Pharmacokinetics and pharmacodynamics of bococizumab, a monoclonal antibody to PCSK9, after single subcutaneous injection at three sites [NCT 02043301].

Aim: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (NCT02043301).

Methods: Seventy-five adults with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and not on background lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm. Blood samples for bococizumab and lipids were collected for 12 weeks postdose.

Results: Plasma bococizumab concentration-time profiles and PK parameters were generally similar across injection sites. Mean maximum observed concentration (C ) ranged from 8.14 to 11.9 μg/mL, and area under the concentration-time curve (AUC ) ranged from 160.3 to 198.9 µg∙day/mL. The median time to C (T ) ranged from 4.25 to 6.93 days. Similar LDL-C concentration-time profiles were observed across injection sites, with mean (% coefficient of variation) maximum reductions in LDL-C of -57.5% (15.8), -57.0% (25.9), and -55.0% (24.1) for the abdomen, thigh, and upper arm, respectively. Adverse events (AEs) were mostly mild and generally similar across injection sites. Commonly reported AEs were upper respiratory tract infection (9.3%), headache (6.7%), and injection site reaction (6.7%). One serious AE was reported (ischemic colitis), which was not considered related to study drug.

Conclusions: Similar PK profiles and robust LDL-C reductions were observed following a single 150-mg s.c. injection of bococizumab administered to the abdomen, thigh, or upper arm in untreated subjects with LDL-C ≥130 mg/dL. Bococizumab was generally well tolerated following a single 150-mg s.c. administration in this subject population.