This is the (proprotein convertase subtilisin-kexin type 9) PCSK9 monoclonal-antibody inhibitor that increases the ability of the liver to clear low-density-lipoprotein cholesterol (LDL-C).
According to results of the LAPLACE-2 trial -presented on March 30 during the ACC 2014 in Washington, USA-, the monoclonal antibody (mAb) evolocumab produced significant reductions in LDL-C as an add-on to statins in all treatment groups.
This was a 12-week study conducted between January and December of 2013, and included patients with primary hypercholesterolemia and mixed dyslipidemia. Patients were randomized to a moderate-intensity statin dose (atorvastatin 10 mg, simvastatin 40 mg, or rosuvastatin 5 mg), or high-intensity statin dose (atorvastatin 80 mg, rosuvastatin 40 mg). After a four weeks period of lipid stabilization, 1,899 patients were randomized to one of 24 treatment arms to compare subcutaneous evolocumab (140 mg every two weeks or 420 mg every four weeks) with matching placebo (every two or four weeks) or ezetimibe (10 mg daily; atorvastatin patients only) when added to statins.
All groups treated with the mAb evolocumab showed highly significant reductions in LDL-C compared with placebo: 66% – 75% on evolocumab injections regimen every 2-week, and 63% – 75% on a 4-week regimen. Most patients (86% – 94%) in the moderate-intensity statin groups and also (93% – 95%) in the high-intensity groups, achieved an LDL-C level of <70 mg/dL. Ezetimibe reduced LDL-C by 19% – 22%.
Evolocumab on top of moderate-intensity statin plan reduced LDL-C levels between 39 mg/dL to 49 mg/dL and between 33 mg/dL to 39 mg/dL with high-intensity statin medication. Additionally evolocumab also significantly reduced non-HDL-C, apo B and Lp(a) levels. Regarding safety and tolerability, there were no significant differences between groups (evolocumab, placebo-, and ezetimibe treated patients).
In summary, when combined with atorvastatin, LDL-C lowering was significantly greater in patients receiving evolocumab (63-75%) versus those receiving ezetimibe (19-32%).
“Many patients can’t tolerate high-intensity statins and cannot achieve desired LDL reductions with moderate or low-intensity statins, and those with high cholesterol levels often need more than high-intensity statins to lower LDL levels adequately,” said Jennifer G. Robinson, the author of Laplace 2 and stated that evolocumab may be useful for these patients.
This is a very exciting class of drugs. There are several studies using this kind or medications that seem to be safe and effective in the reduction of LDL-C levels dramatically. Long-term studies driven by cardiovascular hard en-points (Fourier, Odyssey, Spire) are currently running.