Evolocumab (Repatha™) is a fully human monoclonal antibody developed by Amgen that has been approved as a treatment for hypercholesterolaemia in the EU, and is awaiting approval in the USA and Japan. It specifically binds proprotein convertase subtilisin/kexin type 9 (PCSK9)—a negative regulator of low-density lipoprotein (LDL)-receptors—thereby improving the ability of the liver to bind LDL-cholesterol (LDL-C), leading to reduced LDL-C blood levels. The drug reduces LDL-C levels in patients with hypercholesterolaemia when used as monotherapy or in conjunction with a statin. This article summarizes the milestones in the development of evolocumab leading to this approval for the treatment of adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet with or without a statin and/or other lipid lowering therapies, and in adults and adolescents aged ≥12 years with homozygous familial hypercholesterolaemia in combination with other lipid lowering therapies.
KeywordsStatin Therapy Ezetimibe Lipid Lowering Therapy Familial Hypercholesterolaemia Primary Hypercholesterolaemia
The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. A. Markham is a contracted employee of Adis, Springer SBM.
- 1.European Medicines Agency. Repatha (evolocumab): EU summary of product characteristics. 2014. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003766/WC500191398.pdf. Accessed 4 Aug 2015.
- 2.Amgen, Astellas Pharma. Amgen and Astellas announce Japan alliance [media release]. 29 May 2013. http://www.amgen.com.
- 3.Dias CS, Shaywitz AJ, Wasserman SM, et al. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol. 2012;60(19):1888–98.CrossRefPubMedGoogle Scholar
- 4.Emery MG, Gibbs JP, Slatter JG, et al. Evolocumab pharmacokinetics and its effects on LDL-C and PCSK9 lowering in subjects with mild or moderate hepatic impairment [abstract no. PII-034]. Clin Pharmacol Ther. 2015;97:S69.Google Scholar
- 5.Gibbs JP, Grover A, Emery MG, et al. Impact of target-mediated elimination on evolocumab dose and regimen [abstract no. 422]. In: European Atherosclerosis Society Annual Congress 2015. 2015.Google Scholar
- 6.Wasserman SM, Koren MJ, Giugliano RP, et al. Evaluation of the relationship between evolocumab 140 mg every two weeks and 420 mg monthly dosing regimens [abstract no. 16270]. Circulation. 2014;130(Suppl 2):A16270.Google Scholar
- 11.Giugliano RP, Desai NR, Kohli P, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. 2012;380(9858):2007–17.PubMedCentralCrossRefPubMedGoogle Scholar
- 15.Koren MJ, Scott R, Kim JB, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2012;380(9858):1995–2006.CrossRefPubMedGoogle Scholar
- 18.Raal F, Hovingh K, Blom D, et al. Long-term treatment with evolocumab in patients with homozygous familial hypercholesterolaemia (HoFH): interim results from the trial assessing long-term use of PCSK9 inhibition in subjects with genetic LDL disorders (TAUSSIG) study [abstract no. 1042]. In: 17th International Symposium on Atherosclerosis. 2015.Google Scholar
- 19.Raal F, Scott R, Somaratne R, et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012;126(20):2408–17.CrossRefPubMedGoogle Scholar