Adding SAR236553 to 80 mg of atorvastatin resulted in a significantly greater percent reduction in LDL cholesterol compared to 80 mg of atorvastatin plus placebo (73.2% vs 17.3%, P<0.001).
RCT (n=92)
Double-blind
Yes
Does adding SAR236553 to atorvastatin reduce LDL cholesterol levels in patients with primary hypercholesterolemia?
Adding a PCSK9 monoclonal antibody to atorvastatin significantly reduces LDL cholesterol levels compared to high-dose atorvastatin alone in patients with primary hypercholesterolemia.
Absolute Event Rate: 73.2% vs 17.3%
p-value: p=<0.001
BACKGROUND: Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels. METHODS: We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment. RESULTS: The least-squares mean (±SE) percent reduction from baseline in LDL cholesterol 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. All the patients who received SAR236553, as compared with 52% of those who received 80 mg of atorvastatin plus placebo, attained an LDL cholesterol level of less than 100 mg per deciliter, and at least 90% of the patients who received SAR236553, as compared with 17% who received 80 mg of atorvastatin plus placebo, attained LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter). CONCLUSIONS: In a randomized trial involving patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT01288469.).
Roth et al. (2012) conducted an RCT in Primary hypercholesterolemia (n=92). SAR236553 plus atorvastatin vs. Placebo once every 2 weeks plus atorvastatin 80 mg daily was evaluated on Percent reduction from baseline in LDL cholesterol (p=<0.001). Adding SAR236553 to 80 mg of atorvastatin resulted in a significantly greater percent reduction in LDL cholesterol compared to 80 mg of atorvastatin plus placebo (73.2% vs 17.3%, P<0.001).