Biotech Values

[iwfal]

ESPR ISIS —

Respectfully disagree with Larry Huston’s contention that a failure of MRK’s IMPROVE-IT study will drastically alter regulators’ acceptance of LDL as a surrogate endpoint. IMPROVE-IT failure will have some ramifications, of course, but it won’t (IMO) preclude the approval of relatively safe small-molecule drugs such as ETC-1002, based primarily on LDL and secondarily on other biomarkers such as CRP.

I think Larry's point, with which I would agree, is that a "drastic" change isn't really needed to utterly shut down the use of surrogate lipid markers as adequate for a heart disease prevention indication. The AdCom materials and other stuff coming out from the reneging of the Amarin's SPA is pretty unambiguous that the FDA has doubts (well founded in my opinion) about lipid bio markers of all forms. Essentially there are no strong non-statin drug outcomes trials that 'show' LDL reductions (via drug) improve outcomes. And there is good reason to believe much of the benefit of statins is not LDL related.

Put another way - LDL, for reasons that seem to be primarily societal, has long been treated as if it were specially blessed as a marker. And while the current data isn't strong enough to say that isn't true, neither is there any compelling data to say that it is a good treatment marker. I.e. It lacks proof one way or the other. And in biotech I think everyone (including the FDA) recognizes that something lacking proof is not a good bet.

BTW - as a marker of people's belief that LDL is somehow special in the pantheon of cholesterol markers... A question: do you think that ISIS' ApoC3 drug should be approved for CHD? Amarin's trig lowering oil?