An editorial notes that despite the effectiveness of cholesterol lowering drugs, most patients with familial hypercholesterolaemia cannot achieve plasma LDL cholesterol targets recommended to prevent cardiovascular events. The authors state that the recent development of monoclonal antibodies against PCSK9 might be considered a revolution in the treatment of familial and other types of hypercholesterolaemia. These drugs, injected subcutaneously every 15 or 30 days, bind to PCSK9 in plasma, reducing its concentration and thus enhancing intrahepatic cycling of the LDL receptor. Phase II and III studies showed reductions in LDL-C of 45–70% with alirocumab and evolocumab (two fully humanised PCSK9 monoclonal antibodies) in patients with heterozygous familial hypercholesterolaemia. The authors add that despite the short duration of the current studies of evolocumab reported in the Lancet, the findings are compatible with longer-term observations in other groups of patients with hypercholesterolaemia. Furthermore, if proven to be safe and efficacious in the long term, as well as cost effective, PCSK9 monoclonal antibodies might become the best standard of care for many patients with severe forms of familial hypercholesterolaemia. They speculate that use may also be widened to high-risk patients with polygenic hypercholesterolaemia, including those with statin myopathy. However, their wider application as an additional therapy to statins will depend on the results of large clinical outcome trials that are currently underway in patients at high risk of cardiovascular disease.
A Marketing Authorization Application for evolocumab for the treatment of high cholesterol was submitted to the EMA in September 2014.