PCSK9 inhibitors: a non-statin cholesterol-lowering treatment option

ABSTRACT

Elevated low-density lipoprotein cholesterol (LDL-C) plays a major role in the development of atherosclerotic cardiovascular disease. Statins are the first-line treatment to lower LDL-C in patients with hypercholesterolemia; however, some high cardiovascular risk patients may have inadequate responses to statin therapy or are intolerant to statins, and may need additional and/or alternative non-statin therapies to further reduce their LDL-C levels. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of circulating LDL-C levels, have received considerable attention as promising non-statin therapeutic options for the management of hypercholesterolemia. This review provides a brief overview of the history and science of PCSK9 inhibitors, focusing on two PCSK9 monoclonal antibodies that have been approved by the US Food and Drug Administration: alirocumab and evolocumab. Recently released and forthcoming clinical trial data will be discussed, as well as the practical application of patient populations that may benefit from PCSK9 inhibitors. Finally, the recent expert recommendations regarding the use of PCSK9 inhibitors and other non-statin therapies to treat patients with inadequate LDL-C-lowering on statin therapy will be summarized.

KEYWORDS:

• Alirocumab
• evolocumab
• LDL-C
• PCSK9 inhibitors
• statin

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Acknowledgments

The author would like to thank Dr James Underberg for his contributions to the early conceptualization and development of this manuscript. Medical writing and editorial support in the preparation of the initial drafts of this publication under the guidance of the author was provided by Nicole Neel, PhD of MicroMass Communications, Inc. (Cary, NC); medical writing and editorial support in the preparation of the later drafts and the final version of this publication under the guidance of the author was provided by Grace Shim, PhD of Prime (Knutsford, UK), all funded by Sanofi US (Bridgewater, NJ) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY) according to Good Publication Practice guidelines (Link).

Declaration of interest

GSP has served as a consultant for Kowa Pharmaceuticals America, Inc. and Amarin. He has also served as a speaker for Amarin, Amgen, Regeneron Pharmaceuticals, Inc., Sanofi, and True Health Diagnostics Labs. A Postgraduate Medicine peer reviewer on this manuscript declares that they have received research grants and consultancy fees from manufacturers of PCSK9 inhibitors, ezetimibe, and statins. Other peer reviewers on this manuscript have no relevant financial relationships to disclose.

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Funding

Support for this article was provided by Sanofi US (Bridgewater, NJ) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY). Employees of Sanofi US and Regeneron Pharmaceuticals, Inc. were permitted to review the manuscript and offer comments. However, the author was responsible for all content and editorial decisions, and received no honoraria related to the development of this publication.