I read the Briefing Documents, both from the FDA and those put out from Amarin. Lots of information to digest. I'm dead tired as I stayed up all night doing it (couldn't sleep anyway). It is obvious to me that the contents leaked to several parties way prior to the infamous Bloomberg article/headline. I might be missing something here but the FDA BD is pretty negative and Amarin's responses are pretty weak. The reviewer calls into question, numerous times, the results of the ANCHOR trial,based on the placebo numbers. A large portion of the BD encompasses running down previous outcome study results and crapping all over JELIS. Here is a gem from pages 81-82 under "Reviewers Comments"
Reviewer comment: Following the release of ACCORD-Lipid results in 2010, the FDA held an
advisory committee meeting to discuss the findings of the ACCORD-Lipid trial as they related to
the indication granted to fenofibric acid (Trilipix) for coadministration with a statin. Since
2008, Trilipix is FDA-approved for use in combination with a statin to reduce TG and increase
HDL-C in patients with mixed dyslipidemia and CHD or a CHD risk equivalent who are on
optimal statin therapy to achieve their LDL-C goal.
EMDAC members were asked to comment on their interpretation of the two subgroup analyses
with significant interaction terms suggesting a treatment effect according to gender and baseline
lipid subgroups (TG=204 mg/dL, HDL-C=34 mg/dL), in the context of the negative ACCORDLipid
MACE primary outcome. In response, members cautioned against the over or under
interpretation of subgroups from clinical trials in general, but particularly with negative trials.
Suggestions of benefit or harm from subgroup analyses were defined as hypothesis generating
that should not alter clinical practice or regulatory decisions until properly validated, especially
in the context of an overall null result.
Members voted unanimously to require the conduct of a clinical trial designed to test the
hypothesis that, in high-risk men and women at LDL-C goal on a statin with residually high TG and low HDL-C, add-on therapy with Trilipix versus placebo significantly lowers the risk for
MACE. Furthermore, members commented that numerical benefits in lipid surrogate endpoints
such as TG and HDL-C when added to statin therapy should not trump clinical outcome data.
Finally EMDAC made recommendations to the FDA regarding what further actions to take
regarding Trilipix’s current indication for coadministration with a statin including (a) continued
marketing with or without revision to labeling or (b) withdraw approval of Trilipix’s indication
for coadminstration with a statin. The majority of members voted to allow the indication to
stand pending the results from a dedicated CVOT. Some members felt there was not enough
evidence from the ACCORD-Lipid trial relevant to the specific Trilipix coadministration
indication to warrant withdrawal of the indication. Others felt that with no additional relevant
clinical evidence provided by ACCORD-Lipid, and because the indication had already been
granted based on numerical improvements and supported by regulatory standards of the time,
this should be honored until further information on clinical outcomes were available. However,
several members recommended that the FDA consider requiring a different level of evidence for
future lipid altering drugs, transitioning away from surrogate endpoints to relevant clinical
cardiovascular outcomes especially for indications for add-on therapy to statins.
I'm a long time "long" on AMRN but I have to say that the FDA BD was a real shit sandwich. Amarins core argument in their BD was that lowering Trigs in effect lowers Non HDL-C which IS considered an accepted risk factor for CVD. However in the ACCORD trial trigs were lowered 22.2%,LDL-C was lowered 18.9% and HDL went up 8.4%. I could go on and on and on about the reviewer shredding the basic core Amarin argument based on failed outcome studies.Amarin does a good job of dissecting previous Omega 3 studies but fails to explain (by ommision) why other outcome studies which were better at lowering trigs than Vascepa failed to show an outcome. The JELIS results were explained by the reviewer by pointing out that the baseline LDL-C levels were high because participants were not on optimized statin therapy but were on low dose statins and that LDL-C dropped when combined with EPA by 25% while trigs merely dropped by 9%.
Any of the oldtimers who wants to discuss this further, feel free to contact me at richinjun@yahoo.com. If I recognize you as a legit long I'll be glad to discuss
AI
