Systematic Review of Published Phase 3 Data on Anti-PCSK9 Monoclonal Antibodies in Patients with Hypercholesterolaemia

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.