Replies to post #60514 on Biotech Values

[DewDiligence]

Re: RDEA, IDIX and NNRTI’s for HIV

>In the CC yesterday, Ardea said that in the phase IIa, plasma lipid levels (particularly triglycerides) stabilized or decreased over the course of treatment with RDEA806. A similar trend was observed in the phase I studies… (I think that Sustiva has the opposite trend).<

Sustiva did raise total cholesterol in the HIV cocktails that formed the basis for FDA approval in 1998, but these cocktails are now rarely used in the U.S., where the overwhelming majority of Sustiva use is in more modern cocktails and as a component of Atripla. Moreover, the assertion on RDEA’s webcast about Sustiva’s adverse effect on triglycerides does not seem to be supported by the FDA label (from page 34):

http://www.fda.gov/cder/foi/label/2007/020972s029,021360s016lbl.pdf

>>
Lipids: Increases from baseline in total cholesterol of 10-20% have been observed in some uninfected volunteers receiving SUSTIVA. In patients treated with SUSTIVA + zidovudine + lamivudine, increases from baseline in non-fasting total cholesterol and of approximately 20% and 25%, respectively, were observed. In patients treated with SUSTIVA + indinavir, increases from baseline in non-fasting cholesterol and HDL of approximately 40% and 35%, respectively, were observed. Non-fasting total cholesterol levels >=240 mg/dL and >=300 mg/dL were reported in 34% and 9%, respectively, of patients treated with SUSTIVA + zidovudine + lamivudine; 54% and 20%, respectively, of patients treated with SUSTIVA + indinavir; and 28% and 4%, respectively, of patients treated with indinavir + zidovudine + lamivudine. The effects of SUSTIVA on triglycerides and LDL were not well characterized since samples were taken from non-fasting patients. The clinical significance of these findings is unknown.
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>And how do other NNRTIs (IDX899) behave [on lipids]<

Good question; I do not know the answer, but I will try to find out. Regards, Dew

[DewDiligence]

Addendum re RDEA, IDIX and NNRTI’s for HIV:

What may be more consequential than the lipid profiles of the various NNRTI drugs for HIV are the sizes of the pills. As touted on RDEA’s webcast, the ability to formulate RDEA806 into a tablet where only 20% of the volume consists of excipient is important in pursuing a 3-in-1 Atripla-like pill that includes RDEA806 as the NNRTI component.

IDIX realizes this too, and it’s the main impetus for testing lower doses of IDX899 than the ones tested to date. (This was the subject of a recent quiz on this board.)