favorable clinical outcomes we observed in patients achieving target LDL-P levels, compared to LDL-C targets."
Study Published in Atherosclerosis Provides First Large-Scale, Real-World Evidence of Link Between Low LDL Particle Levels and Reduced Risk of Cardiovascular Disease
sts66 (and chas1232123),
Do not get me wrong: I do not say FDA played an open, cooperative role. Their action against any real, valid logic.
FDA definitely not breached the guidance, however I analyzed again the guidance and have to say ‘salute’ … It's not confusing, it's tricky ...
“If the materials do not contain information that, under certain circumstances, could be considered to be confidential commercial or trade secret information belonging to a sponsor, the portions of the timelines (see Appendices) that pertain to sharing our briefing materials with sponsors will not apply.“
"The two week BD release rule" - such rule does not exist!
The rule: "21 through 14" - "Business Days Before Meeting" "We will send a copy of our briefing materials (or relevant portions thereof), as prepared for public release, to the sponsor to review"
Unless, you have access to AMRN internal system / information you could not know when and what was sent to / communicated with AMRN.
"No later than 2 full business days before the day on which the sponsor’s topic will be discussed" - "We will post on our Web site both the sponsor's and the agency’s publicly available briefing materials." - DONE
Read the Guidance: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM125650.pdf
and EPADI CP did not challenge the BD release date ...
Maybe you are confused since - as I remember - FDA usually release the BD to the public 2 weeks ahead, but according to guidance it's required by 2 full business day.
The FDA failed to provide AMRN the Briefing Documents 2 weeks in advance of the Adcom per their guidelines
I could not say no, but in the previous 2 rounds were not delay.
R-IT:
- with 'updated' enrollment data: 50-50% splitt of the period enrollment between begining and end of the period (assumung linear enrollment during the period) and
- with 'updated' event rate: 5,00% - the design change (TG min. 150 increased to min 200 in May 2013) was due to lower than expected event rate
- eff. 22%: assuming 1:1 relation between TG and eff. ('based' on studies and ANCHOR data)
YTD: 418 events
For 90% power: we need 725 events / May 2015
interim analysis (60%, 967 events): Jan 2016
100%, 1612 events: Nov 2017
Take a break:
Exactly: "They have an opportunity to ask us questions along the way. There's typically an opportunity for a face -- one face-to-face meeting and follow-up questions. And then there'll be a period after those occur that the FDA typically responds in roughly 30 days"
more
Q1 CC: "And then we'll probably end up meeting with him 30 days after we submit. And then after that, he should get back to us within another 30 days."
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM343101.pdf
End of July / early August for final decision of OND, but
'Amarin was informed in late April 2014' (10-Q) - so let say April 30
Amarin has 30 days to fill appeal - May 30 as the latest
FDA has to reply within 30 calendar days from the receipt of the formal request - it' June 29:
a.) complete the review
b.) unable to complete the review and respond within 30 days, the Official should notify the sponsor, explain the reasons for the delay, and discuss the time frame for completing the review
c.) Where additional data or input from others are needed to reach a decision on the appeal, the 30 day response should be a description of the plan for obtaining the information (e.g., requesting further information from the sponsor, deciding to schedule a meeting with the sponsor, bringing the issue for discussion at an advisory committee).
My guess: "deciding to schedule a meeting with the sponsor"
BB,
It's not a question for me, that Vascepa is good for the public and should be approved for ANCHOR (safe and better than "labeled" drugs - niacin, fibrates). I just could not find any written / announced procedure (#29625: "no existing, available guideline for lipid-altering drugs and for “when substantial scientific issue essential”") which was breached by FDA. Of course they breached the unworldliness of Congressional Record and the 1997 PDUFA Goals Letter.
FDA has to contact with Amarin this week (if did not yet).
Does not closely related to ANCHOR, but ...
Now that it has a court ruling in its favor, the FDA could try to extend its authority into other areas, according to attorneys. The next time, it could come equipped with a stronger basis for rescission than political pressure, such as consumer safety, they say.
"You have to consider that the FDA can be very creative when it comes to justifying any decisions the agency chooses to make," Stearns said.
http://www.law360.com/articles/436821/after-win-fda-may-backtrack-on-more-device-approvals
Regarding the Bill:
http://thomas.loc.gov/cgi-bin/bdquery/z?d113:HR04800:@@@S
http://www.whitehouse.gov/sites/default/files/omb/legislative/sap/113/saphr4800r_20140610.pdf
House Committee on Appropriations Chairman Hal Rogers has stated that his goal is to pass all twelve regular appropriations bills for 2015 before Congress has a recess in August.
Regarding the SPA reinstatement and ANCHOR approval:
The SPA and ANCHOR approval is two ‘separate’ issue, however:
a.) if SPA will be reinstated the Division has to approve ANCHOR
b.) the Division could approve ANCHOR without SPA reinstatement
Without assumption for the outcome, the facts:
- Drugs basically approved based on hard outcome, however the FDA COULD (but not have to) approves drug based on surrogate endpoints
- With rare exception, FDA has historically considered granting approval for lipid-altering drugs based on favorable changes in the lipid profile
- no existing guideline for lipid-altering drugs (as I know: Clinical Evaluation of Lipid – Altering Agents / Clinical Medical Draft - 4/16/2010 / Withdrawn - http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079655.pdf)
- During the pre-IND meeting in 2008 FDA discussed and noted that there were ongoing cardiovascular outcomes trials -- ACCORD-Lipid, and AIM-HIGH, to name two -- that these trials would provide important information on the incremental benefit of adding second lipid-altering drug to statin therapy, BUT they did not conclude anything till the AdCom’s BD, meanwhile ACCORD-Lipid was published in 2010 and AIM-HIGH in 2011.
- According to FDA the currently available data from studies of other therapies do not support use of drug-induced reductions in serum triglycerides as a basis for approval of an indication that DMEP views as ostensibly and impliedly an indication to reduce the risk of cardiovascular disease – HOWEVER these studies were different dugs and different target population
- Although treatment effects of non-statin lipid-altering therapy have been suggested in several trials in variably defined high TG/low HDL-C subgroups, the hypothesis has not yet been tested that a patient population can be prospectively identified who will benefit from such therapy
- Two recently published study strongly support the hypothesis, provide encouraging new data connecting reduced TG levels to reduced CV risk but not confirmed it
- DMEP stated that information submitted by Amarin supports testing the hypothesis that Vascepa (icosapent ethyl) 4 grams/day versus placebo reduces major adverse cardiovascular events in statin-treated subjects with residually high triglyceride levels, as is being studied in the Vascepa REDUCE-IT cardiovascular outcomes study
- since October, 2013 FDA approved several generic drugs for niacin and fenobirates …
So:
- Did FDA breach any procedure? – No, SINCE no existing, available guideline for lipid-altering drugs and for “when substantial scientific issue essential”
- Did FDA follow the unworldliness of Congressional Record and the 1997 PDUFA Goals Letter? – No. They breached it in every respect.
- Was the hypothesis changed? - Not really. It’s still not confirmed but the citied studies did not null the hypothesis due to different target population (moreover subgroups and recent studies give more support, make it stronger)
- Was FDA ‘fair’ with Amarin? - No, since they did not notifying Amarin within a reasonable period of time after FDA becomes aware of new science.
- Will FDA generate any damage for patients if approve ANCHOR? - No, MOREOVER reduce the risk since Vascepa is safer than the approved drugs (niacin, fibrates)
- Has to FDA approve ANCHOR? - No
"As for triglycerides themselves, “do they just keep bad company or are they independently doing something to risk?” asked Dr. Robert Hegele, a heart disease expert at Western University in London, Ontario, who was not involved in the new studies. Those studies, published in The New England Journal of Medicine and funded by the National Institutes of Health and the European Union, provide “a very, very strong type of evidence,” Dr. Hegele said, that triglycerides are in fact a cause of heart attacks."
http://www.nytimes.com/2014/06/19/health/scientists-identify-mutations-that-protect-against-heart-attacks.html?_r=1
FDA / Mr. Jenkins,
Here is the requested substantial scientific issue to determining the efficacy of Vascepa, so you could do the right thing.
ps.: Hey Coleman, if you are not completely foolish approve ANCHOR before Jenkins reinstate the SPA.
I agree with the FDA: the science was changed since 2008. … regarding the target population …
Assumption: something taken for granted; a supposition: a correct assumption.
Synonyms: presupposition; hypothesis, conjecture, guess, postulate, theory.
„With rare exception, FDA has historically considered granting approval for lipid-altering drugs based on favorable changes in the lipid profile, with the assumption that these changes would translate into a benefit on clinical outcomes.” –from FDA’s BD
“Recent clinical trials and meta-analyses have failed to confirm definitive cardiovascular benefit with EPA and DHA supplementation, however.” –from FDA’s BD
“Although treatment effects of non-statin lipid-altering therapy have been suggested in several trials in variably defined high TG/low HDL-C subgroups, the hypothesis has not yet been tested that a patient population can be prospectively identified who will benefit from such therapy.” –from FDA’s BD
Just for 'fun':
Jenkins pointed out the logistical difficulty of going back and re-visiting previous approvals. “A system that required the agency to revisit every prior decision as science evolves and standards change would make the regulatory process impossibly cumbersome and burdensome on both the agency and sponsors of approved indications.”
I would like to add: "A system that required the agency to remember every prior decision would make the regulatory process impossibly cumbersome and burdensome on the agency"
Since, after the referred studies and after Vascepa's SPA rescission they are STILL approving ANDAs with active ingredient: niacin or fenofibrate.
So once again, the three study results were 'enough' to rescinned Vascepa's SPA, but not enough to withdraw previous approval AND NOT ENOUGH to deny ANDAs ...
BB,
Hope you have right, but for me the Act is equal with the Bill. (The report is 'To accompany S. 2389'). They voted about the Act and the report together.
(On May 29th, the U.S. House of Representatives Committee on Appropriations voted 31-18 during a mark-up session to send to the House floor its version of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2015, along with an accompanying report.)
Your example:
Seafood Advisory. — 'as directed in House Report 112–101 and Senate Report 112–73 by June 30, 2014.' (The original reports were for the fiscal year 2012)
ANDA Review Prioritization - the issued doc is the 'Guidance for Industry / ANDA Submissions / Content and Format of Abbreviated New Drug Applications' - so it's not the report to the Committees
BB,
'enactment of this Act' is the date when the Bill passed and signed and not the date of Committee's report, however I think it's not the most important part of the report since it 'just' about report to Committees
I think the important parts are:
'fundamental questions concerning FDA’s adherence to the statutory and regulatory guidelines that apply to the SPA process as well as to questions concerning fairness to the sponsors. The Committee would like to reiterate that FDA is expected to adhere to the established standard as informed by the Congressional Record and the 1997 PDUFA Goals Letter' and
'The Committee also expects that, as a matter of public policy and fundamental fairness to the sponsor, FDA should be accountable for continued diligence in identifying issues that bear on the continued enforceability of a SPA agreement and in notifying the sponsor of such issues within a reasonable period of time after FDA becomes aware.'
Basically the Committees said:
- FDA did not follow guidlines and policy
- did not notify the sponsor in time
The case similar, but not the same:
- as I know (could not find, it was withdrawn in 2010) no existing guideline for lipid-altering drug trial for primary end-point
- FDA 'realize' the new sciense in BD only
- new sciense is based on different population ("Subgroup analyses from JELIS, ACCORD-Lipid, and AIM-HIGH suggested that patients with elevated TG and low HDL-C might experience a greater potential treatment benefit with additional lipid modifiers to a statin regimen; however, the available HPS2-THRIVE subgroup analyses do not seem to support this hypothesis. Unfortunately, none of these trials were specifically designed to recruit and investigate patients with moderate hypertriglyceridemia with or without low HDL-C; therefore, these results are hypothesis-generating and require validation.)
- new sciense based on different type of drug studies (Triplix EMDAC: "no additional relevant clinical evidence provided by ACCORD-Lipid")
- FDA did not follow any protocol (ie.: determination of new sciense is not equal with rescission of SPA)
- Senate / House involvement
- several CPs