PCSK9 shows benefit in cholesterol lowering

Despite the potency of high dose statins, many patients fail to reach targets for low-density lipoprotein (LDL) cholesterol reduction. Whilst the addition of a second agent such as niacin or ezetemibe results in an additional 10–20% reduction in cholesterol, there remains an unmet need for more potent therapies. Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing their degradation and reducing the rate at which LDL cholesterol is removed from the circulation. The injectable fully human monoclonal antibody SAR236553 binds PCSK9, resulting in increases in LDL receptor recycling and reductions in LDL cholesterol. In this phase 2, multicenter, double-blind, placebo-controlled trial 92 patients who had LDL cholesterol levels of 2.6 mmol/l or higher despite statin therapy were randomised to 8 weeks treatment with atorvastatin 80 mg plus SAR236553 fortnightly, atorvastatin 10 mg plus SAR236553, or atorvastatin 80 mg plus placebo injections. The primary end-point was the change in LDL at 8 weeks. The least-squares mean (±SE) percent reduction in LDL was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo (p<0.001) and 66.2±3.5 with 10 mg of atorvastatin plus SAR236553 (p<0.001). All the patients who received SAR236553, as compared with 52% of those who received …