RE:Various questions and observations from a newbieTundup,
RVX-208 is an inhibitor of the BET (bromodomain and extra-terminal) family, and has a mechanism of action that seems to be primarily epigenetic, resulting in a broad, beneficial reprogramming of cells resulting in an elevation of apoAI/HDL, decreased inflammation and improved glucose control.
PCSK9 inhibitors target the PCSK9 protein, which is involved in degradation of the LDL receptor. Inhibiting PCSK9 leads to elevated LDL receptor levels on the cell surface, resuling in increased LDL clearance and lower circulating LDL levels. PCSK9 has not ascribed role in HDL biology. PCSK9 inhibitors are beign marketed as an alternative or add on to statin therapy, which itself is primarily an LDL reducing drug. Same thing with vytorin/ezetimibe....primarily a drug to lower LDL cholesterol, except ezetimibe inhibits intestinal cholesterol absorption. Same thing with the Phase II candidate ETC-1002 from Esperion.....primarily a drug to lower LDL cholesterol, except ETC-1002 inhibits chlolesterol synthesis (like statins) via a different mechanism. Personally, I think out of PCSK9 inhibitors/Ezetimibe/ETC-1002, that ETC-1002 has the greatest potential. However, the price of Esperion (ESPR) is kind of overvalued right now in my opinion.
Long story short, the target population for RVX-208 is going to be a low-HDL population, whereas the target population for statins/ezetimibe/PCSK9 inhibitors/ETC-1002 are primarily high LDL folks. There is no good HDL raising therapy in the clinic right now. RVX-208 or potentially the phase III CETP inibitor candidates anacetrapib and evacetrapib are the current best hope. So instead of comparing RVX-208 to these LDL-lowering therapies, one should be more worried about how the outcome of the CETP-inhibitor trials will affect the evaluation of RVX-208.
Welcome to the board, BTW.
Bear