Amarin Corp Plc (AMRN)

[HDGabor]

Regarding the Bill:

http://thomas.loc.gov/cgi-bin/bdquery/z?d113:HR04800:@@@S

http://www.whitehouse.gov/sites/default/files/omb/legislative/sap/113/saphr4800r_20140610.pdf

House Committee on Appropriations Chairman Hal Rogers has stated that his goal is to pass all twelve regular appropriations bills for 2015 before Congress has a recess in August.

Regarding the SPA reinstatement and ANCHOR approval:
The SPA and ANCHOR approval is two ‘separate’ issue, however:
a.) if SPA will be reinstated the Division has to approve ANCHOR
b.) the Division could approve ANCHOR without SPA reinstatement

Without assumption for the outcome, the facts:
- Drugs basically approved based on hard outcome, however the FDA COULD (but not have to) approves drug based on surrogate endpoints
- With rare exception, FDA has historically considered granting approval for lipid-altering drugs based on favorable changes in the lipid profile
- no existing guideline for lipid-altering drugs (as I know: Clinical Evaluation of Lipid – Altering Agents / Clinical Medical Draft - 4/16/2010 / Withdrawn - http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079655.pdf)

- During the pre-IND meeting in 2008 FDA discussed and noted that there were ongoing cardiovascular outcomes trials -- ACCORD-Lipid, and AIM-HIGH, to name two -- that these trials would provide important information on the incremental benefit of adding second lipid-altering drug to statin therapy, BUT they did not conclude anything till the AdCom’s BD, meanwhile ACCORD-Lipid was published in 2010 and AIM-HIGH in 2011.

- According to FDA the currently available data from studies of other therapies do not support use of drug-induced reductions in serum triglycerides as a basis for approval of an indication that DMEP views as ostensibly and impliedly an indication to reduce the risk of cardiovascular disease – HOWEVER these studies were different dugs and different target population

- Although treatment effects of non-statin lipid-altering therapy have been suggested in several trials in variably defined high TG/low HDL-C subgroups, the hypothesis has not yet been tested that a patient population can be prospectively identified who will benefit from such therapy
- Two recently published study strongly support the hypothesis, provide encouraging new data connecting reduced TG levels to reduced CV risk but not confirmed it
- DMEP stated that information submitted by Amarin supports testing the hypothesis that Vascepa (icosapent ethyl) 4 grams/day versus placebo reduces major adverse cardiovascular events in statin-treated subjects with residually high triglyceride levels, as is being studied in the Vascepa REDUCE-IT cardiovascular outcomes study

- since October, 2013 FDA approved several generic drugs for niacin and fenobirates …

So:
- Did FDA breach any procedure? – No, SINCE no existing, available guideline for lipid-altering drugs and for “when substantial scientific issue essential”
- Did FDA follow the unworldliness of Congressional Record and the 1997 PDUFA Goals Letter? – No. They breached it in every respect.
- Was the hypothesis changed? - Not really. It’s still not confirmed but the citied studies did not null the hypothesis due to different target population (moreover subgroups and recent studies give more support, make it stronger)
- Was FDA ‘fair’ with Amarin? - No, since they did not notifying Amarin within a reasonable period of time after FDA becomes aware of new science.
- Will FDA generate any damage for patients if approve ANCHOR? - No, MOREOVER reduce the risk since Vascepa is safer than the approved drugs (niacin, fibrates)
- Has to FDA approve ANCHOR? - No