Amarin Corp Plc (AMRN)

[Biobillionair]

Guy,

The evidence you produced is old news and currently outdated. MAPP 5021.1 was effective immediatly when published in March.

I encourage you read the whole policy, but to save you time specifically page 3 "C. CDER Application of Exceptions".

"b. Scientific evidence demonstrates the salt form affects the absorption, distribution, metabolism, and/or excretion (ADME) of the drug in a manner that influences the clinician’s product selection"
http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/UCM340273.pdf

The Plasma EPA levels after 4 grams of Lovaza are about 60 mcg/ml (about because they give the range of all 20 subjects dosed). The Plasma levels after 4 grams of Icosapent Ethyl or Vascepa are 347 mcg/ml or 578% higher than the max dose of Lovaza approved by the FDA. I would say that's "exceptional", and would be deserving of an exception. These are facts that can't be argued, they are printed FDA documents. Most new after the approval of Vascepa 2012. Your old documents mean nothing to the decisions to be made regarding Vascepa's NCE status.

This happens to be the whole design of a prodrug, it provides vastly superior delivery of active moiety to the target.

Lovaza's active moiety was ill defined. The FDA has clearly defined it as a mix of ethyl esters (excluded from MAPP 5021.1 policy) extracted from fish.
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM320011.pdf

Vascepa's active moiety is Icosapent Ethyl, very well defined and described as a prodrug in it's FDA approval documents. It is derived from fish oil.
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM347002.pdf

The two have separate draft Guidances for a reason, they are consider two different active moieties...period. Not my opinion but fact at the FDA.

Circular arguments can be made on this all day. I believe I'm correct.

The FDA considers Icosapent Ethyl a prodrug of EPA. The active moiety is Icosapent Ethyl that acts as a type 2 prodrug activated by pancreatic lipase. A 4 gram dose of Icosapent Ethyl achieves 575% greater plasma EPA levels when comparing to a max dose of Lovaza. This is exceptional and falls under the exception in MAPP 5021.1. This is my opinion after reading all these documents, your free to bet against me.

Williams