**8.1. PCSK-9 inhibitors**

Recently, it has been published in *Circulation* that AMG145, the monoclonal antibody against PCSK-9 from Amgen®, at a dose of 105 mg Q2W reduced plasma Lp(a) levels on average by 32% [33]. At this dose, the authors observed a reduction of plasma LDL-C and of apoB by 60% and 50%, respectively. It must be stressed, however, that among the 626 male and female patients, approximately half of them had Lp(a) levels below the median concentration of 43 nmol/L. Although the Lp(a)-lowering effect of AMG-145 correlated significantly with the reduction of LDL-C, patients with low Lp(a) showed a much bigger relative reduction of Lp(a) than patients of the 3rd or 4th Lp(a) quartile. At a dosage of 420 mg, Q4W patients of the 4th quartile did not respond at all with a reduction of Lp(a). According to unconfirmed commu‐ nications AMG-145 might be registered in the 2nd half of 2015, yet the treatment costs will certainly be significantly higher as compared to that of statin therapy.

In a similar study with SAR236553, the PCSK-9 antibody from Sanofi®, an average reduction of Lp(a) of up to 28.6% was observed [34].We actually consider these trials as pilot studies as they do not address all the questions of the mode of action of PCSK-9 inhibitors on Lp(a). It is well known that these drugs increase the activity of LDL-R, particularly in the liver, and this receptor has a relatively low affinity to Lp(a).
