Analyst Outlook
Praluent (alirocumab; Sanofi/Regeneron) is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PSCK9) and is intended for the treatment of hypercholesterolemia. PCSK9 is a protease involved in the intracellular and extracellular regulation of low-density lipoprotein receptor (LDLR) expression. It binds to the epidermal growth factor-like repeat A domain of the LDLR and targets the receptor for lysosomal degradation within the hepatocytes. PCSK9 is also known to increase the production of apolipoprotein B-containing lipoproteins. Praluent prevents circulating PCSK9 from binding to LDLRs, consequently inhibiting degradation. This allows the receptors to be recycled to the surface of hepatocytes, thus increasing plasma clearance of LDL-C.
Uptake of Praluent has been much lower than expected. Payers have put strict reimbursement restrictions on the availability of Praluent due to its high annual cost and lack of outcomes data, limiting its use to only the most high-risk patients. However, the combination of positive results from Praluent’s ODYSSEY cardiovascular outcomes trial (CVOT), and Sanofi and Regeneron’s announcement that they are willing to renegotiate larger rebates with insurers in return for the removal of prior authorization in high-risk patients, should increase uptake in this patient population. Additionally, the availability of data from the ODYSSEY CVOT will likely support the broadening of Praluent’s label to include use in primary hyperlipidemia patients who require additional LDL-C lowering.
Praluent (alirocumab; Sanofi/Regeneron) is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PSCK9) and is intended for the treatment of hypercholesterolemia. PCSK9 is a protease involved in the intracellular and extracellular regulation of low-density lipoprotein receptor (LDLR) expression. It binds to the epidermal growth factor-like repeat A domain of the LDLR and targets the receptor for lysosomal degradation within the hepatocytes. PCSK9 is also known to increase the production of apolipoprotein B-containing lipoproteins. Praluent prevents circulating PCSK9 from binding to LDLRs, consequently inhibiting degradation. This allows the receptors to be recycled to the surface of hepatocytes, thus increasing plasma clearance of LDL-C.
Uptake of Praluent has been much lower than expected. Payers have put strict reimbursement restrictions on the availability of Praluent due to its high annual cost and lack of outcomes data, limiting its use to only the most high-risk patients. However, the combination of positive results from Praluent’s ODYSSEY cardiovascular outcomes trial (CVOT), and Sanofi and Regeneron’s announcement that they are willing to renegotiate larger rebates with insurers in return for the removal of prior authorization in high-risk patients, should increase uptake in this patient population. Additionally, the availability of data from the ODYSSEY CVOT will likely support the broadening of Praluent’s label to include use in primary hyperlipidemia patients who require additional LDL-C lowering.
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