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