Systematic review of published Phase 3 data on anti-PCSK9 monoclonal antibodies in patients with hypercholesterolaemia

Ioanna Gouni-Berthold, Olivier S Descamps, Uwe Fraass, Elizabeth Hartfield, Kim Allcott, Ricardo Dent, Winfried März, Ioanna Gouni-Berthold, Olivier S Descamps, Uwe Fraass, Elizabeth Hartfield, Kim Allcott, Ricardo Dent, Winfried März

Abstract

Aims: Two anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, alirocumab and evolocumab, have been approved for the treatment of hypercholesterolaemia in certain patients. We reviewed data from Phase 3 studies to evaluate the efficacy and safety of these antibodies.

Methods: We systematically reviewed Phase 3 English-language studies in patients with hypercholesterolaemia, published between 1 January 2005 and 20 October 2015. Congress proceedings from 16 November 2012 to 16 November 2015 were also reviewed.

Results: We identified 12 studies of alirocumab and nine of evolocumab, including over 10 000 patients overall. Most studies enrolled patients with hypercholesterolaemia and used anti-PCSK9 antibodies with statins. The ODYSSEY FH I, FH II and HIGH FH alirocumab studies and the RUTHERFORD-2 evolocumab study exclusively recruited patients with heterozygous familial hypercholesterolaemia. Two evolocumab studies focused mainly on homozygous familial hypercholesterolaemia (HoFH): TESLA Part B and TAUSSIG (a TESLA sub-study); only those data for HoFH are reported here. All comparator studies demonstrated a reduction in LDL cholesterol (LDL-C) with the anti-PCSK9 antibodies. No head-to-head studies were conducted between alirocumab and evolocumab. Up to 87% of patients receiving alirocumab and up to 98% receiving evolocumab reached LDL-C goals. Both antibodies were effective and well tolerated across a broad population of patients and in specific subgroups, such as those with type 2 diabetes.

Conclusions: Using anti-PCSK9 antibodies as add-on therapy to other lipid-lowering treatments or as monotherapy for patients unable to tolerate statins may help patients with high cardiovascular risk to achieve their LDL-C goals.

Keywords: LDL cholesterol; PCSK9; alirocumab; evolocumab; hypercholesterolemia; lipoproteins.

© 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Figures

Figure 1
Figure 1
PRISMA flow diagram. PCSK9, proprotein convertase subtilisin/kexin type 9; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐Analyses
Figure 2
Figure 2
LDL‐C goal achievement according to baseline LDL‐C level. HeFH, heterozygous familial hypercholesterolaemia; LDL‐C, LDL cholesterol. Figure includes only studies that reported LDL‐C goal achievement. LDL‐C levels in mg dl−1 are converted to mmol l–1 by dividing by 38.67 97

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