Orange, this is all conjecturing and discussion. There is a way to slant anything and things will come out as they do no matter what anyone here says. In regards to cancer, I didn't say anything except that the article did show a number that seemed to be much larger for CA in the treated group than in the untreated group. If you want to tie that into the immune system then OK, so be it. I do think that the HDL molecule is very complex in what it does, how it functions, the various forms it takes, and consequences remain to be determined. IMO, you extrapolate about the benefits of supraphysiologic levels of artificially increased levels of HDL just as bad as the rest of us with our seeming "blind" devotion to Mipo. As far as dialysis patients, I stand by my prediction that I think Mipo will outperform a drug like a PCSK9 inhibitor in patients with stage V kidney disease. When you look at these patients, the patients with the worse prognosis have the lowest LDL levels. That is because their bodies upregulate LDL receptors in the endothelium and yes you do have a lower LDL in the blood.....but where is that LDL going, there's a price to pay for that. It is going to the very place you don't want it to, that being the endothelium. As far as HDL is concerned in dialysis patients, if you take their HDL it does not act like regular HDL. It doesn't work. If you take a dialysis patient and use a different subjects HDL in vitro it does work. Will increasing noneffective HDL in dialysis patients make it work better? I don't know, do you? What do PCSK9 inhibitors do? Statin drugs have not done too well in stage IV and stage V CKD patients. PCKS9 drugs may just accentuate the statin drug effect in this patient population. Also, If PCSK9 inhibitors don't do well in patients with uncontrolled diabetes mellitus where are these patients to turn to try and get beyond that 25% reduction with statins in lowering their CV risk(which is really much much higher)? Also, look at how many DM type II patients are actually really controlled with their DM Type II.....not good numbers. So how many patients in this category will really be patients to benefit from PCSK9 inhibitors if the aforementioned variables are true? How many patients have both CKD and uncontrolled DM Type 2 Superimpose on that the fact that the disease is growing in epidemic proportions. Getting back to the HDL, I put it back to you Orange, How do you know that just willy-nilly increasing HDL with an artificial method will definitely work in anybody, much less these individuals with preexisting very poor health? We've seen good numbers in cherry-picked patients. Now I'd like to see the other side of the street. I personally also can't believe that the FDA will let the CETP inhibitors off as easy as you think. Think about it, if one of your colleagues told about five years ago that fenofibrates and niacin were maybe not at all that useful, would you have believed them? Those two compounds/class may have to do repeat FDA studies. If they do, if the FDA keeps on pounding the diet drugs, especially one that has both drugs already approved separately, how can you be so sure when you're dealing with a class that has had six or seven failures already? What about Mipo? Well what about Mipo, it has been given value of nearly zero, so anything above that will be a benefit for ISIS investors. So if I'm one of those people like the ones that believed in fenofibrates and niacin and I'm wrong I'll just have to live with it. But I do have Endspeed's slides to draw inspiration from, and the still not violated rule of everything seen in rats, has been seen in humans in regards to benefits from Mipo.
Also, getting back to price. I see it everyday, price does matter and these people you deal with at insurance companies don't seem to have any interest or expertise to tease out details to really help patients. If Mipo and the MTP inhibitor both get approved and the MTP inhibitor is three times the cost, no insurance will cover it first line NO MATTER WHAT. Those patients will have to have failed Mipo first and have it documented fully. The MTP inhibitor will be a victim of its own success when the CEO thought he could push the price. Also, with medicines this expensive, such as Xolair.....you miss your dosing, or are documented as being poorly adherent and the insurance company will drop your privilege to get the med any further. They aren't going to let have you have empty soon to expire vials in your refrigerator and be sending you more. Then the issue is cost vs. different classes of medicines. I don't know what the PCSK9 drugs are going to cost. But if they cost what I think, then....I also believe the insurance companies will say you have to fail Mipo first if there is a huge price discrepancy. Maybe I'll be wrong, but it is out there everyday with price and trying to fit the square peg in the round hole drug formulary insurance coverage style. As far as malpractice is concerned, any family that has a patient with HeF that dies could find a lawyer and say the doctor didn't get a consult with a lipidologist and if they had their family member would still be here today. That drawing up a distinction of a severe HeF vs. not severe HeF if a patient is already dead will be hard to defend.
IMO you may have abandoned Mipo too soon, but maybe I'll be wrong, that is what makes a market. But what also makes a market is doing all the studies, making the grade, and making the insurance carrier cost grade, so fancy new meds beware of cheaper "inferior" products for the same indication. And hey, I hope that the Factor XI drug and the ApoCIII inhibitor are more successful than Mipo, I hope there are 100 ISIS drugs more successful than Mipo. t