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Data collection is not "intersting". Result / conclusion is important.
I could not find reference for prelim data during thje CC only that "enrollment would be completed somewhere in the first half of 2015."
It was a good article reg. interim data: http://seekingalpha.com/article/1901351-amarin-todays-market-is-underestimating-the-probable-success-of-reduce-it
and as we all belive that Vascepa is so effective, I could not imagine a 2015 interim rsult / conclusion
Unfortunatelly the preliminary data will be released in 2016 and not in 2015
"market Vascepa for Mixed Dyslipidemia, with the tacit agreement to acknowledge, that there was no data as yet to prove that lowering Trgs improved Patient Outcomes"
For me it is not label compromise, it is exactly what they would like to get ...
"That was all FDA wanted, saving face and revising the SPA. It would have allowed AMRN to basically still market Vascepa for Mixed Dyslipidemia, with the tacit agreement to acknowledge, that there was no data as yet to prove that lowering Trgs improved Patient Outcomes, and make the SPA contingent on Reduce-IT RESULTS."
I am confused, please help me to understand.
FDA want to allow ANCHOR (for me the description is equal w ANCHOR), but Amarin refused it and would like to get REDUCE-IT under ANCHOR SPA?
I could not remember that Amarin would like to get a wording on label "lowering Trgs improved Patient Outcomes" (or not to show on label that there was no data as yet to prove that lowering Trgs improved Patient Outcomes)
As I see the situation is "opposite": FDA stated that there was data to prove that lowering Trgs NOT improved Patient Outcomes"
(btw: the first sentence is so interesting based on the FDA's new "science":
"In its communication to Amarin, 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. However, DMEP reiterated its position expressed at the October 2013 Vascepa advisory committee meeting that 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."
FDA approach is true, but for normal or border-high TG and not for high TG.
I do not believe in the corruption theory (maybe on some level yes, in this case, but I do not see the reason for that), maybe it's a simple ego issue currently (but not for the reason you mentioned).
My science is:
1.) TG higher than 200 (150) should be treated (basically recommended by all org)
2.) no data as yet to prove that lowering Trgs improved Patient Outcomes, since study was not completed to confirm the hypothesis
3.) no data as yet to prove that lowering Trgs NOT improved Patient Outcomes, and sub-groups analysis of studies suggest the opposite (btw: when will be available the HPS2-THRIVE' subgroup data / analysis - I remember for 12 March but I could not find it)
4.) Vascepa reduces TG and safe
So, I do not say that there is 100% correlation between TG and Outcomes (since R-IT is still ongoing), however the current science, sub-groups of studies and all other info are supporting this approach.
Based on Dr. Hiatt's word at ADCOM: Lack of evidence is not null the theory and definitely not confirm the opposite.
I did not expect that DMEP reinstate the SPA, however there is a chance that higher level will (not the current ODE II).
What is it means exactly? I could not fit questions into the process. Only FDA could request more info.
44 + 16 days. 16 days between the acceptance of the meeting and the date of the meeting.
HDG
I hope your assumption is right (post 21684), we could see the interim result before January 2016 and they do not have to wait till the "original" 60% (967 events).
ref: http://seekingalpha.com/article/1901351-amarin-todays-market-is-underestimating-the-probable-success-of-reduce-it
HDG
Based on FDA guidance ( http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM343101.pdf ) and if AMARIN submited the appeal to ODE-II before end of January (I guess yes) it will not a "simple" denial and FDA sent a response to AMARIN (grant a Type A meeting or interim response or explain the reasons for the delay).
Type A meeting: decision on the appeal within 60 calendar days from receipt of the appeal.
interim response: decision on the appeal within 60 + 15-21 (?) calendar days from receipt of the appeal. 15-21 days are necessary for
- additional clarifying information from the sponsor or
- meeting with the sponsor or
- limited discussion with one or more members of an advisory committee or internal or external experts or
- advisory committee review
delay: who knows, but they have to discuss it with AMARIN
Based on the exact submission date and the content of interim response the FDA should render a decision on the appeal between March 22/31 and April 14/22.
Any thought?
IF (?!) FDA does not want to see any CVE word on the label (other than in MARINE) they DID NOT HAVE any other option than rescind the SPA (since based on the result they have to approve it as it is).
Now they could negotiate the label w Amarin.
What do you think?
I do not know we will get ANCHOR or not, we will be BO or not, however I am 100% sure that we have to partnering w sbody (w or w/o ANCHOR) to monetize the potential.
I think we have to wait. As I see:
AdCom was totaly useless (w this question) and not relevant, since
- AdCom vote is not bidding for FDA
- they voted about the sciense and not about Vascepa (to be honest this question - w BD - will be answered as no regarding any TG reducing drug)
My scenario:
1.) FDA will approve ANCHOR indication (maybe w some label restriction) on PDUFA date
2.) Prior PDUFA date "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 (section 505(b)(4)(C) of the Act). If the director of the review division makes such a determination, (1) the determination should be documented in writing for the administrative record and should be provided to the sponsor, and (2) the sponsor should be given an opportunity for a meeting at which the review division director will discuss the scientific issue involved (section 505(b)(4)(D) of the Act). This meeting will be a Type A meeting under the PDUFA goals for meeting management."
2.a.) FDA will approve ANCHOR indication (maybe w some label restriction) on PDUFA date
2.b.) FDA wil not approve ANCHOR
3.) Delay the PDUFA and "the director of the ..."
3.a.) FDA will approve ANCHOR indication (maybe w some label restriction) on PDUFA date
3.b.) FDA wil not approve ANCHOR
1.) 30%
2.a.)40%
2.b.) 5%
3.a.) 20%
3.b.) 5%
As I remmember that will be the time for iterim data (app. 50%)
They will enroll the 2.000 till app end of Q214, however the expected no. of CVE will occur till end of 15
"FACTS SPA is broken" - not yet. SPA is between AMRN and FDA (not with AdCom)
"The FDA convened a panel and asked a question to get enough cover and enough controversy to be able to get away with it even if Amarin has better argument"
AdCom vote is not equal w "director of the review division determines that a substantial scientific issue"
No reason to take any legal action (by AMRN) currently since FDA did not make any decision (they have 'only' recommendation from AC).
5% - approve as it is requested since they have some doubr reg. the science
10% - to fully deny since they do not have any evidence reg. the sciense changed
85% - they will approve w modified label
JL?
Just rewording the BD ...
1. Please discuss the efficacy results from the ANCHOR trial, including the clinical significance of the observed changes in lipid/lipoprotein parameters and your level of confidence that these changes will translate into a meaningful reduction in TG among the target population with CV risk.
2. Taking into account the described efficacy and safety data for Vascepa, do you believe that its effects on the described lipid/lipoprotein parameters are NOT sufficient to grant approval for co-administration with statin therapy for the treatment of
patients with mixed dyslipidemia and CHD or CHD risk equivalent prior to the completion of REDUCE-IT? Please provide the rationale underlying your recommendation.
My understanding of the studies / BD:
1.) Equal or less than 2g is not efficient (as V 2g) - agree, but it is 4g. (statins are also optimized)
2.) If TG is below 200/150 no cardiovascular treatment benefit - agree, but it is TG above 200. (with optimal parameters nobody needs statin.)
3.) 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. - agree, BUT this is the CURRENT assumption / sciense.
So I do not see it as substantial scientific issue essential to determining the safety or efficacy. It just say these results are hypothesis and require validation.
I agree, but top of this the managment has to clarify the exact situation (pls not comment the management).
We have to know more about the exact situation ie.: did they received anything? Will they contact w FDA reg AdCom / science change?, etc.
(Maybe) we will receive some answer during the Q3 CC.
The current picture is not so bright (AdCom vote and FDA BD), however we still have a binding SPA and Vascepa is safe and effective reg TG lowering.
ps.: the current atitude of FDA is definitely inceasing CVE events, so they have to approve ANCHOR :)
Correct me if I am wrong / misssed something but the FDA officialy did not reneg / avoid the SPA as of today. (In my wiev AC's BD is not official way)
If the director of the review division makes such a determination, (1) the determination should be documented in writing for the administrative record and should be provided to the sponsor, and (2) the sponsor should be given an opportunity for a meeting at which the review division director will discuss the scientific issue involved (section 505(b)(4)(D) of the Act). This meeting will be a Type A meeting under the PDUFA goals for meeting management.
As we know none of them happened, so it is still bunding. (?)
"review division determines that a substantial [url][/url][tag]insert-text-here[/tag]scientific issue essential to determining the safety or efficacy of the drug has been identified after the testing has begun"
If u mean that the review division DID NOT makes such a determination it is true as they did not documented it and did not provided to the sponsor. However the BD contains some determination. Maybe it will happen soon ...
From BD: "It was stated that before an indication would be entertained for Ethyl-EPA as
add-on to statin therapy in patients with elevated TG levels, the applicant at a minimum
would have to provide results from a 12-week study with lipid endpoints as well as
initiate an appropriately designed cardiovascular outcomes study. This outcomes study,
known as REDUCE-IT, is ongoing and is investigating whether the addition of AMR101
4 g daily ameliorates residual cardiovascular risk among patients at high CV risk who
have moderate hypertriglyceridemia at LDL-C goal on statin therapy. The study designs
for both ANCHOR and REDUCE-IT were agreed to by the Division under special
protocol assessments."
Not in the last minute, but definitely changed - from BD "prior to the completion of REDUCE-IT".
As we know the completion of R-IT was not required earlier for ANCHOR. The voting question itself was a change.
Lowering TG (above 200) is important? - yes (ie.: http://www.mayoclinic.com/health/triglycerides/CL00015)
Lower TG resulted in less CVE? - questionable, but definetely not no
Vascepa (ANCHOR)
- safety? - yes
- lowering TG (above 200)? - yes
- lowering CVE? - questionable, BUT the question should be answered during Reduce-IT PDUFA / AdComm
It is not a questionable product it is reducing TG. FDA new viewpoint challenging all TG lowering products (not only Vascepa)
Fully agree w how u see the problem: according FDA the science changed. However - as we know - they never informed AMRN about it and they accepted the SPA (as it is) for review in 2013.
The problem that FDA not challenging that for whom (w statin, etc.) but challenging that TG reduction in necessary or not to reduce CVE.
This label is still Trig reduction and not CVE reduction
I is true, however the question is not w/wout statin, but for what: reduce CVE or TG
As I view FDA request 3 things in ANCHOR:
1.) primary eps
2.) secondary eps
3.) ongoing R-IT
and the ANCHOR is not for reduce CVE, but reduce TG. Amarin met with all requirements, however FDA changed the point 3.) to compeleted R-IT. I do not say fine, but OK, However how? They have to follow some regulation, at least inform the sponsor in written format and not by the AdCom BD suggestion.
So, it could be one of the following:
1.) FDA did not follow own rules and regulations
2.) Amarin received the notification, but did not release it.
Amarin has to issue a PR to clarify the situation.
"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."
Now they need the fact ... no comment.
I still do not understand why: no. What is the worst case for FDA: Vascape does not have any effect of CV (btw: they did not say this), best case: it has ... so why not grant?
Vascepa (icosapent ethyl) is indicated as an adjunct to diet and exercise and in combination with a statin to reduce triglyceride TG, non-HDL-C, ApoB, LDL-C, TC, and VLDL-C in adult patients with mixed dyslipidemia and CHD or a CHD risk equivalent.
I agree w u. Revised my previous outlook:
10/16 AdComm: 100% yes ( 0% unanimous)
12/20 Anchor: approved
As I see:
10/11: AdCom material - no suprise
10/13-16: Shutdown over & Debt Ceiling increase aproved
10/16: AdCom - 100% as yes (and 80% as unanimous)
10/25 - 11/03: golden cross
11/04: 10Q (EPS: -0,25 / -0,24)
12/20: PDUFA - 100% as approved
Partnership:
11/15 - 12/20: 50%
12/20 - 01/15: 75%
BO:
- 12/20: 10%
12/20 -: 45%
Golden cross will be around EOM / before 10Q