Efficacy and Safety of Bococizumab (RN316/PF-04950615), a Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, in Hypercholesterolemic Japanese Subjects Receiving a Stable Dose of Atorvastatin or Treatment-Naive - Results From a Randomized, Placebo-Controlled, Dose-Ranging Study.

Background: A Phase 2, dose-ranging study of bococizumab, a monoclonal anti-proprotein convertase subtilisin/kexin type 9 antibody, was conducted in Japanese subjects to assess its efficacy, safety, and tolerability in this population.

Methods and results: Two different hypercholesterolemic study populations were enrolled concurrently: Japanese subjects with uncontrolled low-density lipoprotein cholesterol (LDL-C) despite atorvastatin treatment (LDL-C ≥100 mg/dL; n=121), and Japanese subjects naive to lipid-lowering agents and with LDL-C ≥130 mg/dL (n=97). Subjects within each study population were randomized to bococizumab 50, 100, or 150 mg, or placebo, q14D for 16 weeks; an open-label ezetimibe 10 mg daily arm was also included for the atorvastatin-treated population. Significant, dose-dependent reductions in fasting LDL-C levels were observed in all bococizumab arms of both study populations at Weeks 12 and 16 (adjusted mean percent changes from baseline: 54.1-76.7% for atorvastatin-treated subjects and 47.7-66.8% for treatment-naive subjects; P<0.001 vs. placebo for all). Bococizumab also caused dose-dependent changes in other lipid parameters in both study populations at Weeks 12 and 16. No serious adverse events (AEs) related to bococizumab treatment occurred and all treatment-emergent AEs were mild or moderate in severity. No dose-dependent relationship between bococizumab treatment and development of anti-drug antibodies was observed.

Conclusions: Bococizumab was well tolerated and significantly reduced fasting LDL-C in atorvastatin-treated and treatment-naive hypercholesterolemic Japanese subjects. (Clinicaltrials.gov identifier: NCT02055976.).