PCSK9 Drugs

Sanofi and Regeneron report "POSITIVE RESULTS" with Alirocumab (anti-PCSK9) from their first phase III clinical trial for LDL Cholesterol Reduction. LDL is the bad cholesterol, HDL is the good. These terms are unfortunate since the body has deemed both forms as necessary. Over time the body may build up LDL which is an indication that you are not regulating your diet and exercise properly. LDL cholesterol can build up on the walls of your arteries and increase your risk of heart disease. However we have to wonder how to interpret the accepted medical stance on cholesterol. 

In Good Calories, Bad Calories, Gary Taubes gives a history of cholesterol research. Not everyone agrees with the current information on cholesterol levels and the role cholesterol plays. The way in which some minds work is that if something is bad, it should be eliminated. That works fine if you are talking about crime in your neighborhood. But LDL is there for a reason. It is coded into our DNA. The question then is the range in which a healthy individual maintains LDL levels. If BigPharma wants to make drugs to help sick people mimic healthy people with regards to LDL levels, what is their goal? 

The mean low-density lipoprotein cholesterol (LDL-C, or bad cholesterol) reduction from baseline to week 24, the primary efficacy endpoint of the study, was significantly greater in patients randomized to ezetimibe (47.2% vs. 15.6, p < 0.0001)

Back to the concept of an accepted range. If their is a level too high there is a level too low. What does the 47.2% reduction in LDL from alirocumab vs 15.6% reduction from ezitimibe (Zetia) mean? One goal of Regenerons research is to determine  the lowest effective dose of anti-PCSK9 antibody. The reasons for this are best summed up by these findings.

The percentage of patients who reported treatment emergent adverse events was 78.4% in the ezetimibe group and 69.2 in the alirocumab group. The most common class of adverse events was infections (39.2% with ezetimibe vs 42.3% with alirocumab), which included nasopharyngitis, influenza, and upper respiratory tract infection. 

Like cholesterol, there is the good and the bad. We see that anti-PCSK9 products can lower LDL-C. They did not say if the people felt better or got healthier. They did not say if they could more easily and safely adjust a persons LDL levels into the range found in healthier people. The just lowered the bad. In the process they increased a range of infections that can be deadly to older people.

Check out this article on the dangers of PCSK9 targeted drugs. "New Cholesterol Drug PCSK9 Likely Is to Prematurely Kill You". If lowering you LDL levels is the good news, this has got to be the bad. Dr. Mercola brings up a few topics the Regeneron press release does not. There is a lower limit not to be crossed. Lowering your LDL levels to below 50 is dangerous. Your body needs cholesterol to produce hormones, cell membranes, vitamin D, and bile acids that help you digest fat. The most effective method of regulating your cholesterol profile is through diet and exercise. That's the good news. What about this added downside of dropping dead from anti-PCSK9?

Again we get the lower limit discussion that Regeneron has omitted from their world view of cholesterol. According to Dr. Mercolas' article, low HDL can lead to poor memory and a decline in memory for middle aged people. You may also experience violent behavior and aggression,  depression, suicide, cancer, Parkinsons disease, and heart disease. Dr. Mercola states that the odds are greater than 100 to 1, that if you are taking a statin to lower your cholesterol, you really don't need it. Statins are what the PCSK9 drugs are going to compete against.

Statin drugs, which one in four adults over 45 are using to protect their heart health, can paradoxically have significantly detrimental effects on your heart health 

Our understanding (our science) of cholesterol has been touched by the Cargo Cults. We have to look into these things that don't work and ask why. Not only do we muddy the waters with bad and biased pharmaceutical research, we create dangerous products for the most vulnerable. I think it is fairly clear that cholesterol research needs to be revisited, new guidelines need to be established and diet and exercise needs to be advertised. PCSK9 should be studied very carefully to make sure it does not reduce your own ability to fight heart disease and worse, to simply kill you. In my Utopia, all future studies would include a diet and exercise arm. If that were the case I am sure they would halt the study and never again allow a statin or anti-PCSK9 enter the body of a person capable of eating healthier and increasing their level of exercise.