Promising phase 1 results for monoclonal antibody to PCSK9
MedWire News: A monoclonal antibody to proprotein convertase subtilisin/kexin 9 (PCSK9) significantly reduces low-density lipoprotein (LDL) cholesterol levels in healthy volunteers and in individuals with familial or nonfamilial hypercholesterolemia, show results of three phase 1 trials.
The reduction in LDL cholesterol levels was also observed in individuals who were concomitantly taking atorvastatin, notes the team.
"Our results confirm a role for PCSK9 in the regulation of LDL cholesterol levels," say Evan Stein (Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio, USA) and co-investigators.
Writing in The New England Journal of Medicine, Stein and team report the results of three separate studies of REGN727 - a monoclonal antibody that is highly specific for human PCSK9 and blocks its interaction with the LDL receptor.
Two of the studies were randomized single-dose studies of REGN727 administered either intravenously (n=40) or subcutaneously (n=32) in healthy volunteers with serum LDL cholesterol levels above 100 mg/dL (2.59 mmol/L), compared with placebo.
Individuals in the intravenous group were randomly assigned to receive 1, 3, 6, or 12 mg REGN727, while those in the subcutaneous group were assigned to receive 50, 100, 150, or 250 mg REGN727.
The researchers report that individuals receiving a single dose of intravenous or subcutaneous REGN727 had a mean reduction in LDL cholesterol of up to 65% from baseline, as compared with placebo, at the end of the study period (day 106).
The third study was a multiple-dose study in which REGN727 was administered subcutaneously to three cohorts of participants. The first cohort included 21 adults with heterozygous familial hypercholesterolemia and the second included 30 adults with nonfamilial hypercholesterolemia. All of these participants were receiving atorvastatin therapy and had an LDL cholesterol level of more than 100 mg/dL at baseline.
The third cohort consisted of 10 individuals with nonfamilial hypercholesterolemia who were being treated with a modified diet only and had an LDL cholesterol level of more than 130 mg/dL (3.36 mmol/L) at baseline.
All participants in the multiple-dose study were randomly assigned to receive subcutaneous REGN727 50, 100, or 150 mg or placebo administered on days 1, 29, and 43.
The researchers found that REGN727 50, 100, and 150 mg reduced LDL cholesterol levels from baseline by 39.2%, 53.7%, and 61.0%, respectively, compared with placebo at the end of the study period (day 148).
None of the participants receiving REGN727 discontinued treatment because of adverse events.
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By Nikki Withers