What is Alirocumab?Alirocumab is an experimental drug for hypercholesterolemia.
Alirocumab works as an inhibitor (inhibitor) of the human enzyme proprotein convertase subtilisin / kexin type 9 - in short PCSK9. This is involved in the regulation of cholesterol metabolism. Regeneron Pharmaceuticals has developed Alirocumab.
Together with the company Sanofi, it has analyzed in Phase III studies (ODYSSEY) the potential application for the treatment of severe and familial hypercholesterolaemias. In four Phase III trials, alirocumab significantly reduced the levels of harmful LDL cholesterol in different patient populations.
In addition, the data obtained suggest that the PCSK9 inhibitor is also useful in treating cardiovascular impairments. Alirocumab was found to be well tolerated in the studies and had little side effects.
The enzyme PCSK9 regulates LDL cholesterol levels. It prevents the reuse of LDL receptors. The LDK receptors bound to the PCSK9 are degraded. Therefore, they do not return to the surface of the cells of hepatocytes to resorb the LDL cholesterol located there.
Conversely, PCSK9 inhibition promotes the reuse of LDL receptors. They can then continue to reduce LDL cholesterol through their cholesterol-binding ability. These now more available LDL receptors take up the harmful LDL cholesterol from the blood, so that the LDL cholesterol level drops.
Alirocumab should be injected subcutaneously every 14 days. The active ingredient has great additive effects to statins.
The innovative drug has been extensively and clinically tested with a variety of patient populations and in variable constellations. The 720 patients in the study were people treated with statins such as atorvastatin and rosuvastatin. 90% of the study participants had coronary heart disease (CHD) and about 30% had type 2 diabetes mellitus.
A randomized assignment of the participants in the ratio 2: 1 prescribed this therapy with alirocumab or with ezetimibe. Currently (February 2015) the 104-week study is still running. The intended goal of demonstrating the superiority of alirocumab has already been achieved. The drug lowered LDL baseline levels to an average of 50.6% at 24 weeks, while the ezetimibe control group only achieved a 21% reduction. With regard to the safety profile, both lipid lowering agents were equal.
Medical application & use
Alirocumab sets new standards in therapy for lowering elevated LDL cholesterol levels. Particularly at risk patients with LDL hypercholesterolaemia and a high cardiovascular risk should definitely try to reach a target value of less than 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. Patients with familial hypercholesterolemia, in particular, find it very difficult or impossible to achieve these goals. A high LDL cholesterol level is considered a direct cardiovascular risk factor. On average, however, the LDL cholesterol level of high-risk patients is 127 mg / dL.
To date, hypercholesterolemia has been treated with statins. Thus, the possible positive effect was limited from the outset, since a doubling of the dose of statin frequently only brings about a slight reduction in lipids. Unwanted side effects, especially on the muscles, also limited the options for increasing the dose.
Alirocumab closes the treatment gap that has arisen when statin therapy fails to dramatically lower LDL cholesterol levels in hypercholesterolaemic patients at risk and in patients with genetic hypercholesterolaemia. A mutation can be the cause in some people if LDL cholesterol is not sufficiently absorbed by the cells from the blood. Statins are inadequate - unlike alirocumab.
Risks & Side Effects
The new drug alirocumab is currently still at an experimental stage. It can also be successfully administered additively to statins. Alirocumab is well tolerated in the studies. Further research on the treatment with alirocumab remains to be seen. Currently (February 2015) a large-scale recruitment phase is in progress, the results of which are expected in 2018.