Amarin Corp Plc (AMRN)

[Biobillionair]

History of 80% interim:
April 2016 e-mail to Amarin and Woodcock

Janet,

As you are well aware, Amarin gave up the SPA appeal in the fall of 2014 and then in the Spring of 2015 you answered the EPADI CP and delivered a CRL to Amarin for the Vascepa sNDA 005. These regulatory actions directly led to Amarin’s recent First Amendment settlement with the FDA. Beyond the expense of litigation to both FDA and Amarin these regulatory decisions have circumvented AACE/ACE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM 2016 preventing patients from affordable, efficient access to the recommended treatments. These guidelines contained the same treatment recommendation in 2013 when the FDA rescinded Anchor SPA. Amarin has stated in an SEC filed document, “The FDA has acknowledged that the standard of proof required by the FDA for approval of a new drug indication is higher than that generally used to inform patient treatment guidelines and that used by physicians in clinical practice”, yet you have admitted to me in a prior communication the FDA does not practice Medicine. Your assertion the FDA doesn’t practice medicine is not convincing, Amarin’s above statement, in a legal document, doesn’t correlate with FDA usurping 2013 AACE treatment recommendations to treat triglycerides 150-500 mg/dL in the “Anchor” population. Instead the Anchor SPA rescindment was upheld through the level of Dr. Jenkins and a Policy Committee which involved you. In my opinion this is a serious medical ethical breach by the FDA. Medical ethics is based on four principles: 1) Respect for autonomy-the patient has the right to refuse or choose their treatment 2) Beneficence-a practitioner should act in the best interest of the patient 3) Non-maleficence-“first, do no harm” (primum non nocere) 4) Justice-concerns the distribution of scarce health resources, and the decision of who gets what treatment. The Anchor SPA rescindment fails ALL 4 basic principles. Patients don’t get the right to chose when the drug is off-label, not covered and requires CMS prior authorization. The FDA has clearly not acted in the best interests of Type II diabetics that are two times more likely to die of a cardiovascular related event. Vascepa has been proven to have a placebo like side effect profile, thus doing no harm. Finally, the outcome of RI is likely to prove the FDA’s intentional blockade of this at need treatment population wasted scarce US health care resources.


For these reasons I have requested (demanded) Amarin complete all further levels of Anchor SPA appeals. They have the option of refusing my request but from an ethical standpoint I think my request is more than reasonable.


You also have the Regulatory option to reconsider EPADI Citizen Petition, I would suggest you take the ethical high road and do this immediately.


Had the FDA taken my recommendations early on, none of this mess would have occurred. I have included Amarin Investor Relations in this communication to hopefully facilitate a timely ethical decision by both parties.




Thank You for Your Consideration,



Jason R Williams



Hi Kate,

I can’t help but feel Amarin isn’t properly communicating all the relevant facts behind the conversations that led Amarin to include this statement in it’s last 10-K: pages 3-4 investor.amarincorp.com/secfiling.cfm?filingID=1193125-16-476872&CIK=897448

"In April 2015, we received a Complete Response Letter, or CRL, from the FDA in response to our supplemental new drug application, or sNDA, that sought approval of Vascepa for use in patients with mixed dyslipidemia, based on the successful ANCHOR study. The CRL followed an October 2013 rescission by the FDA of a special protocol assessment, or SPA, agreement and three failed attempts by us to appeal that rescission at FDA. The FDA has acknowledged the success of the ANCHOR study, which met all primary and secondary endpoints. However, FDA determined that there were insufficient data to conclude that drug-induced changes in serum triglycerides could be recognized by the FDA as a valid surrogate for reducing cardiovascular risk in the ANCHOR population for the purpose of regulatory approval of a drug targeted at a triglyceride-lowering indication in this population. The FDA has acknowledged that the standard of proof required by the FDA for approval of a new drug indication is higher than that generally used to inform patient treatment guidelines and that used by physicians in clinical practice. The FDA did not determine that the drug-induced effects of Vascepa, which go beyond triglyceride-lowering, would not actually reduce cardiovascular risk in this population and the FDA has encouraged us to complete the REDUCE-IT outcomes study. Based on our communications with the FDA, we expect that final positive results from the REDUCE-IT outcomes study will be required for label expansion for Vascepa."

The FDA can’t raise the standard of proof higher then professional treatment guidelines without making a unilateral decision for CMS to ignore the medical needs of this patient population. Amarin has an ethical duty to do everything in it’s regulatory arsenal to march this decision to the top of HHS administration.

Amarin’s business is based off collecting reimbursement from private and Government funds to treat the above population, by winning the “First” suit Amarin is the first Bio Pharma to be place in the unique position of being part of the Health Care team. You don’t want Amarin to be the weak link in the Anchor chain, from a medical ethical standard Dr. Califf must defer to the professional guidelines.

In my opinion, Amarin takes a great clinical risk by not finishing the full SPA appeal, litigation is only an option if the last level refuses to reinstate SPA. Using the cost of this potential litigation to excuse the virtually free remaining three levels is an excuse I can not accept. Amarin’s “First” settlement terms have redefined Amarin’s role ethically, you better make a stand to protect your patients. I also understand Amarin has been accused by the FDA of collaborating with stakeholders, Amarin needs to simply point out the fact the FDA has forced this relationship due to it’s regulatory actions of SPA rescindment. When patient safety is in question, clinicians don’t wait weeks to pontificate a decision. Please share this with whomever. I have no choice but to wait for Amarin’s decision I have made my opinion known to both Congress, FDA and Amarin. When Amarin has reached a decision on how to deal with my request please contact me, I think Congress needs to update legislation to clearly state the FDA can’t usurp professional guidance.

My conference call with Amarin 4-26-2016 11am

Requested Amarin finish ANCHOR SPA appeal, JT disagreed, we agreed to disagree. I informed him I would forward my communication with FDA to him.

It took weeks of arguing with FDA to "allow" me to file a formal dispute resolution request, here's one of many communications with CDER Ombuds:

Virginia,
I’m moving forward with the Formal Dispute Resolution procedure. I request the appeal starts above Dr. Janet Woodcock to her direct supervisor for the following reasons. On March 27th, 2015 Dr. Janet Woodcock, Director Center for Drug Evaluation and Research denied Citizen Petition Docket No. FDA-2013-P-1612. She states, “the decision to dispute an FDA action with respect to a SPA agreement made by the sponsor that entered into the SPA agreement with FDA. Therefore, your request to overturn a decision by an FDA review division regarding a SPA agreement is denied.” This response is inconsistent with FDA regulations (21 CFR 10.75), which provides a mechanism for any interested person [An interested person is a person who submits a petition, comment or objection or otherwise asks to participate in an informal or formal administrative proceeding or court action (21 CFR 10.3)] to obtain formal review of ANY agency decision by raising the matter with the supervisor of the employee who made the decision.

I personally commented and requested that the FDA “overturn the FDA’s decision to rescind the Special Protocol Assessment [SPA] Agreement for the ANCHOR trial” and “investigate the reviewing division for possible misconduct during the ANCHOR sNDA review process including concern with the timely communication and conveying of key issues to the sponsor”. The review division did not follow the guidance for the industry prepared by the Review Management Working Group in CDER, following the appropriate communications prior to convening an Ad Com to discuss the rescindment of a SPA.
Specifically Amarin receive no prior communication the agenda posted to the public registry had been changed to an Advisory Committee & vote used to rescind ANCHOR SPA.

Both the Formal Dispute Resolution: Appeals Above the Division Level, Guidance for Industry Special Protocol Assessment, and Dr. Woodcock’s denial to the Citizen Petition I comment on, provides me the the status to participate in this formal administrative proceeding.

Please provide me with the next steps.

Thank You,

Jason R Williams

May 17th 2016 First FDRR sent to Khushboo Sharma

Ms. Sharma:

Pursuant to 21 CFR 10.75 Internal agency review of decisions, specifically under “(c) An interested person outside the agency may request internal agency review of a decision through the established agency channels of supervision or review.” I have followed the Agency’s Final Guidance (OMB Control No: 0910-0430) with the submission of this Formal Dispute Resolution Request (FDRR). I’ve included 6 primary exhibits that are part of the record on file and no new information is presented. (exhibits will follow in second e-mail)

Also pursuant to 21 CFR 10.75 I request this matter be expeditiously reviewed by the Office of the Commissioner based on “Personal review of these matters by center directors or the office of the Commissioner” specifically (3) In unusual situations requiring an immediate review in the public interest. The detailed actions below have directly delayed a safe effective treatment to a large Diabetic Cardiovascular Population. The clinical risk benefit is such, that the treatment is contained in clinical guidelines for practicing Endocrinologist. This delay is contrary to the FDA’s stated mission. I personally believe the public is at risk.

Sincerely,

Jason R Williams

In the FDRR under "Possible Solution" #3 I proposed:

That DMEP consider a type A meeting, after SPA is reinstated, to request for Amarin and the Agency to negotiate a REDUCE-IT SPA amendment with a procedure to retract the "ANCHOR" label approval if the results of REDUCE-IT CVE trial do not pass the defined outcomes of the REDUCE-IT SPA. This procedure should strictly follow the SPA Protochol Assessment Guidance.

August 2016 Amarin and FDA announced 80% interim

I expect label change with 80% announcement. This has all been public knowledge and posted to IHUB

BB