RE: RE: RE: Pfizer-geddon - One Man's ViewpointYes, CETP is where the confusion lies. A lot of people think that the torcetrapib compound was why Pfizer bought Esperion and paid so much for it... to remove it from the market, but No, I do not work for Pfizer or Esperion but know both companies as well as the HDL market very well. The comparison I made to atherogenics is that atherogenics was also a small molecule compound that had shown some hints of plaque regression. It was a VCAM-1 inhibitor and thus also anti-inflammatory. They did not go under due to bankruptcy but rather due to their phase II trial failing to meet its primary endpoints of plaque reduction despite meeting secondary endpoints of a statistically significant reduction in acute ischemic events due to the anti-inflammatory properties. While the $300 million seems like a lot, it unfortunately is not that much in this world and the current debt portion would have been restructured if they had met their primary endpoints. The reason I compare them is because RVX also has similar anti-inflammatory properties and has shown hints of plaque regression. If I had to design a trial, I would choose a reduction in ischemic events over simple plaque reduction. It's not that plaque reduction isn't a good thing. In concept it is, but there is not agreement on how much plaque reduction you would need and even if 5% would also correspond to reduced events or mortality. Absent of that and it really doesn't matter much. I also would not choose IVUS but rather would go with OCT. The spatial orientation difference between the two is almost 2 orders of magnitude meaning with OCT you would see even the most basic of plaque changes. With regard to how much apoa-1, herein lies the problem. All of the apao-1 alone studies or rHDL studies have used significant doses of apao-1 to show their effects. Even the low dosing of 10-15 mg/kg is way above what you will see with these transcription factors. Apoa-1 alone I see as an acute therapy primarily for ACS due to the cost of production and the likelihood of diminishing returns due to the type of plaque it is most effective on. Now with RVX, it is possible that a small increase in apao-1 seen uniformly on a daily basis over several weeks will also have an effect. This is certainly possible but the increases seen in circulating apoa-1 levels is similar to that which is seen with high dose niacin/B3. This is why I come back to the anti-inflammatory properties being the key. Imagine a dug taken once a day after a heart attack that will reduce your chances of a follow-up event. Its a blockbuster independent of plaque regression. These changes can be seen with a relatively small number of patients. Forget about the combination statin route. This is good for the big pharmas but not a trial that RVX can run. The changes are too small which means the trial size will be quite large. I still like RVX and always like the underdog in the biotech world. Just my opinions.