Cardiovascular disease is the leading cause of death in the world with its prevalence directly tied to amount of cholesterol in the blood. The Framingham Heart Study showed the tie between high cholesterol and heart disease. The study found that low density lipoprotein (LDL) was more predictive of heart disease than total cholesterol. The study also suggested that family history made the cause of hypercholesterolemia and not a high just a high fat diet. The pharmaceutical class, HMG Co Reductase inhibitors (also known as “statins”) came on the market in 1987 and significantly changed the treatment of hypercholesterolemia. Although statins are responsive, they do carry risk as reports of myopathy and even fatal rhabdomyolysis led to some statins
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They discovered a genetic mutation that caused high levels of an enzyme now called proprotein convertase subtilisin kexin type 9 (or PCSK9) that binds to the LDL receptor (what processes LDL cholesterol from the blood) and degrades it in the liver. People who have high levels of this enzyme, have high levels of LDL in the blood because the enzyme degraded the receptors and the LDLs now nowhere to go to be processed. Because this enzyme works outside of cells, any active pharmaceutical ingredient would be susceptible an immune response. Therefore, a monoclonal antibody biological drug was the only pathway to target this enzyme to increase the amount of LDL receptors.
Evolocumab by Amgen, Inc. is a human monoclonal antibody directed against PCSK9. Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the LDL receptor, preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL levels. Evolocumab was developed under the name AMG 145 and marketed under the name
They discovered a genetic mutation that caused high levels of an enzyme now called proprotein convertase subtilisin kexin type 9 (or PCSK9) that binds to the LDL receptor (what processes LDL cholesterol from the blood) and degrades it in the liver. People who have high levels of this enzyme, have high levels of LDL in the blood because the enzyme degraded the receptors and the LDLs now nowhere to go to be processed. Because this enzyme works outside of cells, any active pharmaceutical ingredient would be susceptible an immune response. Therefore, a monoclonal antibody biological drug was the only pathway to target this enzyme to increase the amount of LDL receptors.
Evolocumab by Amgen, Inc. is a human monoclonal antibody directed against PCSK9. Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the LDL receptor, preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL levels. Evolocumab was developed under the name AMG 145 and marketed under the name