Chicago, IL—A fully human monoclonal antibody lowered low-density lipoprotein cholesterol (LDL-C) levels an additional 40%, to 72% in hypercholesterolemic patients already being treated with atorvastatin (Lipitor). The antibody binds to PCSK9 to prevent degradation of LDL receptors, facilitating LDL-C transport from the blood to the liver, thereby decreasing circulating levels of LDL-C, reported lead investigator James McKenney, PharmD, President and Chief Executive Officer, National Clinical Research, Inc, and lead investigator of this multicenter, randomized clinical trial of the monoclonal antibody.
A 150-mg injection of SAR236553/REGN727 every 2 weeks lowered LDL-C by 72.4%, from baseline to 12 weeks, said Dr McKenney. “This new mechanism may be the next big step, if it pans out. The data say that [the antibody] is quite powerful, at least as if not more powerful than the statin. It takes us to another level,” he said.
The trial included 183 patients with LDL-C levels of ≥100 mg/dL who were already receiving treatment with atorvastatin, 10 mg to 40 mg daily for at least 6 weeks. They were randomized to placebo or injections of SAR236553/REGN727 every 2 weeks (50, 100, or 150 mg) or every 4 weeks (200 or 300 mg; Table).
“Two weeks after administration, we saw an immediate reduction in LDL cholesterol reaching 31% to 63%,” said Dr McKenney.
The reductions in LDL-C from baseline to week 12 ranged from 39.6% with 50 mg of SAR236553/REGN727 every 2 weeks to 72.4% with 150 mg every 2 weeks. By comparison, the reduction in LDL-C in the placebo group was 5.1%.
There were favorable changes in apolipoprotein B, triglycerides, highdensity lipoprotein cholesterol (HDLC), non–HDL-C, lipoprotein (a), and apolipoprotein A1 in the groups randomized to SAR236553/REGN727.
All patients assigned to 150 mg twice weekly of SAR236553/REGN727 achieved a final LDL-C <70 mg/dL; their mean baseline LDL-C while receiving atorvastatin was 123.9 mg/dL.
The frequency of treatment-emergent adverse events was similar across all groups—placebo and treatment groups—said Dr McKenney. Six patients randomized to SAR236553/ REGN727 discontinued treatment as a result of treatment-emergent adverse events. One of these patients developed leukocytoclastic vasculitis that resolved after treatment with prednisone.
The results support further evaluation of SAR236553/REGN727 in larger, more diverse patient populations, with different background therapies to fully assess efficacy and safety, said Dr McKenney.
“Maybe we have another era in the treatment of lipid disorders, and more important, in the reduction of heart disease in this country,” he said.
“This is one of the few drug classes for which most people who have looked at the data would bet on making it to approval. For all kinds of reasons, having another major class of LDL-lowering drugs that is as powerful as the statins—or more powerful— is a big plus for patients,” commented Steven Nissen, MD, Chair, Department of Cardiovascular Medicine, Cleveland Clinic, OH.
Further studies of SAR236553/REGN727 may reveal an incremental benefit to driving LDL-C levels lower than those currently obtainable, perhaps as low as 50 mg/dL, Dr Nissen noted.