A recent FDA advisory panel recommended the approval of 2 new agents in a novel class of cholesterol lowering drugs known as PCSK-9 inhibitors. What makes this remarkable is that these drugs illustrate all the promise and pitfalls of modern pharmaceutical development.
First, a little science. The target of the new drugs – a protein named proprotein convertase subtilisin/kexin type 9 (PCSK-9) – was discovered in 2001. Two years later, investigators reported that “gain-of-function” mutations in the gene that codes for PCSK-9 were associated with familial hypercholesterolemia and high rates of atherosclerotic vascular disease. Mutations of the gene that led to reductions in the function of PCSK-9 were associated with low LDL-cholesterol levels, and a lower incidence of vascular disease. That made the compelling case that PCSK-9 had a counter-regulatory function in LDL-cholesterol metabolism, so that interfering with its function would lead to lower cholesterol levels.