Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety.Common side effects include nasopharyngitis (cold), injection site reactions, and influenza.It was approved for medical use in the United States and in the European Union in 2015. Medical uses
Alirocumab is used as a second-line treatment to lower LDL cholesterol for adults who have a severe form of hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked. It is administered by subcutaneous injection. As of July 2015, it is not known whether alirocumab prevents early death from cardiovascular disease or prevents heart attacks; a clinical trial to determine outcomes was ongoing at that time, the results of which were expected in 2017. In November 2018, The New England Journal of Medicine published positive results from a clinical trial with alirocumab.
The antibody is distributed through the circulation, and it is eliminated at low concentrations by binding to its target, and at higher concentrations through a proteolytic pathway. Chemistry
Alirocumab is a human monoclonal antibody of the IgG1 isotype. It is made of two disulfide-linked human heavy chains, each disulfide-linked to a human light chain. It has an approximate molecular weight of 146 kDa.It is produced using Chinese hamster ovary cells transfected with recombinant DNA, that are grown in tanks. History
The importance of PCSK9 as a biological target for drug discovery emerged in 2003, when a series of discoveries led to identification of the protein and its gene, its role in causing some cases of familial hypercholesterolaemia when some mutations are present, and its role in causing very low levels of LDL cholesterol when other mutations are present.The discovery and validation of the target set off a race among pharmaceutical and biotech companies.Alirocumab was discovered by Regeneron Pharmaceuticals using its "VelocImmune" mouse, in which many of the genes coding for antibodies have been replaced with human genes. : 255–258   In an investor presentation, Regeneron claimed that with their system, it took only about 19 months from when they first immunized mice with PCSK9 until they filed their IND. : Slide 26    Alirocumab was co-developed with Sanofi under a deal made in 2007. Before it received its international nonproprietary name it was known as REGN727 and SAR236553.Phase 1 trial results were reported in 2012 in The New England Journal of Medicine.