Alirocumab

• CAS Number: 1245916-14-6

Alirocumab (also REGN727 / SAR236553 ) is an experimental drug antihypercholesterolemic from the group of monoclonal antibodies.

Properties

Alirocumab acts as an inhibitor (inhibitor ) of the human enzyme PCSK9 ( proprotein convertase subtilisin / kexin type 9 ), which is involved in the regulation of cholesterol metabolism. It was developed by Regeneron Pharmaceuticals and examined in collaboration with Sanofi in Phase III clinical trials for use in the treatment of severe and familial hypercholesterolemia.

Mechanism of Action

PCSK9 binding to the LDL receptor (LDL -R) and is amplified with that of liver cells was added. By PCSK9 binding endocytosis and degradation of the LDL receptor is promoted in the endosomes. This means that fewer LDL receptors for recirculation to the cell surface are available, whereby the binding of LDL cholesterol decreases (so-called " bad cholesterol "). As a monoclonal antibody inhibiting the PCSK9 - specific serum Alirocumab binds PCSK9, whereby the formation of LDL receptor and PCSK9 complexes to intracellular degradation of the LDL receptor can be prevented. More LDL cholesterol can be absorbed by the LDL receptors and degraded in the cell.

This mechanism of action is also based on the experimental drugs Evolocumab and Bococizumab.

Clinical Development

In 2003 it was shown that gain - of-function mutations in the PCSK9 gene may be associated with hypercholesterolemia and loss-of- function mutations with low LCL cholesterol plasma levels and low risk for coronary heart disease are connected.

In May 2013 Manfred Schubert - Zsilavecz presented at the Pharmacon Merano Alirocumab ago as the most developed PCSK9 inhibitors. Alirocumab is a vollhumanisierter anti - PCSKA9 monoclonal antibody. 2011, the first phase I studies were conducted with Alirocumab: In 15 patients with familial and non - familial hypercholesterolemia, an additional reduction in LDL cholesterol of 40 % to 60 % could be achieved with Alirocumab subcutaneously within 2 months after pre-treatment with statins. 152 patients with persistently elevated LDL - cholesterol despite treatment with atorvastatin ( LDL cholesterol ≥ 100 mg / dL / ≥ 2.5 mmol / L) were treated with increasing subcutaneous Alirocumab injections: Short it is also conducting Phase II results were known every 2 or 4 weeks, treated. An additional reduction in LDL cholesterol of 40% to 72 % was observed after 3 months, as where the LDL cholesterol levels of patients treated with atorvastatin alone ( placebo group ) decreased by only 5 %.

Few side effects were observed. However, the number of patients studied is still limited.

These positive results are now reviewed on a large scale in different patient groups in detail. In particular, patients come into question with primary hypercholesterolemia, despite standard therapy ( eg statins) increased LCL cholesterol levels have, and patients with high cardiovascular risk. As of October 2013 twelve phase III trials were already created and some of them already underway to investigate the efficacy and safety and to allow for future marketing authorization.