WEDNESDAY, March 21 (HealthDay News) -- Administration of REGN727, a monoclonal antibody to proprotein convertase subtilisin/kexin 9 (PCSK9), significantly reduces low-density lipoprotein (LDL) cholesterol levels, according to the results of three phase 1 studies published in the March 22 issue of the New England Journal of Medicine.
Evan A. Stein, M.D., Ph.D., from the Metabolic and Atherosclerosis Research Center in Cincinnati, and colleagues conducted three phase 1 randomized trials. Two were single ascending-dose studies of REGN727, administered intravenously (to 40 individuals) or subcutaneously (to 32 individuals), compared with placebo. The third trial was conducted in 21 adults with heterozygous familial hypercholesterolemia who were receiving atorvastatin, and in individuals with non-familial hypercholesterolemia who were receiving treatment with atorvastatin (30 participants; baseline LDL cholesterol, >100 mg/dL) or modified diet alone (10 participants; baseline LDL cholesterol, >130 mg/dL). Subcutaneous administration of REGN727 at doses of 50, 100, or 150 mg was performed on days one, 29, and 43.
The researchers found that, in all studies, REGN727 significantly lowered LDL cholesterol levels, with no discontinuation due to adverse events. In the multiple-dose study, there was a significant reduction in the LDL cholesterol levels in the combined atorvastatin-treated populations, to 77.5 mg/dL, 61.3 mg/dL, and 53.8 mg/dL for REGN727 doses of 50, 100, and 150 mg, respectively. Compared with placebo, the difference in the change from baseline was −39.2, −53.7, and −61.0 percentage points, respectively.
"In three phase 1 trials, a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels in healthy volunteers and in subjects with familial or non-familial hypercholesterolemia," the authors write.
The study was funded by Regeneron Pharmaceuticals and Sanofi, who together are developing REGN727; several authors disclosed financial relationships with Regeneron, including employment and patent applications.
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