Update on pcsk9 inhibitors and new therapies

Proprotein convertase subtilisin/kexin type 9 (PCSK9), first described in 2003, binds to the low-density lipoprotein receptor (LDLR) resulting in its degradation. Inhibition of PCSK9 results in increased LDLR recycling and a reduction in LDL-cholesterol (LDL-C). The clinical development of monoclonal antibodies (mAbs) that bind to circulating PCSK9 has been rapid with large phase II and III trials demonstrating substantial reductions in LDL-C when given to a very broad group of patients including those with familial and non-familial hypercholesterolemia, diabetes, heart disease, and in those intolerant to statins. Despite sub-cutaneous administration these mAbs are well tolerated and have demonstrated good safety. Two agents, alirocumab and evolocumab, received regulatory approval in 2015 in the US and Europe and evolocumab in 2016 in Japan.