ENCY/MYOG
drbio45,
I've been looking into this a bit & I'm leaning toward your scepticism of the MYOG announcement. Why are the 6MWD numbers for the ARIES1 test so much better than for the phase II study? Secondly, the earlier results did not show a dose response whereas The ARIES1 trial shows a huge dose response. (both of which you alluded to)
MYOG's December announcement also doesnt indicate what % were class II vs class III patients. Their numbers for placebo-corrected 6 MWD would seem quite impressive if they included a large % of class II patients since the usual case seems to be that healthier patients show a lower relative improvement. So why didnt they present the specfics of their population? In addition, their earlier, smaller patient populations did contain several patients in the treatment arms that showed increases in serum aminotransferases greater than three times the upper limit of normal range. Makes one wonder.
The thelin trial populations tended to contain about 20% with connective tissue (CT) disease & as you pointed out these patients dont tend to respond well to treatment. The CT patients would drag thelin's absolute 6MWD numbers down but presumably the placebo population would contain a similar population so the relative numbers shouldnt suffer. I dont think that elimination of CT patients from the MYOG trials would enhance ambrisentan's placebo corrected numbers but they are comparing apples & oranges as far as patient populations are concerned. MYOG also didnt include patients with congenital heart disease whereas the Thelin trials did. Portrayal of superiority in such cases makes me sceptical.
I dont doubt that ambrisentan is an effective drug. I just have my doubts as to the robustness of the information that MYOG has recently released & that it is as effective as the market seems to think. Looks to me like ambrisentan would split market with Thelin for class II & would share market with Tracleer & Thelin for class III while Thelin & Tracleer have class IV.
Any idea how the NYHA and WHO classifications compare?
Also kind of curious as to where you got the 20:1 selectivity number for ambrisentan. Not doubting it's validity since I've seen numbers ranging from 77:1 (Motte 2005 Pharmacology & Therapeutics in press) to 260:1 (Teerlink 2004 Business Briefing:US Cardiology) so there's obviously some uncertainty. In anycase, intermediate in selectivity between Thelin (6500:1) & Tracleer (which I think is close to 20:1 but I might have that reversed). If ambrisentan does turn out to be more effective than Thelin it might indicate an optimal level for blocking the ETA receptor relative to the ETB receptor.
Charlie
BTW I'm not an MD, biologist, or statistician of any variety so please treat any errors kindly but I do appreciate commentary.
