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Looking at the Lovaza Citizens Petition, the FDA sent an acknowledgement letter to Crowell Moring with a docket # the same day the CP was received. I am not aware of anybody stating the FDA has acknowledged the CP. I emailed the FDA to verify whether or not they have received a Vascepa CP and what the docket # is.
Hopefully they do not use this "delay" as a reason to go ahead and ignore prior to 12-20. We will see.
zumantu,
It looks as if the FDA is not acknowledging receipt of the Vascepa Citizens Petition as of 12-13-2013.
FDA CP Tracker
Now all we need is management taking one for the team and announcing a reduced salary for awhile. Show your investors that until they are made whole, management too will take a pay cut.
very good letter but your first sentence needs to be changed...
We are very concerned that the FDA is not serving the public interest in an irrational, unfair, and harmful way.
Either the fda is serving the public this way or you are concerned that the FDA is not serving the public interest in a rational, fair, and harmless way.
Found on yahoo.....interesting!
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the lawsuits are fairly common for sure....you ever been contacted by a lawyer after an accident? Competency can be questioned with this management, fraudulent they are not. From their August 8th financial report...
"These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties.... In particular, Among the factors that could cause actual results to differ materially from those described or projected herein include the following: uncertainties associated generally with research and development, clinical trials and related regulatory approvals; the risk that Special Protocol Assessment agreements with the FDA are not a guarantee that FDA will approve a product candidate upon submission"
End of story!
well if the lawyers accused 'em, hang 'em..... ambulance chasers at it's finest.
Zumantu,
Very good idea. Have you contacted the Epa Drug Initiative with this? Email them with this.
Wasn't much coverage of the Open letter press release. How to change that?
EPA Drug Initiative Open Letter to FDA Commissioner Hamburg
December 12, 2013
The U.S. Department of Health and Human Services
200 Independence Avenue, S.W.
Washington, D.C. 20201
Dear Dr. Hamburg:
We are writing to request that you personally intervene in the FDA’s recent decision to rescind the ANCHOR SPA agreement with Amarin Corp and we ask you overturn this unjust decision.
Background:
On October 29th, 2013, in a highly controversial move, the FDA reviewing division rescinded the special protocol assessment (SPA) with the Amarin Corporation in relation to the application for the use of Vascepa for lowering triglyceride (TG) in patients with high TG level (200-500 mg/dl) with mixed dyslipidemia. (Vascepa had already been approved for lowering TG in patients with very high TG level = 500 mg/dl.) The reviewing division stated that the decision to rescind the ANCHOR SPA was based on the 3 recently completed outcome trials (ACCORD-Lipid, AIM-HIGH, HPS2-THRIVE) and erroneously concluded TG lowering in patients with high TG levels (200-500 mg/dl) would not be clinically beneficial.
As the ANCHOR trial fulfilled all aspects of ANCHOR SPA, including a safety profile equal to placebo, the only mechanism available for the FDA to deny approval was to use the “substantial new scientific issue” argument. In taking such an unprecedented action, the reviewing division completely ignored the basic tenets of sound scientific review and made an extreme, leap-of-faith extrapolation to conclude that TG lowering in patients with high TG (200-500 mg/dl) would not have clinical benefit. The conclusion of the reviewing division is not supported by the clinical data and the actions taken to rescind the SPA are then baseless and without any scientific merit.
Discussion:
The FDA reviewing division’s use of the 3 outcome trials to somehow demonstrate that TG lowering therapy does not benefit patients with high TG levels (200-500 mg/dl) is fundamentally flawed and contradicted by the study results. The three major reasons are as follows:
1) The drugs used in each of the referenced trials were very different compounds (fenofibrates and niacin) from Vascepa and had distinct mechanisms of action and effects on lipid levels (e.g. fenofibrates lower TG but raise LDL-cholesterol while Vascepa lowers both TG and LDL-cholesterol).
2) None of the three trials were designed or statistically-powered to study the TG lowering effects in high TG population, and most of the patients in the trials had either normal or borderline TG levels; thus the trials simply could not inform whether TG lowering effects would be clinically beneficial in patients with high TG levels.
3) The sub-group analysis of the trials based on TG levels indicated that patients with high TG (= 200 mg/dl) and low HDL-cholesterol, (the patient sub-population covered by the ANCHOR SPA), had an impressive reduction in cardiovascular disease (CVD) risks of 28 and 37%, prompting the investigators to conclude that these “patients likely benefited from TG lowering therapy.”
There is no scientific evidence to support the FDA reviewing division’s conclusion that these trials somehow indicate that TG lowering will not improve clinical outcome in patients with high TG levels. Therefore, the decision to rescind the ANCHOR SPA has no valid scientific justification. In fact, the outcomes results suggests the contrary; that TG lowering therapy may be highly beneficial in the ANCHOR sub-population.
Approximately 800,000 Americans die of heart disease each year with roughly 715,000 Americans experiencing a heart attack, or one every 44 seconds. Besides the personal impact and burden CVD puts on American families, this health epidemic carries an economic burden of enormous proportions. It is estimated that over $300 billion will be spent in the U.S. this year treating CVD, and that number is projected to grow to around $830 billion by 2030. The financial cost of CVD is a tremendous economic strain to the continually rising health care expenses. Although the new AHA/ACC guidelines focus mainly on the role of statins in lowering LDL-cholesterol, it is well established that the statins only lower CVD risk by 30 % and significant residual CVD risk persists. Many patients, despite being on statin therapy, continue to have high TG levels. Recent meta-analysis studies demonstrated that each 10 mg/dl rise in TG level predicts a 1.4 % increase in CVD risk. Thus, treating high TG level (= 200 mg/dl) is potentially important adjunctive therapy to statins to further lower the CVD risk.
Vascepa is an ultra-pure eicosapentaenoic acid (EPA) (an omega-3 fatty acid) that has been shown to be highly efficacious in lowering TG when added to statin therapy. In the only large outcomes trial of ultra-pure EPA, when given in combination with statins, there was an overall 19 % reduction in CVD events. Patients with high TG and low HDL (ANCHOR sub-population) had a remarkable 53 % reduction in CVD events, confirming that pure EPA reduces CVD risks and saves lives in patients with high TG levels. While a clinical outcome trial with Vascepa called REDUCE-IT is currently underway, it won't be completed until 2017, or later. Waiting 4 years is far too much to ask of millions of Americans who will pay not only with deteriorated health, but many are likely to die needlessly.
The FDA routinely makes difficult decisions pertaining to drugs in terms of weighing therapeutic benefit against the risk of serious side effects. Given its excellent safety profile and efficacy, the risk-to-benefit considerations clearly favor Vascepa approval.
Conclusions:
The FDA decision to rescind the ANCHOR SPA is simply not supported by the evidence cited by the reviewing division. The reviewing division made a serious error in extrapolating that the lack of clinical benefit by fenofibrates and niacin therapy in patients with mostly normal and borderline TG levels somehow demonstrates that Vascepa would not have clinical benefit in patients with high TG levels, the ANCHOR population. In direct contradiction to the FDA reviewing division’s assertion, the sub-group analyses from these trials indicated that patients with high TG and low HDL had a remarkable reduction in CVD events of 28 % (ACCORD-Lipid), 37 % (AIM-HIGH), and 53 % (JELIS), clearly supporting a therapeutic benefit in ANCHOR sub-population.
We urge you to intervene in this important matter and take actions to overturn the reviewing division’s decision to rescind the ANCHOR SPA. For unclear reasons, the FDA reviewing division is going to great lengths to deny Vascepa for lowering TG in patients with high TG levels and mixed dyslipidemia, even if it means that they have to rely on flawed analysis. We respectfully request that the FDA make this important drug available without undue delay. We admire your integrity and your outstanding track record of compassion and dedication to improving medical care to the underserved, we remain very hopeful that you will investigate this matter fully and fairly, and conclude that the reviewing division erred in its review and that the decision to rescind the ANCOR SPA was unjust.
Kind regards and on behalf of many,
The EPA Drug Initiative
Taken from their website....
The members of King & Spalding’s Government Advocacy & Public Policy (GAPP) practice provide a full range of services to assist our clients in managing their interactions with the federal government. With government activity reaching into more areas of our clients’ business than at any time in recent memory, our government relations team works with clients to develop and implement strategies to maximize opportunities, minimize risks, and accomplish their strategic goals.
Amarin hires Lobby Firm.
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Issues related to patient access to emerging heart disease medications
Reply to Senator Stabenow-MI
Senator Stabenow,
The FDA is ignoring their own rules when it comes to Amarin Corp. and it's drug Vascepa. It has been ruled by the FDA a safe drug, comparable to a placebo. This issue is with how the FDA has determined it's efficacy. You know very well that no legislation will come before you in the Senate regarding the FDA anytime soon. In the meantime, while you wait for legislation, thousands of American lives will be lost that possibly could have been saved and the FDA and others in a position to correct this wrong will have to live with the choices they made or didn't make. Please read the following, look at the supporting EPA studies attachment and ask yourself if what the FDA is doing seems logical.
FDA's Possible Unethical Treatment of Amarin Corp
The FDA has a well documented history of unethical behavior and conflicts of interest. In July of 2012, Senator Grassley wrote the FDA questioning the agencies behaviors towards it's own employess who had contacted Congress about unethical behaviors within the FDA. In this letter, Senator Grassley stated, "FDA's misconduct cannot be ignored." Unfortunately we find ourselves questioning the FDA's conduct again. The facts to be presented show clear and concerning misconduct and unethical behavior by the FDA towards Amarin Corp and it's drug Vascepa. The decisions the FDA have made, or refused to make, have become alarmingly inconsistent. Congress enacted SPA provision and the FDA Modernization Act of 1997 to eliminate what was known as the moving target syndrome or repeated changes in FDA’s advice about studies needed to obtain FDA approval. Congress needs to open an investigation to sustain public confidence in, and to reinforce an open and transparent decision making process by the FDA, free of unethical behavior and conflicts of interest.
If you are not aware, Amarin Corp. is studying the effects of EPA on lipid profiles and has an approved drug called Vascepa. Vascepa significantly reduced the TG levels and improved other lipid parameters without significantly increasing the LDL cholesterol levels. Heart attacks, strokes and other cardiovascular events represent the leading cause of death and disability among men and women in western societies. According to the American Heart Association's 2010 At-A-Glance Report, over 831,000 deaths in the United States were caused by heart disease and stroke, substantially more than the approximately 572,000 reported deaths caused by cancer. (American Cancer Society. Cancer Facts & Figures 2011. Atlanta: American Cancer Society, 2011)
FACTS
1.The FDA failed to honor an SPA (Special Protocal Assessment) agreement and later reneged on this agreement to justify it's position.
The FDA approved Vascepa, as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (TG greater than or equal to 500mg/dL) hypertriglyceridemia (very high triglycerides), in July of 2011. In February of this year, Amarin submitted an sNDA (Supplemental New Drug Application), seeking approval for the marketing and sale of Vascepa (icosapent ethyl) capsules for use as an adjunct to diet in the treatment of adult patients with high triglycerides (TG =200 mg/dL and < 500 mg/dL) with mixed dyslipidemia. As part of the agreement with the FDA, Amarin was required to conduct a 12 week efficacy study (Anchor) and substantially enroll a cardiovascular study. Amarin met all obligations set by the SPA agreement with the FDA. On October 16th, the FDA held an AdCom meeting to discuss the efficacy of Vascepa. At this AdCom, the FDA explicitly questioned the efficacy of whether reducing triglycerides in the Anchor Indication would have a positive effect on coronary heart disease or its risk equivalent. Keep in mind that Amarin and the FDA, as part of the Anchor sNDA approval, entered into a SPA (Special Protocol Assessment) agreement for the design of a cardiovascular outcomes study of Vascepa formally titled REDUCE-IT (Reduction of Cardiovascular Events with EPA - Intervention Trial) to answer that exact question. The FDA, with these agreements, led Amarin to believe that once REDUCE-IT was substantially underway, the Company would have met all of the requirements to request approval of Vascepa for treating the mixed dyslipidemia patient population studied in the ANCHOR trial.
Shortly after the AdCom, the FDA rescinded the Anchor SPA, as it had determined that a substantial scientific issue essential to determining the effectiveness of Vascepa in the studied population was identified after testing began. The FDA questioned the efficacy of Vascepa, citing the outcomes results of three studies, (Accord-Lipid, Aim-High and HPS2-Thrive), which according to the FDA failed to support the hypothesis that a triglyceride-lowering drug significantly reduces the risk for cardiovascular events among statin-treated patients with mixed dyslipidemia and residually high serum triglyceride levels (200-499 mg/dL). Because the results of all three of these studies were available to the FDA when Amarin agreed to amend the SPA for the REDUCE-IT study and because these concerns were not raised to Amarin in connection with the FDAs acceptance for review of the sNDA for ANCHOR or at anytime prior to the October 16 AdCom, the FDA failed to timely notify Amarin of these new issues. According to the FDA, "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 (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". There was no mention of this change at any point leading up to the AdCom including the sNDA acceptance letter (Day 74 Letter) for ANCHOR or at any time prior to the AdCom, even though the majority of this outcomes data was available for some time.
2. The studies used by the FDA do not provide substantially new scientific information
The Three studies used by the FDA to question the efficacy of Vascepa were not an apples to apples comparison and should not be used to invalidate the efficacy of Vascepa. The three studies (Accord-Lipid, Aim-High and HPS2-Thrive), did not use the same class of drugs, nor did they involve the patient population Amarin seeks to treat. All three studies, according to the FDA, failed to prove a significant reduction in cardiovascular events. However, all three studies involved patients with triglyceride levels far below that which Vascepa is intended for. None of those outcome studies prospectively enrolled patients who had elevated triglycerides in spite of statin control with LDL cholesterol. In ACCORD, which was a Fenofibrate study, the mean triglyceride level in the overall study was just 162 mg/dL. In the Aim-High, which was a Niacin study, the median triglycerides levels were 161 mg/dL. In HPS2-Thrive, another niacin study, the mean triglycerides were 1.43(0.84) mmol/L. Not one of these studies investigated reduction of triglyceride levels in the 200-500 mg/dL range which Amarin sought approval for. ACCORD and AIM-HIGH proved nothing other than triglyceride lowering has a neutral outcome effect on people with normal baseline triglyceride levels. With respect to the population studies in the ANCHOR trial, the FDA also appears to have entered into an SPA with another company for their drug after the ACCORD and AIM-HIGH data were publicly presented suggesting that these study results were not viewed by the FDA as substantially new scientific information at that time.
3. The FDA approves Antara (fenofibrate) for the treatment of high cholesterol, mixed dyslipidemian and high
triglycerides and allows fenofibrates to continue this treatment despite failed outcomes studies
On October 22nd, the FDA informed drug maker Lupin Limited (Lupin) that it had received final approval for it's fenofibrate drug Antara to treat patients with high cholesterol, mixed dyslipidemia and high triglycerides. The FDA, six days prior, used the failure of a fenofibrate study (Accord-Lipid) to question the efficacy of Vascepa and used this science to rescind the Anchor SPA agreement. The Accord-Lipid study failed to produce a significant reduction in cardiovascular events, yet Antara was approved to treat this patient population. Just recently the FDA and an AdCom panel voted to continue allowing fenofibrates to be prescribed for this patient population despite the failed outcomes trials. Again, no failed studies exist for Vascepa's efficacy in this patient population.
4. The FDA fails to allow Anchor study information on Marine Label
The FDA has failed to allow Amarin to have the ANCHOR data included in the clinical study section of the Vascepa package insert, yet, not become a formal indication for Vascepa. In doing so, the FDA may force Amarain to seek judicial relief to support their efforts, such as the right to use the ANCHOR data in commercial materials based on pre-commercial speech principles by doing the First Amendment, that protect the ability to communicate truthful information such as clinical trials results. As a comparison, the FDA affords Vascepa competitor Lovaza (GlaxoSmithKline) this exact right, which includes information for add-on therapy of Lovaza with a statin. Keep in mind the FDA rejected this study of co-administration of Lovaza with a statin as Lovaza raised LDL cholesterol. The failure of the FDA to allow Amarin to include the Anchor Indication information which is also a co-administrative treatment with a statin has been detrimental to the sales of Vascepa as sales representatives are prohibited in providing the information.
5. The FDA fails to provide Vascepa with an exclusivity designation
Exclusivity designations are made to protect drug makers from generic competition reductions and to create financial incentive for research and development. In 1992, under the Prescription Drug User Act (PDUFA), FDA agreed to specific goals for improving the drug review time and created a two-tiered system of review times – Standard Review and Priority Review. A Priority Review designation means FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review). Vascepa was approved July 26, 2012. Under any timeframe, the FDA has failed to make a ruling to the detriment of Amarin Corp. Additionally, the USPTO requested clarification from the FDA on whether Icosapent Ethyl (Vascepa) had ever been approved prior to July 26, 2013. The FDA failed to respond to the USPTO. Part of the reason for the delay in exclusivity designation was due to a Citizens Petition (known as Lovaza Citizens Petition) filed by John Fuson of Crowell and Moring LLP on February 6, 2013. Mr Fuson, who joined Crowell and Moring LLP May 30, 2012, happened to serve as associate chief counsel at the U.S. Food and Drug Administration (FDA) since 2007, where he worked with the U.S. Department of Justice's Consumer Protection Branch, bringing enforcement actions on behalf of the FDA. The petition was submitted to essentially list Vascepa's active ingredient retroactively for Lovaza, thus preventing NCE for Amarin's Vascepa. Section 505(q)(1)(F) governs the timeframe for final Agency action on a petition. Under this provision, FDA shall take final Agency action on a petition not later than 180 days after the date on which the petition is submitted. The 180-day period is not to be extended for any reason, including any determination made under section 505(q)(1)(A) regarding delay of approval of an application, the submission of comments or supplemental information, or the consent of the petitioner. To date almost 300 days later, a decision has still not been made by the FDA.
6. Sham Citizen Petitions and the anticompetitive effect
In a 95-page decision from the U.S. District Court for the Eastern District of Pennsylvania in In re Wellbutrin XL Antitrust Litigation, the court once again addressed the issues of “sham” citizen petitions, liability under the Sherman Antitrust Act, and Noerr-Pennington immunity. The court previously addressed citizen petitions alleged to be shams in In re Flonase Antitrust Litigation, 795 F. Supp. 2d 300 (E.D. Pa. 2011). When petitioning activity “ostensibly directed toward influencing governmental action[] is a . . . sham to cover what is . . . nothing more than an attempt to interfere directly with the business relationships of a competitor[, then] the application of the Sherman Act would be justified.” Noerr, 365 U.S. at 144. The sham exception requires that a petition be “(i) ‘objectively baseless,’ and (ii) ‘an attempt to interfere directly with the business relationships of a competitor through the use of the governmental process – as opposed to the outcome of that process – as an anticompetitive weapon.’” Primetime 24 Joint Venture v. Nat’l Broad. Co., 219 F.3d 92, 100-01 (quoting Prof’l Real Estate Investors, Inc. v. Columbia Pictures Indus., Inc., 508 U.S. 49, 60 (1993) (“PRE”)). The Lovaza Citizens petition, filed by Crowell & Moring asks "... the Commissioner could adopt a strength for Lovaza based upon the fixed amount of major omega-3-acid ethyl esters specified in the Lovaza reviews and labeling. According to its currently-approved labeling, "at least 900 mg of the ethyl esters of omega-3 fatty acids sourced from fish oils" "are predominantly a combination of ethyl esters of eicosapentaenoic acid (EPA - approximately 465 mg) and docosahexaenoic acid (DHA - approximately 375 mg)." By requesting EPA to be listed retroactively, the petition has created uncertainty and delay in the FDA's exclusivity designation of Vascepa. Lovaza maker GSK has opposed each and every request and recommendations made in the petition. GSK refutes the citizens petition by stating that the entire fish-oil based mixture in Lovaza-not just the ethyl esters of omega-3 fatty acids-constitutes the active ingredients. Because this petition interfered directly with the business relationship of a competitor, it needs to be investigated and determined with whom Crowell and Moring are representing. Unsurprisingly, GSK's drug Lovaza has benefited from this citizens petition.
Senator Stabenow, I've voted for you every election and in return I am asking a favor. I'm asking you to look into this for the underdogs. This company has done all that has been asked by the FDA and on December 20th the FDA will destroy it. The Science of EPA cannot be ignored forever. However, until it is heard, who will be responsible for the thousands of lives lost. The FDA is flat out wrong. I've included a list of supporting EPA documents and studies. Unlike me, you are in a position to get straight answers to your questions. I have emailed the FDA, DOJ, NIH, NHLBI and many others and at most got a form reply back. I'm asking for more, and I hope you will step up and provide this for me. I truly appreciate your reply and hope to hear from you soon.
You make statements like you are involved with FDA decisions. You state EBM's then say policy is not retroactive? You are about as consistent as the FDA. The only failed studies involve niacin and fibrates.....there are no studies that disprove the efficacy of EPA. Why was antara just approved by the FDA?
I'm sorry, but I have to disagree wholeheartedly. If the FDA has changed their policy to EBM, why do they allow fibrates and niacin to be prescribed for this patient population, if the known science states they do not work? Your belief is inconsistent with the FDA's position.
Biochica,
The 2g arm of the study received four pills just like the 4 g arm. The 4 pills were 2 mineral oil pills and the other 2 were 1 g vascepa.
Posted at Yahoo
World Renowned Heart Surgeon Speaks Out On What Really Causes Heart Disease
By: Dr. Dwight Lundell
We physicians with all our training, knowledge and authority often acquire a rather large ego that tends to make it difficult to admit we are wrong. So, here it is. I freely admit to being wrong.. As a heart surgeon with 25 years experience, having performed over 5,000 open-heart surgeries,today is my day to right the wrong with medical and scientific fact.
I trained for many years with other prominent physicians labelled “opinion makers.” Bombarded with scientific literature, continually attending education seminars, we opinion makers insisted heart disease resulted from the simple fact of elevated blood cholesterol.
The only accepted therapy was prescribing medications to lower cholesterol and a diet that severely restricted fat intake. The latter of course we insisted would lower cholesterol and heart disease. Deviations from these recommendations were considered heresy and could quite possibly result in malpractice.
It Is Not Working!
These recommendations are no longer scientifically or morally defensible. The discovery a few years ago that inflammation in the artery wall is the real cause of heart disease is slowly leading to a paradigm shift in how heart disease and other chronic ailments will be treated.
The long-established dietary recommendations have created epidemics of obesity and diabetes, the consequences of which dwarf any historical plague in terms of mortality, human suffering and dire economic consequences.
Despite the fact that 25% of the population takes expensive statin medications and despite the fact we have reduced the fat content of our diets, more Americans will die this year of heart disease than ever before.
Statistics from the American Heart Association show that 75 million Americans currently suffer from heart disease, 20 million have diabetes and 57 million have pre-diabetes. These disorders are affecting younger and younger people in greater numbers every year.
Simply stated, without inflammation being present in the body, there is no way that cholesterol would accumulate in the wall of the blood vessel and cause heart disease and strokes. Without inflammation, cholesterol would move freely throughout the body as nature intended. It is inflammation that causes cholesterol to become trapped.
Inflammation is not complicated — it is quite simply your body’s natural defence to a foreign invader such as a bacteria, toxin or virus. The cycle of inflammation is perfect in how it protects your body from these bacterial and viral invaders. However, if we chronically expose the body to injury by toxins or foods the human body was never designed to process,a condition occurs called chronic inflammation. Chronic inflammation is just as harmful as acute inflammation is beneficial.
What thoughtful person would willfully expose himself repeatedly to foods or other substances that are known to cause injury to the body? Well,smokers perhaps, but at least they made that choice willfully.
The rest of us have simply followed the recommended mainstream dietthat is low in fat and high in polyunsaturated fats and carbohydrates, not knowing we were causing repeated injury to our blood vessels. Thisrepeated injury creates chronic inflammation leading to heart disease, stroke, diabetes and obesity.
Let me repeat that: The injury and inflammation in our blood vessels is caused by the low fat diet recommended for years by mainstream medicine.
What are the biggest culprits of chronic inflammation? Quite simply, they are the overload of simple, highly processed carbohydrates (sugar, flourand all the products made from them) and the excess consumption of omega-6 vegetable oils like soybean, corn and sunflower that are found in many processed foods.
Take a moment to visualize rubbing a stiff brush repeatedly over soft skin until it becomes quite red and nearly bleeding. you kept this up several times a day, every day for five years. If you could tolerate this painful brushing, you would have a bleeding, swollen infected area that became worse with each repeated injury. This is a good way to visualize the inflammatory process that could be going on in your body right now.
Regardless of where the inflammatory process occurs, externally or internally, it is the same. I have peered inside thousands upon thousands of arteries. A diseased artery looks as if someone took a brush and scrubbed repeatedly against its wall. Several times a day, every day, the foods we eat create small injuries compounding into more injuries, causing the body to respond continuously and appropriately with inflammation.
While we savor the tantalizing taste of a sweet roll, our bodies respond alarmingly as if a foreign invader arrived declaring war. Foods loaded with sugars and simple carbohydrates, or processed withomega-6 oils for long shelf life have been the mainstay of the American diet for six decades. These foods have been slowly poisoning everyone.
How does eating a simple sweet roll create a cascade of inflammation to make you sick?
Imagine spilling syrup on your keyboard and you have a visual of what occurs inside the cell. When we consume simple carbohydrates such as sugar, blood sugar rises rapidly. In response, your pancreas secretes insulin whose primary purpose is to drive sugar into each cell where it is stored for energy. If the cell is full and does not need glucose, it is rejected to avoid extra sugar gumming up the works.
When your full cells reject the extra glucose, blood sugar rises producing more insulin and the glucose converts to stored fat.
What does all this have to do with inflammation? Blood sugar is controlled in a very narrow range. Extra sugar molecules attach to a variety of proteins that in turn injure the blood vessel wall. This repeated injury to the blood vessel wall sets off inflammation. When you spike your blood sugar level several times a day, every day, it is exactly like taking sandpaper to the inside of your delicate blood vessels.
While you may not be able to see it, rest assured it is there. I saw it in over 5,000 surgical patients spanning 25 years who all shared one common denominator — inflammation in their arteries.
Let’s get back to the sweet roll. That innocent looking goody not only contains sugars, it is baked in one of many omega-6 oils such as soybean. Chips and fries are soaked in soybean oil; processed foods are manufactured with omega-6 oils for longer shelf life. While omega-6’s are essential -they are part of every cell membrane controlling what goes in and out of the cell – they must be in the correct balance with omega-3’s.
If the balance shifts by consuming excessive omega-6, the cell membrane produces chemicals called cytokines that directly cause inflammation.
Today’s mainstream American diet has produced an extreme imbalance of these two fats. The ratio of imbalance ranges from 15:1 to as high as 30:1 in favor of omega-6. That’s a tremendous amount of cytokines causing inflammation. In today’s food environment, a 3:1 ratio would be optimal and healthy.
To make matters worse, the excess weight you are carrying from eating these foods creates overloaded fat cells that pour out large quantities of pro-inflammatory chemicals that add to the injury caused by having high blood sugar. The process that began with a sweet roll turns into a vicious cycle over time that creates heart disease, high blood pressure, diabetesand finally, Alzheimer’s disease, as the inflammatory process continues unabated.
There is no escaping the fact that the more we consume prepared and processed foods, the more we trip the inflammation switch little by little each day. The human body cannot process, nor was it designed to consume, foods packed with sugars and soaked in omega-6 oils.
There is but one answer to quieting inflammation, and that is returning to foods closer to their natural state. To build muscle, eat more protein. Choose carbohydrates that are very complex such as colorful fruits and vegetables. Cut down on or eliminate inflammation- causing omega-6 fats like corn and soybean oil and the processed foods that are made from them.
One tablespoon of corn oil contains 7,280 mg of omega-6; soybean contains 6,940 mg. Instead, use olive oil or butter from grass-fed beef.
Animal fats contain less than 20% omega-6 and are much less likely to cause inflammation than the supposedly healthy oils labelled polyunsaturated. Forget the “science” that has been drummed into your head for decades. The science that saturated fat alone causes heart disease is non-existent. The science that saturated fat raises blood cholesterol is also very weak. Since we now know that cholesterol is not the cause of heart disease, the concern about saturated fat is even more absurd today.
The cholesterol theory led to the no-fat, low-fat recommendations that in turn created the very foods now causing an epidemic of inflammation. Mainstream medicine made a terrible mistake when it advised people to avoid saturated fat in favor of foods high in omega-6 fats. We now have an epidemic of arterial inflammation leading to heart disease and other silent killers.
What you can do is choose whole foods your grandmother served and not those your mom turned to as grocery store aisles filled with manufactured foods. By eliminating inflammatory foods and adding essential nutrients from fresh unprocessed food, you will reverse years of damage in your arteries and throughout your body from consuming the typical American diet.
The Joke Defense of Statin Side Effects Begin
Waiting for my reply to be posted:
Are you kidding me? First the AHA and the FDA decide that everybody should be on a statin (according to the new calculations), and now it's not the statins fault for the known side effects it has. Pretty soon, statins will replace santa claus and everybody will rejoice at hearing it's name. Check out epadruginitiative.com for more info on a safe (placebo safe) drug called Vascepa. Due to big pharma influence, the FDA has decided it doesn't want it prescribed even though it significantly lowered triglycerides, atherogenic (inflammation) markers, and LDL cholesterol. It's main competitior Lovaza, is known to raide LDL cholesterol and has major side effects. Check it out. Statin Claus, you've got to be kidding me!!
nofanofthis,
If you depend on others to create positives in your own life and believe you have no effect so be it. I on the other hand believe that giving everything I have to create those positives is the only way to go. Fail or not, I can always look at my children and be proud that I taught them to be active in life and that you can make a difference. You go on believing what you want, but don't you dare question my understanding of things. You can continue to sit on the bench believing you can not change the game. Me on the other hand, "Put me in coach, I'm ready to play".
Still need a conclusion but looking to get a petition connected to this and submit to Congress....Let me know what you think.
FDA's Possible Unethical Treatment of Amarin Corp
The FDA has a well documented history of unethical behavior and conflicts of interest. In July of 2012, Senator Grassley wrote the FDA questioning the agencies behaviors towards it's own employess who had contacted Congress about unethical behaviors within the FDA. In this letter, Senator Grassley stated, "FDA's misconduct cannot be ignored." Unfortunately we find ourselves questioning the FDA's conduct again. The facts to be presented show clear and concerning misconduct and unethical behavior by the FDA towards Amarin Corp and it's drug Vascepa. The decisions the FDA have made, or refused to make, have become alarmingly inconsistent. Congress enacted SPA provision and the FDA Modernization Act of 1997 to eliminate what was known as the moving target syndrome or repeated changes in FDA’s advice about studies needed to obtain FDA approval. Congress needs to open an investigation to sustain public confidence in, and to reinforce an open and transparent decision making process by the FDA, free of unethical behavior and conflicts of interest.
If you are not aware, Amarin Corp. is studying the effects of EPA on lipid profiles and has an approved drug called Vascepa. Vascepa significantly reduced the TG levels and improved other lipid parameters without significantly increasing the LDL cholesterol levels. Heart attacks, strokes and other cardiovascular events represent the leading cause of death and disability among men and women in western societies. According to the American Heart Association's 2010 At-A-Glance Report, over 831,000 deaths in the United States were caused by heart disease and stroke, substantially more than the approximately 572,000 reported deaths caused by cancer. (American Cancer Society. Cancer Facts & Figures 2011. Atlanta: American Cancer Society, 2011)
FACTS
1.The FDA failed to honor an SPA (Special Protocal Assessment) agreement and later reneged on this agreement to justify it's position.
The FDA approved Vascepa, as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (TG greater than or equal to 500mg/dL) hypertriglyceridemia (very high triglycerides), in July of 2011. In February of this year, Amarin submitted an sNDA (Supplemental New Drug Application), seeking approval for the marketing and sale of Vascepa (icosapent ethyl) capsules for use as an adjunct to diet in the treatment of adult patients with high triglycerides (TG =200 mg/dL and < 500 mg/dL) with mixed dyslipidemia. As part of the agreement with the FDA, Amarin was required to conduct a 12 week efficacy study (Anchor) and substantially enroll a cardiovascular study. Amarin met all obligations set by the SPA agreement with the FDA. On October 16th, the FDA held an AdCom meeting to discuss the efficacy of Vascepa. At this AdCom, the FDA explicitly questioned the efficacy of whether reducing triglycerides in the Anchor Indication would have a positive effect on coronary heart disease or its risk equivalent. Keep in mind that Amarin and the FDA, as part of the Anchor sNDA approval, entered into a SPA (Special Protocol Assessment) agreement for the design of a cardiovascular outcomes study of Vascepa formally titled REDUCE-IT (Reduction of Cardiovascular Events with EPA - Intervention Trial) to answer that exact question. The FDA, with these agreements, led Amarin to believe that once REDUCE-IT was substantially underway, the Company would have met all of the requirements to request approval of Vascepa for treating the mixed dyslipidemia patient population studied in the ANCHOR trial.
Shortly after the AdCom, the FDA rescinded the Anchor SPA, as it had determined that a substantial scientific issue essential to determining the effectiveness of Vascepa in the studied population was identified after testing began. The FDA questioned the efficacy of Vascepa, citing the outcomes results of three studies, (Accord-Lipid, Aim-High and HPS2-Thrive), which according to the FDA failed to support the hypothesis that a triglyceride-lowering drug significantly reduces the risk for cardiovascular events among statin-treated patients with mixed dyslipidemia and residually high serum triglyceride levels (200-499 mg/dL). Because the results of all three of these studies were available to the FDA when Amarin agreed to amend the SPA for the REDUCE-IT study and because these concerns were not raised to Amarin in connection with the FDAs acceptance for review of the sNDA for ANCHOR or at anytime prior to the October 16 AdCom, the FDA failed to timely notify Amarin of these new issues. According to the FDA, "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 (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". There was no mention of this change at any point leading up to the AdCom including the sNDA acceptance letter (Day 74 Letter) for ANCHOR or at any time prior to the AdCom, even though the majority of this outcomes data was available for some time.
2. The studies used by the FDA do not provide substantially new scientific information
The Three studies used by the FDA to question the efficacy of Vascepa were not an apples to apples comparison and should not be used to invalidate the efficacy of Vascepa. The three studies (Accord-Lipid, Aim-High and HPS2-Thrive), did not use the same class of drugs, nor did they involve the patient population Amarin seeks to treat. All three studies, according to the FDA, failed to prove a significant reduction in cardiovascular events. However, all three studies involved patients with triglyceride levels far below that which Vascepa is intended for. None of those outcome studies prospectively enrolled patients who had elevated triglycerides in spite of statin control with LDL cholesterol. In ACCORD, which was a Fenofibrate study, the mean triglyceride level in the overall study was just 162 mg/dL. In the Aim-High, which was a Niacin study, the median triglycerides levels were 161 mg/dL. In HPS2-Thrive, another niacin study, the mean triglycerides were 1.43(0.84) mmol/L. Not one of these studies investigated reduction of triglyceride levels in the 200-500 mg/dL range which Amarin sought approval for. ACCORD and AIM-HIGH proved nothing other than triglyceride lowering has a neutral outcome effect on people with normal baseline triglyceride levels. With respect to the population studies in the ANCHOR trial, the FDA also appears to have entered into an SPA with another company for their drug after the ACCORD and AIM-HIGH data were publicly presented suggesting that these study results were not viewed by the FDA as substantially new scientific information at that time.
3. The FDA approves Antara (fenofibrate) for the treatment of high cholesterol, mixed dyslipidemian and high triglycerides and allows fenofibrates to continue this treatment despite failed outcomes studies
On October 22nd, the FDA informed drug maker Lupin Limited (Lupin) that it had received final approval for it's fenofibrate drug Antara to treat patients with high cholesterol, mixed dyslipidemia and high triglycerides. The FDA, six days prior, used the failure of a fenofibrate study (Accord-Lipid) to question the efficacy of Vascepa and used this science to rescind the Anchor SPA agreement. The Accord-Lipid study failed to produce a significant reduction in cardiovascular events, yet Antara was approved to treat this patient population. Just recently the FDA and an AdCom panel voted to continue allowing fenofibrates to be prescribed for this patient population despite the failed outcomes trials. Again, no failed studies exist for Vascepa's efficacy in this patient population.
4. The FDA fails to allow Anchor study information on Marine Label
The FDA has failed to allow Amarin to have the ANCHOR data included in the clinical study section of the Vascepa package insert, yet, not become a formal indication for Vascepa. In doing so, the FDA may force Amarain to seek judicial relief to support their efforts, such as the right to use the ANCHOR data in commercial materials based on pre-commercial speech principles by doing the First Amendment, that protect the ability to communicate truthful information such as clinical trials results. As a comparison, the FDA affords Vascepa competitor Lovaza (GlaxoSmithKline) this exact right, which includes information for add-on therapy of Lovaza with a statin. Keep in mind the FDA rejected this study of co-administration of Lovaza with a statin as Lovaza raised LDL cholesterol. The failure of the FDA to allow Amarin to include the Anchor Indication information which is also a co-administrative treatment with a statin has been detrimental to the sales of Vascepa as sales representatives are prohibited in providing the information.
5. The FDA fails to provide Vascepa with an exclusivity designation
Exclusivity designations are made to protect drug makers from generic competition reductions and to create financial incentive for research and development. In 1992, under the Prescription Drug User Act (PDUFA), FDA agreed to specific goals for improving the drug review time and created a two-tiered system of review times – Standard Review and Priority Review. A Priority Review designation means FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review). Vascepa was approved July 26, 2012. Under any timeframe, the FDA has failed to make a ruling to the detriment of Amarin Corp. Additionally, the USPTO requested clarification from the FDA on whether Icosapent Ethyl (Vascepa) had ever been approved prior to July 26, 2013. The FDA failed to respond to the USPTO. Part of the reason for the delay in exclusivity designation was due to a Citizens Petition (known as Lovaza Citizens Petition) filed by John Fuson of Crowell and Moring LLP on February 6, 2013. Mr Fuson, who joined Crowell and Moring LLP May 30, 2012, happened to serve as associate chief counsel at the U.S. Food and Drug Administration (FDA) since 2007, where he worked with the U.S. Department of Justice's Consumer Protection Branch, bringing enforcement actions on behalf of the FDA. The petition was submitted to essentially list Vascepa's active ingredient retroactively for Lovaza, thus preventing NCE for Amarin's Vascepa. Section 505(q)(1)(F) governs the timeframe for final Agency action on a petition. Under this provision, FDA shall take final Agency action on a petition not later than 180 days after the date on which the petition is submitted. The 180-day period is not to be extended for any reason, including any determination made under section 505(q)(1)(A) regarding delay of approval of an application, the submission of comments or supplemental information, or the consent of the petitioner. To date almost 300 days later, a decision has still not been made by the FDA.
6. Sham Citizen Petitions and the anticompetitive effect
In a 95-page decision from the U.S. District Court for the Eastern District of Pennsylvania in In re Wellbutrin XL Antitrust Litigation, the court once again addressed the issues of “sham” citizen petitions, liability under the Sherman Antitrust Act, and Noerr-Pennington immunity. The court previously addressed citizen petitions alleged to be shams in In re Flonase Antitrust Litigation, 795 F. Supp. 2d 300 (E.D. Pa. 2011). When petitioning activity “ostensibly directed toward influencing governmental action[] is a . . . sham to cover what is . . . nothing more than an attempt to interfere directly with the business relationships of a competitor[, then] the application of the Sherman Act would be justified.” Noerr, 365 U.S. at 144. The sham exception requires that a petition be “(i) ‘objectively baseless,’ and (ii) ‘an attempt to interfere directly with the business relationships of a competitor through the use of the governmental process – as opposed to the outcome of that process – as an anticompetitive weapon.’” Primetime 24 Joint Venture v. Nat’l Broad. Co., 219 F.3d 92, 100-01 (quoting Prof’l Real Estate Investors, Inc. v. Columbia Pictures Indus., Inc., 508 U.S. 49, 60 (1993) (“PRE”)). The Lovaza Citizens petition, filed by Crowell & Moring asks "... the Commissioner could adopt a strength for Lovaza based upon the fixed amount of major omega-3-acid ethyl esters specified in the Lovaza reviews and labeling. According to its currently-approved labeling, "at least 900 mg of the ethyl esters of omega-3 fatty acids sourced from fish oils" "are predominantly a combination of ethyl esters of eicosapentaenoic acid (EPA - approximately 465 mg) and docosahexaenoic acid (DHA - approximately 375 mg)." By requesting EPA to be listed retroactively, the petition has created uncertainty and delay in the FDA's exclusivity designation of Vascepa. Lovaza maker GSK has opposed each and every request and recommendations made in the petition. GSK refutes the citizens petition by stating that the entire fish-oil based mixture in Lovaza-not just the ethyl esters of omega-3 fatty acids-constitutes the active ingredients. Because this petition interfered directly with the business relationship of a competitor, it needs to be investigated and determined with whom Crowell and Moring are representing.
labner,
Thank you.
Biochica,
I am working on a letter and I believe it was you who mentioned the difference in label allowance between Lovaza and Vascepa. Can you provide me a synopsis on the difference or point me to articles that explain the difference?
Larry Husten was the Forbes contributor I quoted.
Just so we are clear, I do not think amarin is going bankrupt anytime soon. I was quoting the author of the forbes article which states that if amarin cancelled the study, the cholesterol experts believed the NHLBI should pick up the study. I don't think Amarin will cancel the study, therefore if the NHLBI did pick up the study, Amarin would cease to exist. All Hypothetical based on the Forbes article.
Biochica,
I have emailed the company and the NIH in regards to this exact issue. Citing members of the AdCom panel, I explained how scientists felt the completion of Reduce-It is very important. We'll see what happens. Others should do the same!
ep,
The following quote was taken from Forbes columnist Larry Husten the day the SPA agreement was rescinded.... "But if Amarin does abandon the trial, is there an alternative? Some cholesterol experts I’ve spoken with believe the NHLBI should pick up the trial if it is abandoned"
I find it strange that some cholesterol experts were already talking about saving this study the day the SPA was rescinded, yet the effects of Vascepa were downplayed by the FDA at the AdCom. Just seems strange to me.
Comparative Effectiveness of Fish Oil Versus Fenofibrate, Gemfibrozil, and Atorvastatin on Lowering Triglyceride Levels Among HIV-Infected Patients in Routine Clinical Care(November, 2013
Among HIV-infected patients with moderate hypertriglyceridemia in clinical care, fibrate therapy remained the most effective at reducing TG levels. Fish oil had a much more modest impact on TG levels, likely in part because of the frequent use of low doses in the usual care setting. However, when considering risks and benefits, fish oil may be an attractive option for HIV-infected patients with moderately elevated TG, particularly among patients who may not want or tolerate fibrates. Additional studies are needed to further determine the appropriate indications and the lipid-lowering effects of fish oil in HIV-infected patients.
Maybe Vascepa 4g would be a better treatment option?
sts66,
I'm guessing if the NHLBI took over the study, it would mean that Amarin would cease to exist. I've emailed the NHLBI asking them to support Amarin and quoted this author. If finishing this study is important for science, these govt. agencies should be supporting its finish.
Pretty interesting that a Forbes contributor, Larry Husten, has this to say the day that the SPA was rescinded, "But if Amarin does abandon the trial, is there an alternative? Some cholesterol experts I’ve spoken with believe the NHLBI should pick up the trial if it is abandoned"
Experts already talking about the government picking up Reduce-It. Must be an important study. Was this the plan all along?
By SummerStreet Research in May. Dr. Brinton who (supposedly) made these comments later retracted his statement. "I don't know why SummerStreet quoted me as saying that because they're wrong. It's annoying to be misquoted." said Dr. Eliot Brinton
SummerStreet stood by its report in a statement issued to clients Wednesday. "We stand by yesterday's comments and state our story is accurate."
It seems insiders were well aware that the AdCom was going to be negative, just look at AF's confidence regarding this. Would have been nice to be in this circle!!
There was a large primary care conference held in Washington DC last week and attended by approximately 800 primary care providers (doctors and nurse practitioners). The conference is held in a different city almost every week and thus an has audience of tens of thousands of primary care providers every year. During the three day conference there were two lecturers on fish oils. At one lecture, conducted by a member of Amarin's steering committee for its outcome study, said that triglyceride levels above 500 should be treated because they lead to pancreatitis. He said however fish oil is one of many treatments that can lower triglycerides. He also said until the outcome trial is complete there is no reason to give Vascepa to patients with triglyceride levels below 500. Based on this public comment from an Amarin insider, we reiterate our opinion that the FDA will not approve Amarin's Vascepa for triglycerides below 500 until the outcome study is complete. If by chance it does get approved without outcome data we believe sales will be disappointing.
Are you as sure about this as you were about John Fuson's connection to the citizens petition???
sts66,
You are completely wrong..... Last page of Lovaza CP signed by none other than Mr. John Fuson
Division of Dockets Management
February 6, 2013
Page 7
C. ENVIRONMENTAL IMPACT
An environmental assessment report on the action requested in this Petition is not
required, as Petition claims a categorical exclusion under 21 C.F.R. § 25.31(a).
D. ECONOMIC IMPACT
A statement of the economic impact of the requested action will be provided if required
by the Commissioner following review of this Petition, in accordance with 21 C.F.R. § 10.30
E. CERTIFICATION
The undersigned certifies that, to the best knowledge and belief of the undersigned, this
Citizen's Petition includes all information and views on which the Petition relies, and that it
includes representative data and information known to the Petitioner that are unfavorable to the
Petition.
Respectfully submitted,
John H. Fuson
Crowell & Moring LLP
1001 Pennsylvania Ave. NW
You wanna see scripts start skyrocketing....
Allow the Anchor data and the ability of sales reps to communicate this information to Doctors who currently prescribe Lovaza for mixed dislypidemia. Better drug wins! This in itself may be enough to propel the company to the finish line of Reduce-It.
1,200 Signatures!!
Keep pushing. The awareness alone will drive scripts!
Who are you to mock BB for anything he does? The rest of us on here have done a ton of research on this stock, yet here we sit as bagholders. As for BB mentioning Reduce-it alternatepatel, maybe you should put that statement into context. He said anything could be applied, Vascepa bad for your health up to Reduce-It.
BB, I appreciate all your hard work. Right or wrong, agree or disagree, I am thankful!
I think the volume after hours Wednesday and today clearly show that no deal has been made. If there was a deal, somebody in the know would have been buying up big time.
Most have been wrong on this stock, but IMO none of us are wrong on the science. Whether or not it takes until Reduce-It is completed, the TRUTH will be known. The company just needs to survive until then. Happy Thanksgiving all!!
Great Find!!
BB,
This paragraph tells me nothing has changed.
Also within 14 days, amend all pending supplemental applications that includes labeling changes for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this supplemental application
My thoughts are.....who cares! It's thanksgiving and I want to enjoy my days off and not think about this joke of a company.
said as he/she types away on a stock site message board.
Very ironic to say the least!