Repatha mechanism of action
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Summary
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These studies suggest Repatha (evolocumab) is a PCSK9 inhibitor that lowers LDL-cholesterol levels by 50-60% in patients with hypercholesterolemia, especially when used alongside statin therapy.
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Mechanism of Action of Repatha (Evolocumab)
Introduction to Repatha and PCSK9 Inhibition
Repatha, also known by its generic name evolocumab, is a fully human monoclonal antibody developed by Amgen. It is primarily used for the treatment of hypercholesterolemia, particularly in patients who are unable to achieve their LDL-C (low-density lipoprotein cholesterol) targets with other lipid-lowering therapies alone . Repatha functions by inhibiting the activity of proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that plays a crucial role in cholesterol metabolism .
Role of PCSK9 in Cholesterol Metabolism
PCSK9 is a circulating enzyme secreted by the liver that regulates the number of LDL receptors (LDL-R) on the surface of liver cells. Normally, LDL-Rs bind to LDL-C particles and remove them from the bloodstream. However, when PCSK9 binds to LDL-Rs, it leads to their degradation in lysosomes rather than their recycling back to the cell surface. This results in fewer LDL-Rs available to clear LDL-C from the blood, leading to higher levels of LDL-C.
Mechanism of Action of Evolocumab
Evolocumab works by specifically binding to PCSK9, thereby preventing it from interacting with LDL-Rs. This inhibition allows more LDL-Rs to be recycled to the liver cell surface, increasing the clearance of LDL-C from the bloodstream and significantly lowering blood LDL-C levels . Clinical studies have shown that evolocumab can reduce LDL-C levels by up to 60% when used in conjunction with statins or as monotherapy in statin-intolerant patients .
Clinical Efficacy and Safety
Evolocumab has been extensively studied in controlled clinical trials, demonstrating its efficacy in significantly reducing LDL-C levels, total cholesterol, non-HDL cholesterol, apoprotein B, and lipoprotein(a). It is administered via subcutaneous injection, either every two weeks or once a month, and has been approved for use in various populations, including those with heterozygous and homozygous familial hypercholesterolemia. The safety profile of evolocumab is favorable, with no significant adverse effects on cognitive function or other serious side effects reported in clinical trials.
Conclusion
Repatha (evolocumab) represents a significant advancement in the management of hypercholesterolemia through its novel mechanism of action as a PCSK9 inhibitor. By preventing the degradation of LDL receptors, it enhances the liver's ability to clear LDL-C from the bloodstream, offering a potent option for patients who require additional LDL-C lowering beyond what is achievable with traditional therapies alone .
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