LDL-Lowering Monoclonal Antibody Shines in Early Clinical Trials

Results obtained in three phase 1 trials showed that a monoclonal antibody to the protein proprotein convertase subtilisin/kexin 9 (PCSK9) significantly reduced LDL (low-density lipoprotein) cholesterol levels in healthy volunteers and in subjects with familial or nonfamilial hypercholesterolemia.

PCSK9 is a serine protease, which binds to LDL receptors (LDLR), leading to their accelerated degradation, and to increased LDL cholesterol levels. The pharmaceutical company Regeneron (Tarrytown, NY, USA) is among several that have developed monoclonal antibodies specific for PCSK9 for clinical applications.

A paper published in the March 22, 2012, issue of the New England Journal of Medicine (NEJM) presented results of three clinical trials that were conducted to test the safety and effectiveness of REGN727 in human subjects.

The first set of trials comprised two randomized, single ascending-dose studies of REGN727 administered either intravenously (40 subjects) or subcutaneously (32 subjects), as compared with placebo. These studies were followed by a randomized, placebo-controlled, multiple-dose trial in adults with heterozygous familial hypercholesterolemia who were receiving atorvastatin (21 subjects) and those with nonfamilial hypercholesterolemia who were receiving treatment with atorvastatin (30 subjects). REGN727 doses of 50, 100, or 150 mg were administered subcutaneously on days 1, 29, and 43.

Results revealed that the drug was safe, since that among subjects receiving REGN727, there were no discontinuations because of adverse events. REGN727 significantly lowered LDL cholesterol levels in all the studies with up to a reduction of 60-65% in LDL cholesterol levels.

Regeneron employed their proprietary VelocImmune technology to derive a fully human monoclonal therapeutic antibody, which has shown excellent potential at this early stage of clinical trials.

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