The PCSK9 Drugs — Epic success or epic failure?

This week, an FDA advisory committee recommended approval for the potent cholesterol-lowering drugs, evolocumab and alirocumab. The funny-sounding medications are called PCSK-9 inhibitor drugs. (Keep reading; I’ll tell you more.) Advisory committee members felt the benefits of the drugs outweighed the potential risks, especially in high-risk patients, such as those with Familial Hypercholesterolemia (FH). The FDA usually–but not always–follows the recommendation of the advisory committee. A final decision from FDA will come later this summer. In reading this piece, keep in mind that the goal of cholesterol drugs is to reduce the risk of heart attacks, strokes and death. It’s easy to get side-tracked into thinking a drug is good if it lowers cholesterol. Changing lab values is worthless unless those changes result in better outcomes in the future. I re-read both the Osler (evolocumab) and Odyssey (alirocumab) studies in the NEJM. This class of drugs and the story of their development is fascinating. PCSK9 Biology: We know that people with a rare DNA sequence variant in the gene encoding PCSK9 have very low LDL levels and low rates of heart disease. So what do you do? You develop a monoclonal antibody to simulate the favorable genetic variant. That’s exactly what the makers of the PCSK9 inhibitors have done. And it’s nifty biology. But the clinical science is early. So very early. The PCSK9 story turns on the LDL hypothesis: The concept that lowering...
Source: Dr John M - Category: Cardiology Authors: Source Type: blogs