Over the next ten years, more than 15 million men worldwide Despite the tremendous potential of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, limited market access will restrict their impact on the cardiovascular (CV) disease prevention landscape beyond statins. Low-density lipoprotein (LDL)-cholesterol is one of the key risk factors for developing CV diseases, which are the leading cause of death globally. The compelling LDL-cholesterol lowering efficacy of the PCSK9 inhibitors means this novel class has the potential to revolutionize the management of hypercholesterolemia and dramatically reduce the risk of CV morbidity and mortality. Until late 2014, only the statins had recent, high-quality data showing that the reductions in LDL-cholesterol are associated with a reduction in CV event rates. Since then, the positive IMPROVE-IT results have reinforced the LDL-cholesterol lowering hypothesis, and hopes are high that the substantially more-efficacious PCSK9 inhibitors will induce even more clinically meaningful reductions in CV events. However, despite the leading PCSK9 inhibitor candidates having excellent risk-benefit profiles, the rapid development, high cost, injectable administration, and concerns about the antibody formulation will weigh negatively against these agents in the minds of key stakeholders, particularly until any CV benefits are confirmed.

Questions Answered in This Report:

  • Hypercholesterolemia is one of the most key modifiable risk factors for CV disease, but many patients with this lipid disorder are inadequately treated. How important is the emergence of the PCSK9 inhibitor class for managing hypercholesterolemia and for CV disease prevention?

  • There are several LDL-cholesterol lowering agents currently on the market and further novel treatments focusing on this lipid disorder are development. Where will the PCSK9 inhibitors fit into the treatment paradigm? How will later competition affect prescribing of these agents?

  • The PCSK9 inhibitors will be considerably more expensive than most competing drug classes. How do you think PCSK9 inhibitors will be reimbursed? How significant a barrier will cost be to accessing PCSK9 inhibitors?

  • Cardiovascular outcomes trials for the PCSK9 inhibitors are widely expected to demonstrate clinically meaningful benefits. How will positive CVOT data for the PCSK9 inhibitors influence prescribers and payers?
Author(s): Tim Blackstock, M.B. Ch.B., M.Phil.