To the Senate HELP committee members.
Honorable Madams and Sirs:
I beseech you to consider a serious breach of conduct and contract by the FDA. The matter involves the FDA's shameful treatment of Amarin Corp. regarding its drug Vascepa. Vascepa is a highly purified ester of eicosapentaenoic acid (EPA), a principal omega 3 found in fish oil. Current scientific research overwhelmingly supports the notion that pure EPA in adequate dosage will cut the risks of heart disease and strokes. The evidence is bolstered by population studies in the Japanese and Inuit, which show a clear and convincing relationship between the amount of EPA in the diet and the risk of coronary heart disease.
Around 2009, the FDA and Amarin entered into a Special Protocol Assessment agreement (SPA). An SPA is a congressional creature designed to prevent the FDA from changing the goal posts in terms of what information or tasks a sponsor company must accomplished to get market approval by the FDA; this was a huge problem for biotechs prior to this congressional action.
The SPA is a written, binding instrument to which both parties agree and which cannot be changed except by mutual agreement. The only exception was the absolutely necessary proviso that the FDA could rescind the SPA if new evidence (i.e. after the commencement of the trials) indicated there were heretofore unknown safety issues, or information that the drug would not be effective. Obviously, if a legitimate concern regarding either of these issues emerged, there would be little reason for either the FDA or the company to wish to proceed. The agreed upon terms in the Vascepa SPA was that the sponsor would run a short clinical trial, ANCHOR, determining the safety and efficacy of the drug. After FDA approval of ANCHOR, then the company would have to design and implement an FDA- approved larger clinical outcomes trial (REDUCE-IT) where Vascepa would be an "add on" drug combined with patients taking statins. The FDA's requirement was that the company meets a 50% enrollment (4000 patients) in REDUCE-IT to complete the FDA's requirements.
In the spring of 2013 the FDA notified the company the conditions of the SPA had been met and that the company could now submit an application for marketing (sNDA) for the very large mixed dyslipidemia indication.
The company filed for the sNDA, and the FDA accepted the paperwork without comment and things appeared to be going smoothly. In the summer of 2013 the FDA notified the company it was scheduling an Advisory Committee (Adcom) meeting in October to consider Vascepa. This appeared routine as Vascepa would be the only FDA-approved drug for the dyslipidemia group. An Adcom meeting is one in which the FDA brings in people who are not full time FDA employees, but are on call to the FDA for such meetings. These people are physicians, epidemiologists, consumer advocates, statisticians, etc. They form a voting panel. On the Vascepa panel no more than two of the panelists had more than a layman's knowledge of the physiology of EPA, the principal ingredient of Vascepa.
The FDA then revealed they were skeptical of the fact that Vascepa would lower coronary risk because they considered only the triglyceride lowering effect of EPA. They based this skepticism on three drug trials testing the effect of trig lowering on cardiac risk. The three trials did not use EPA, but instead used either niacin or fibrates. These are active ingredients which bear absolutely no similarity to EPA and have vastly different physiological effects.
Not only did the FDA use drugs which bore little similarity to EPA, the FDA failed to notice in the three triglyceride (TG)-lowering trials the majority of patients did not have high TGs, but were in the low to borderline TG range. This error on the part of the FDA led to the incorrect conclusion that triglyceride-lowering treatment in patients with high TG levels would not be beneficial. The reality is niacin and fibrates did lower TGs, but this lowering occurred in normal range where patients were not considered at risk. The FDA conclusion was wrong, and cannot be derived from outcome trials having normal TG patients. Thus, the FDA reason for rescinding the SPA had absolutely no scientific merit.
This was subsequently pointed out to the FDA, which then countered the statement. They said that they were changing their opinion on the predictive value of blood surrogate markers such as triglycerides and concentrating only on low density lipoprotein cholesterol (LDL-C) following the lead of the AHA which is heavily subsidized by the statin manufacturers. Many other health experts disagree that TGs are not risk factors, including the American Diabetic Association, American College of Endocrinology, and the National Institute of Health.
Some days later the FDA informed the company it was rescinding the SPA based on its "new science.”
The FDA also ignored the only large scale outcomes trial based on EPA as a statin add on, JELIS. This is a Japanese study that showed an across the board 20% reduction in coronary risk. FDA denigrated the study because it was not double blinded and because the enrollees were Japanese.
FDA's actions in this case are exactly what congress intended to put an end to. That is the capricious, irresponsible, and penal changing of the expected requirements of a sponsor company. Furthermore the FDA has put the stall on Amarin, which is required to appeal the FDA's decision through six levels of FDA bureaucracy, each level taking months to render a predictable response. Of note, the FDA has not told or in any way suggested the company should terminate the REDUCE-IT study, nor has any of the FDA's "science” convinced the company to abandon the trial.
In the meantime, Amarin has lost millions in much need revenue to continue the trial and patients who could be benefitting from Vascepa are dying. There were no significant safety issues known before the trials began and none have emerged, so this is not a risk benefit matter.
Please, Senator, look into this. The life you save could be your own or someone you know.
Respectfully,
AI
