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I think I'll talk to Amarin first then supply the info....sorry;)
Yup, after the markets closed.
Insight to which way the FDA is leaning, is that cool?
Who wants to see something cool? Is the AH done yet?
Do you have his contact info?
Yes, that's the damage calculator.
Ad Com was sited as reason to hault patent '699. This is absolutely criminal activity!!
I can't believe this is actually happening:(
Williams
Agree...I'm thinking leadership at the FDA is figuring out how this mess ever occurred.
REDUCEIT is at 6000 patients and 200 events. Quarterly meetings review the data and recommend either to continue or stop study.... Those slides are now available with the Ad Con ( pun intended).
I think the FDA wants a peak at the early data, is this an attempt to force the REDUCEIT steering committees hand? That would be horrible science...yet perhaps Amarin's only choice?
The panel wasn't giving FDA safety data and tip footed around the concept when questioned...until finally Eric Coleman conceded that the FDA thought Vasceps was safe. Yet he voting question ask committe to consider safety. It's just plan incompetence and I believe that would be the committees opinion if they has the ball to state the truth. Discussing these matter does nothing...we need to get our message out to the media. Some educated media outlet needs to listen to the Ad Com.
Office of Regulatory Policy ,
Make sure you email the Bloomberg Writer to give your impression of the FDA's Ad Com.
The FDA set the tone they where breaking SPA agreement, tanked the stock....or whatever your view is she's fishing for more...please give it to her.
http://www.bloomberg.com/news/2013-10-22/amarin-cuts-staff-after-fda-panel-scraps-fish-oil-pill-expansion.html?cmpid=yhoo
Don't give her crap! Give her facts!!!!
Like:
19.2% reduction of VLDL.
Very-low-density lipoprotein (VLDL) cholesterol is a type of lipoprotein. Although you may hear about VLDL, your VLDL level usually isn't reported to you as a part of a routine cholesterol screen.
There are several types of cholesterol, each made up of lipoproteins and fats. Each type of lipoprotein contains a mixture of cholesterol, protein and a type of fat (triglyceride), but in varying amounts.
Of the lipoprotein types, VLDL contains the highest amount of triglyceride. Because it contains a high level of triglyceride, having a high VLDL level means you may have an increased risk of coronary artery disease, which can lead to a heart attack or stroke. Higher amounts and large VLDL particles are also associated with an increased risk of high blood pressure and stroke.
There's no simple, direct way to measure VLDL cholesterol, which is why it's normally not mentioned during a routine cholesterol screening. VLDL cholesterol is usually estimated as a percentage of your triglyceride value. A normal VLDL cholesterol level is between 5 and 30 milligrams per deciliter
Go to work team!
Longs please read #2
As a stated in post #18686 (read the document, it's short)
The Ad Com tone wasn't approved by ORP in my opinion, thus it had to contain both #1 & #2 caution statement.
Beyond this:
The FDA openly discussed canceling SPA, this is a violation of "new" policy
The FDA disclaimed, Vascepa was not a NME when discussing why they didn't provide safety data.
I called multiple FDA channels yesterday requesting minutes be posted...hasn't happened yet but we do have audio.
Can anyone make a written document of:
1) the SPA discussion
2) the request to change question
3) leading up to and following the "NME" slip?
The Ad Com as a whole was materially damaging to Amarin, and violated numerous FDA policy's.
Investors with either option losses, or margin calls should initiate action immediatly. Longs can only hope the FDA hasn't permanently damaged company....
Investors should start to look at legal recourse towards FDA ASAP!
Longs please read:
As a stated in post #18686
The FDA really F'd this up. The Ad Com tone wasn't approved by ORP in my opinion.
Read the new policy. Amarin's briefing docs contained both cautionary statements the FDA hoped to cover.
However, the general discussion and tone indicated the FDA was reneging SPA. Obviously set off shock waves as the stock crashed, investors margins got called, and the company laid off half of it's sales force.
Investors should start to look at legal recourse towards FDA ASAP!
FDA attempting to cover legal butt, new guidance today posted:
http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/UCM078816.pdf
100% agree, should get a study going.
JL I'm guessing the Ad Com minutes never get posted for legal reasons. Anyone request the yet through FOI act?
Amarin must open new front, apply for Over the Counter for 500 to 2000 mg Vascepa...sign OTC marketing deal now.
Use NSAID model.
1) Media attention
2) Raises immediate funds for operations
3) Leave Pharmaceutical grade 4 gram dose for REDUCEIT
Urge them do do it last Wednesday....I hope they go for it.
I believe Ad Com was official announcement of intent to breach SPA.
This should be followed up by the written notice.
Note Amarin took down investor Q & A for REDUCIT having to be complete.
We need to sign an OTO partner now!
I'll call the press number tomorrow, and fill them in on the Ad Com.
Treating Trigs to below 150 mg/dl in DM2 with moderate and high risk for CV dz.
Amarin should request Anchor label be lowered to 150 to match guidelines and prevent confusion.
Keep spreading your message, thanks
Williams
Here:
If was probably an internal Amarin doc circulated to employees, it's history and we need to focus on the future. Some of the graphs with the doc didn't copy.
--------
Day 74 Letter-Vascepa-Anchor sNDA
"a note from CITI today : "Standard 74 day letter appears very clean and appears even cleaner that that received for the MARINE filing. The FDA's Day 74 letter is where the agency communicates any initial filing review issues and preliminary plans to hold a Advisory Comm meeting"
From
http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm127153.htm
Filing Review Notification (74-Day Letter)
FDA evaluates the application within the first 60 days of its receipt to determine if it is sufficiently complete toconduct a full review. If FDA determines that the application can be filed (i.e., the application is sufficiently complete), the application review continues. Under PDUFA III, FDA agreed to communicate to applicants any significant review deficiencies identified during the filing review by day 74 of the review cycle. Sending the Filing Review Notification was also specified as an activity in the Filing Review phase of the GRMPs. FDA considers the Filing Review Notification, commonly referred to as the 74-Day Letter, a preliminary review. FDA does not consider this review to be comprehensive nor indicative of deficiencies that may be identified later in the review cycle [12]. Similarly, FDA may not necessarily communicate deficiencies previously identified prior to the Filing Review (e.g., issues previously communicated during EOP2 or Pre-NDA/BLA meetings).
The 74-Day Letter was implemented to comply with PDUFA III goals in early 2003[13] (Exhibit 20). The 74-Day Letter was evaluated for effectiveness as a tool to provide earlier communication of issues to sponsors.
So if Citi said they had seen the letter and it was clean as a whistle, ANCHOR Adcom should be easy-peasy just as we suspected.
*Chairman said that the SPA was put in place in 2008 and landscape has changed since then. Many outcomes studies, ACCORD, AIM-HIGH, HPS-THRIVE etc. failed. If the outcomes with these trials were different then the tone of this ADCOM meeting would be very different.
*FDA had many opportunities to revisit any issue regarding the SPA filed in 2008 prior to the ADCOM:
?#1 When the ANCHOR safety was added to MARINE PI
?#2 During ANCHOR sNDA filing
?#3 Around/During the filing of the 74 day letter to Amarin
?#4 During the announcement to Amarin that the FDA would hold an ADCOM meeting
General Communication (From FDA Website)
The FDA and sponsors frequently engage in informal communications (e.g., email, telephone, and fax) in addition to face-to-face meetings during review of a product application. Sponsors generally contact FDA to determine the status of their product’s review or to respond to an information request while FDA contacts sponsors to request critical information and provide sponsors with opportunities to justify their findings and conclusions.
Exhibit 24. FDA-Sponsor Communications for FY2005-FY2007 Cohort
Analysis of Action Packages and FDA systems revealed that the frequency of FDA-sponsor communications was similar for single-cycle and multi-cycle reviews for the first three-quarters of the cycle (Exhibit 24). However, in the final quarter of the review cycle, there was a significant increase in communications for single-cycle approvals compared to multiple-cycle applications. Approximately 70% of these additional communications were related to labeling and PMC issues, suggesting that likelihood of approval drives the additional communications, rather than the reverse. This pattern was similar for both Standard and Priority review applications.
Further analysis of the FDA-sponsor communications showed that the overwhelming majority of communications used teleconference or written formats (Exhibit 25). According to an FDA guidance, FDA minimizes the use of resource-intensive face-to-face meetings during the review, which are instead reserved for products with specific issues as outlined in the relevant guidance.
Postmarketing Study Commitments
Postmarketing study commitments (PMCs), also referred to as Phase 4 commitments, are studies that are conducted by a sponsor after FDA has approved a product for marketing. FDA requires PMCs for products in certain situations, such as those approved under the accelerated approval provision, based on animal efficacy data, or not sufficiently labeled for pediatric use [17].
Exhibit 34. Products with Postmarketing Study Commitments in FY2002-FY2007 Cohort
Agreed-upon PMCs are intended to further characterize the safety, efficacy, or optimal use of a product, or to ensure consistency and reliability of product quality. Agreed-Upon PMCs can be used to resolve important issues that do not override the determination that the product is effective and safe for marketing. For the FY2002-FY2007 cohort products, nearly the same proportion of single-cycle (86%) and multi-cycle (84%) applications were approved with PMCs (Exhibit 34). While the percentage of applications with PMCs was similar between single and multi-cycle, there was a significant difference in the number of PMCs assigned.
Exhibit 35: Distribution of PMCs for Single- and Multi-Cycle Approvals
The average number of PMCs associated with applications that had PMCs was significantly different for single (7.5) and multiple cycle (4.4) review products (Exhibit 35). This difference was primarily due to a greater number of required and CMC PMCs associated with single-cycle applications. There were a similar number of agreed-upon PMCs for single (5.4) and multiple (4.6) cycle review applications. [18].
Exhibit 36 shows that the greatest proportion of PMCs are related to CMC issues (24%), followed by clinical safety (21%), clinical efficacy (16%) and clinical pharmacology (15%). A new clinical study request constituted 51% of PMCs. A detailed analysis of agreed-upon PMCs and their associated development and tracking processes was conducted in a separate study commissioned by FDA and completed in 2007.
*Most diabetes products have been approved by the PDUFA date either with or without PMC’s. With the safety and efficacy of Vascepa doesn’t it make sense to approve for ANCHOR and allow Reduce-It to be a PMC? That is how the SPA was set up.
Q2 Earnings Report
The Day 74 letter for the ANCHOR sNDA included no such surprises. In particular, the letter did not in any way suggest that the agency plans to reset its requirement for approval of the ANCHOR indication. Some investors have interpreted the AdCom as implying that the agency intends to change the rules for Amarin with respect to the status of the REDUCE-IT outcome study. We have not seen evidence of such a change. We had considerable discussion with the agency over what constituted substantially underway for the outcome study. And during these discussions, never did they suggest changing their requirements.
Rather we believe that they appreciate the broad undertaking that we are pursuing with REDUCE-IT and the scientific seriousness with which we are conducting the study. At this point, FDA has accepted our sNDA for review, which reflects to us that they agree that the outcome study is substantially underway. While we believe we do not need the REDUCE-IT study to be completed for approval of the ANCHOR indication, we do believe that this study is positioned for success. Highly pure-EPA in the JELIS study -- Japanese population demonstrated significant reduction in cardiovascular events over statin therapy alone.
Some investors argue that because the AIM-HIGH study with Niacin that the FDA will change it's view on Vascepa . As a reminder Niacin is an HPL raising drug not a triglyceride lowering drug and Niacin remains approved on the market. Some also argue that fenofibrate FIELD outcome study and this will have a bearing on getting the FDA to reassess its requirements for Vascepa . Fenofibrates were not directly studied in a patient population with alleviated triglycerides in an outcome setting.
In fact, an Accord study of fenofibrate the subgroup of patients who had alleviated baseline triglycerides showed improved outcomes. This has not been widely publicized because this was not the pre-specified primary endpoint of the study and the study was not powered for this purpose, but it is supportive of the value of lowering triglyceride levels in patients with high triglycerides. In addition, Vascepa not only lowers triglycerides but lowers distraction of other lipid parameters including compared to placebo LDL-C a well established marker of outcomes and Vascepa also lowered various other inflammatory biomarkers.
Vascepa does this with a safety profile which is comparable to placebo. Today, patients with alleviated triglycerides are being treated on-label or off-label with the variety of drugs which increase LDL or have various other side effects. We find it difficult to believe that given this environment and the safety and efficacy profile of Vascepa that Vascepa won't be approved for this expanded indication.
It is of course important to note that we do not yet know the focus of FDA and the AdCom panel. Our comments today reflect our recent assessment as the issues that will be presented and our view of our planned responses and readiness to address anticipated lines of enquiry. We will continue to access potential topics and plan accordingly as we continue to prepare for and look forward to the AdCom on October 16th.
I gave it to him.
JL
Of special importance is a recent decision from the federal courts that says the FDA can not prevent a drug from listing benefits unless the FDA can prove that the information is false or misleading..At present time there is no impediment to AMRN advertising Vascepa (EPA) has been shown to lower insulin resistance in diabetics (the crucial thing)..or that EPA has been shown to improve CVD event outcomes in certain types of lipid abnormalities, and that EPA lowers inflammatory markers and this suggests it might be effective in atherosclerosis..
If my red neck legal degree read this correctly, Amarin could use AACE guidelines as a Marketing Tool.
Anyway to get a statement from Physicians urging the FDA not to end surrogate markers for drug development in the DM 2 population? It would cover lipid and new DM 2 blood sugar drugs recently approved or in process.
Poised & Focussed, don't shake arms...check, take of tinfoil hat?
LOL
I can talk to Ms. Behr, CDER Ombudsman.
FDA Director of CDER 2, he was at the Ad Com.
Looking at the SPA guidance I do believe he would be making the decision to break the SPA.
1)Director of CDER 2
301-796-2310
email curtis.rosebraugh@fda.hhs.gov
organization DHHS/FDA/CDER/OMPT/CDER/OND/ODEII
fax 301-796-9717
building WO22
room 3214
station Silver Spring MD 20993-0002
2)CDER Ombudsman
I have her contact information, and I'm trying to set a meeting with her, we have had dialogue for over a year r/t NCE
3)CDER Policy & Legal
I'm willing to covey our message to CDER Ombudsman.
Please advise.
Williams
Monday I'm faxing Dr. Curtis Rosebraugh the 2013 AACE guidelines, any thing else I should include?
I agree, in fact, many stated efficacious results for 200-500 Trigs and the Chairman did get in his confidence on safety. It was a very strange Ad Com.
The Director for Vascepa review is Dr. Curtis Rosebraugh, read his review of the following for a diabetic drug.
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM226068.pdf
Looking at this SPA guidance again:
"The key statement here is "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." If Bruno is being truthful- this requirement did not happen. FDA is in clear violation of their binding regulation."
The director of the division would be making the decision, not the FDA. Would this make CDER Director the target of Litigation?
Breaking the SPA due to "substantial" change in scientific knowledge is a huge stretch. In light of the new 2013 Guidelines would be plan stupid.
The individual would be taken to court under: Federal Tort Claims Act
http://en.wikipedia.org/wiki/Federal_Tort_Claims_Act
Amarin longs please read:
The FDA appears to be moving towards ending surrogate endpoints. We need the help of Big Pharma and we need it NOW!
http://www.bioworld.com/content/emdac-asks-cardiovascular-outcomes-amarin’s-vascepa
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee broke with the recent track record of the agency in recommending against an application for a lipid-lowering agent based on a surrogate endpoint, asking instead for results of an ongoing cardiovascular outcomes trial before recommending approval.
Most drugs on the market today are approved with surrogate markers, including ALL the new diabetes medications. Despite the drop in HgbA1c we are still seeing the same or rising CV deaths in type 2 DM patients. Reducing HgbA1c is a surrogate marker it's not a direct marker for CV disease. Yet we use it to approve drugs to decrease the risk of CV disease.
Amarin is using the wrong placebo! We must find out what's killing these people, Diabetes or inflamational risk factors that Vascepa treats.
First, me must present the idea to all recently approve DM2/1 Big Pharma drug companies. This is the start of the FDA pulling surrogate markers and Voided a successful SPA study. It is the destruction of innovation and venture capital investing in Pharma.
Amarin has to contact their past Big Pharma Executives , we must get a petition signed by Big Pharma leaders requesting the FDA not to end surrogate markers and void SPA agreements.
This is where we start:
The science doesn't prove reducing HbgA1c reduces CV events, we use HbgA1c as a surrogate to measure efficacy. Most CV events occurred in persons with MODERATELY elevated HbA1c.
"The risk for cardiovascular disease and total mortality associated with hemoglobin A1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A1c concentrations in persons without diabetes."
In no way am I suggesting a campaign to bash these drugs, ending surrogate markers in the type 2 DM patients will end innovation to help reduce their 4 fold risk at cardiovascular events.
Next all recently approved DM meds:
Byetta, Symlin, Januvia, Victoza, Bydureon, Tradjenta and Onglyza.
Companies:
AMYLIN. Byetta
BMS and AZN. Symlin
I don't have time to list them all.
Someone who can articulate this message please start on a statement we can get signed by these company CEO's and send to the FDA. Ending surrogate markers in an extremely high risk population is destructed to the innovation we are attempting to save lives.
Please
Thoughts?
Williams
Joe and I talked about the briefing doc... I'm not going to talk for Amarin, call them if you have a question.
I called Joe Bruno and left a very specific message, he called me back. Amarin has not been contacted by the FDA in regards to breaking the Anchor SPA agreement...ever.
The FDA took a huge crap in the pool when suggesting they might not abide by SPA.
Correct, to my knowledge Amarin has not been notified of any breach. This was yesterday around 5PM, from Joe Bruno.
In addition to the sell off they have damage the entire drug industry, venture capitalist are fleeing like rats from a sinking ship.
My thoughts also. However, the FDA indicated at the Ad Com, they would like to use other drugs phase 3 results (That treated normal Trig levels) to judge a completely separate class of drug under going an outcomes on high Trigs.
Big Pharm needs to step in, voiding Amarin's SPA prohibits future funding of any drug develop program.
First the FDA hasn't contacted Amarin about Anchor SPA. It would have be prudent to do so before accepting sNDA in February. At that time they could have negotiated and fulfilled any requests made by the FDA.
By accepting the sNDA, the FDA indicated (to the investing World that read SPA guidance) they where satisfied by the agreement. All failed Phase 3 of other Trig lowering drugs validate the New AACE 2013 guidelines of Trigs> 150 appears to a statistically safe level. These studies failed because average Trigs were already too low. This was covered in Ad Com.
Amarin received a negative vote because the focus was on safety, the FDA was outright negligent not to provide their assessment of safety. They could have simply provided the safety data from Marine review contain on their Website. Here: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057_vascepa_toc.cfm
Non of the Ad Com committee could accurately vote on approval without a risk/benefit judgement. You can tell none of the FDA docs prescribe, or give drugs. I would never give a drug that I didn't have a safety judgement on.
Second, committee had a majority that admitted Trig 200-500 efficacy. This precluded the FDA using the Ad Com as cover for efficacy.
Eric Coleman, after Dr. Hiatt pushed the issue, finally gave into Amarin's safety. However, this was late and after the safety of Amarin was dragged through the mud. There was no recovery at this point.
The FDA has no legal cover to revoke SPA. I believe this was there primary reason for the Ad Com.
Amarin should request AACE lipid guidelines on label, ASAP.
Calculating a hazard ratio, using adjudicated Trigs > 200, shows a significant drop in CV events.
Using a population of 70,000,000 with at risk Trig level, amounts to a potential reduction in CV events of 1.2 million per year. Very, very conservative. This translates into Billions of saved health care dollars and lives.
Risk is placebo equal.
The FDA approves drugs that show an increase in CV events!
http://www.medicinenet.com/script/main/art.asp?articlekey=173225
http://m.huffpost.com/us/entry/3854510
But specifically this drug. In the safety review document, the cardiac Hazard ratio was much higher than the FDA was going to tolerate. Nonetheless, approval with post marketing study that will likely show an increase in CV events.
http://www.cbc.ca/m/touch/health/story/1.1365168
I will request every drug with a CV risk be taken off the market in a CP quoting reviewers dating back to Vioxx.
http://www.vioxxsettlement.com
LOL!!! The FDA has not ruled. The only, AND I MEAN ONLY way is Vascepa 150-500. Amarin tried to knock it out of the park but it went foul. SPA is binding and Amarin has not been notified the FDA intends to breach the regulatory document. Those that sold today where foolish to not DD SPA.
Chab, the AACE recommends "AGRESSIVE" treat for those DM 2 patients that have had an event to a Trig level of under 150! Not 200! Read the document in full. They caution against DHA that could raise LDL!
I fed this to you people weeks ago! Run, spread the news! 150 is the guideline not 200!
The FDA can ONLY break SPA agreement for SAFETY (Not presented by the FDA!) or change in clinical efficacy ??...!
They have neither!
FDA Coleman gave his safety blessing statement.
AACE gave guideline.
Both are written documents admissible in a court of law.
The FDA gave Amarin no indication of wanting to break SPA, this means they don't intend to break SPA. They have to follow guidance, those that sold got screwed....including the dumb HF that should pay me millions to consults for them. December 20 th. Amarin needs to negotiate label...I suggest they recommend whatever the AACE feels comfortable with.
150!!!!! Not 200!!!!