Alirocumab is an experimental drug for hypercholesterolemia. It is one of the monoclonal antibodies. Alirocumab was introduced in May 2013 at “Pharmacon Meran” by Austrian scientist Manfred Schubert-Zsilavecz.
What is alirocumab?
Alirocumab is an experimental drug for hypercholesterolemia. Alirocumab functions as an inhibitor (inhibitor) of the human enzyme proprotein convertase subtilisin/kexin type 9 – PCSK9 for short. This is involved in the regulation of cholesterol metabolism. The company Regeneron Pharmaceuticals has developed alirocumab. Together with Sanofi, it has analyzed its potential use in Phase III studies (ODYSSEY) for the treatment of severe and familial hypercholesterolemia. In four Phase III trials, alirocumab was shown to significantly reduce harmful LDL cholesterol levels in different patient groups. In addition, the data obtained suggest that the PCSK9 inhibitor is also suitable for treating cardiovascular impairment. In the studies, alirocumab was shown to be well tolerated for this purpose and to have few side effects.
Pharmacologic Effects
The enzyme PCSK9 regulates LDL cholesterol levels. In doing so, it prevents the reuse of LDL receptors. The LDL receptors bound to PCSK9 are degraded. Therefore, they do not rejoin the surface of the cells of hepatocytes to reabsorb the LDL cholesterol located there. Conversely, PCSK9 inhibition promotes the reuse of LDL receptors. They can then further reduce LDL cholesterol via their cholesterol-binding ability. These LDL receptors, which are now more available, take up the harmful LDL cholesterol from the blood, so that LDL cholesterol levels fall. Alirocumab is to be injected subcutaneously every 14 days. The active ingredient has major additive effects to statins. The innovative drug has been extensively tested clinically with different patient populations as well as in variable constellations with great success. The 720 patients in the study were individuals treated with statins such as atorvastatin and rosuvastatin. Ninety percent of the study participants had coronary artery disease (CAD), and approximately 30% had type 2 diabetes mellitus. A randomized 2:1 allocation of participants assigned them to treatment with alirocumab or ezetimibe. Currently (February 2015), the 104-week study is still ongoing. The objective of demonstrating the superiority of alirocumab has already been achieved. The drug reduced baseline LDL levels to an average of 50.6% after 24 weeks, while the comparison group with ezetimibe only achieved a reduction of 21%. In terms of safety profile, both lipid-lowering agents were on par.
Medical Application and Use
Alirocumab sets new standards in therapy for lowering elevated LDL cholesterol levels. Patients at particular risk mt LDL hypercholesterolemia and high cardiovascular risk should definitely try to achieve a target value of below 100 mg/dL or < 2.6 mmol/L. Patients at extra-high risk are even advised to get below 70 mg/dL or < 1.8 mmol/L. In particular, patients with familial hypercholesterolemia find it very difficult or impossible to achieve these targets. In this context, a high LDL cholesterol level is considered a direct cardiovascular risk factor. However, on average, the LDL cholesterol level of high-risk patients is 127 mg/dL. Until now, hypercholesterolemia was treated with statins. Thus, the potential beneficial effect was limited from the outset, since doubling the statin dose often yields only a small lipid reduction. Unintended side effects, mainly on muscle, also limited the options for increasing the dose. Alirocumab fills the treatment gap that opened up when statin therapy failed to dramatically lower LDL cholesterol levels in high-risk patients with hypercholesterolemia and patients with genetic hypercholesterolemia. A mutation can be the cause in some people when LDL cholesterol is not sufficiently reabsorbed by the cells from the blood. Statins have an insufficient effect in this case – in contrast to alirocumab.
Risks and side effects
The new drug alirocumab is currently still at the experimental stage.It can also be successfully administered as an additive to statins. Alirocumab is proving to be well tolerated in the studies. Further research results on treatment with alirocumab are awaited. Currently (February 2015), a large-scale recruitment phase is underway, with results expected in 2018.
