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Dyslipidaemia

The PCSK9 adventure — humanizing extreme LDL lowering

Nature Reviews Cardiology volume 14, pages 319–320 (2017)Cite this article

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PCSK9 inhibitors are the most potent LDL-cholesterol lowering drugs on the market. The latest cardiovascular outcome trials of these anti-PCSK9 monoclonal antibodies show positive results with fully-human antibodies, although with modest effect on major adverse cardiovascular events in patients who attain LDL-cholesterol target levels with statin therapy, whereas humanized antibodies are associated with the development of neutralizing antibodies.

Refers to Ridker, P. M. et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1701488 (2017) | Ridker, P. M. et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1614062 (2017) | Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1615664 (2017)

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Figure 1: Fully-human versus humanized therapeutic monoclonal antibodies.

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Acknowledgements

M.D.S. and S.F. were supported partially by NIH grant R01HL132985. The authors gratefully acknowledge Ms Deanna Plubell for assistance with the figure.

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Authors and Affiliations

  1. Michael D. Shapiro and Sergio Fazio are at Knight Cardiovascular Institute, Center for Preventive Cardiology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.,

    Michael D. Shapiro & Sergio Fazio

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  1. Michael D. Shapiro
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  2. Sergio Fazio
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Correspondence to Michael D. Shapiro or Sergio Fazio.

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Competing interests

M.D.S. received compensation for advisory activities from Alexion, Amgen, Bracco, and GE Healthcare. S.F. received compensation for advisory activities from Aegerion, Amarin, Amgen, Kowa, Merck, and Sanofi.

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Shapiro, M., Fazio, S. The PCSK9 adventure — humanizing extreme LDL lowering. Nat Rev Cardiol 14, 319–320 (2017). https://doi.org/10.1038/nrcardio.2017.66

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