Effects of 12weeks of treatment with intravenously administered bococizumab, a humanized monoclonal antibody blocking proprotein convertase subtilisin/kexin type 9, in hypercholesterolemic subjects on high-dose statin

AimsTwo multiple-dose phase II studies were conducted in subjects with primary hypercholesterolemia to evaluate the LDL-C lowering efficacy, safety, and tolerability of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. MethodsThe results from the two phase II, double-blinded, randomized, placebo-controlled, multicenter studies conducted in the USA and Canada were combined. In Study 1, 90 subjects with LDL-C 100mg/dL received intravenous (IV) placebo or bococizumab 0.25, 1, 3, or 6mg/kg. In Study 2, 45 subjects with LDL-C 80mg/dL received IV placebo or bococizumab 1 or 3mg/kg. Subjects were treated every 4weeks for 12weeks. Dosing was interrupted if LDL-C dipped to 25mg/dL and resumed if LDL-C returned to 40mg/dL. The primary endpoint was percent LDL-C reduction from baseline at Week 12. ResultsAt Week 12, the reductions from baseline in LDL-C vs placebo in the bococizumab 0.25, 1, 3, and 6mg/kg groups were 9.3%, 10.2%, 41.6%, and 52.0%, respectively (P<.001 vs placebo for all). LDL-C reductions were greater (69.9%) in subjects who received all three doses of bococizumab 6mg/kg (P<.001 vs placebo). Pharmacogenomic analysis revealed that 15% of hyperlipidemic subjects carried polymorphisms associated with familial hypercholesterolemia, with maximal LDL-C reductions being similar between carriers and noncarriers. Adverse events were mild, unrelated to bococizumab, and resolved by Week 12. ConclusionsThese studies demonstrated that bococizumab safely and effectively lowered LDL-C in hypercholesterolemic subjects on high doses of statin.