In patients with primary hypercholesterolemia, adding REGN727/SAR236553 (SAR236553), a fully human PCSK9 monoclonal antibody, to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol when compared to high-dose atorvastatin alone, according to a study published on Oct. 31 in the New England Journal of Medicine.

The study was a phase 2, multicenter, double-blind, placebo-controlled trial using 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 seven weeks. Results showed the least-squares mean (±SE) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, compared to 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.

Additional Resources Full Study Journal Scan  PCSK9 Inhibition in Patients With Primary Hypercholesterolemia on Atorvastatin Trial Summary

Further, all patients who received SAR236553 attained an LDL cholesterol level of less than 100 mg per deciliter, as compared with 52 percent of those who received 80 mg of atorvastatin plus placebo, and at least 90 percent of the patients who received SAR236553 attained LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter), as compared with 17 percent who received 80 mg of atorvastatin plus placebo.

The authors note that statins are highly efficacious in lowering LCD cholesterol; however, there is a need for more effective therapeutic options for the patients with high initial LDL cholesterol levels and those who have side effects with high-dose statins. As previous studies have shown blocking the interaction between PCSK9 and LDL receptors with the use of SAR236553 lowers LDL cholesterol levels in patients with hypercholesterolemia treated with and without statins, the current study aimed to compare the effects of SAR236553 coadministered with high-dose or low-dose atorvastatin compared to atorvastatin alone.

The authors conclude that "substantially more patients who received SAR236553 than patients who received placebo attained target LCL cholesterol levels of less than 100 mg per deciliter and less than 70 mg per deciliter." However, looking forward, the authors note that larger, long-term studies will be necessary to assess the potential risk of adverse effects of SAR236553.

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