Table 1.

Pharmacological properties of ofatumumab

Pharmacodynamic properties
B cell depletion	In the phase II APLIOS study, B cell count < 10 cells/μL was seen in 84.6% of ofatumumab recipients at day 14 and sustained by > 95% of pts until end of study [13]
	In phase III trials, rapid and sustained reduction in B cell count (using an anti-CD19+ assay) was seen in ofatumumab recipients (and across all pt subgroups); 94% of pts had < 10 cells/µL (LLN 40 cells/µL) at study week 4 and sustained for up to week 120 with continued treatment [6, 9, 10]. B cell count was below LLN in 77.0–78.8% of pts after one dose, in 99.3–99.5% of pts at week 12, and in ≈ 92–97% of pts from week 12–120 [9]
B cell repletion	Median time to B cell recovery (to LLN or baseline) post treatment discontinuation was 24.6 weeks in phase III clinical trials [10]; pharmacokinetic modelling and simulation data for B cell repletion estimated a median of 23–40 weeks [9, 10]. Faster post-treatment B-cell repletion than several other anti-CD20 monoclonal antibodies [28]
Immunogenicity	Incidence of anti-drug antibodies in phase III trials too low (0.2% of pts) for evaluation [9, 10]
Pharmacokinetic properties [9, 10]
Non-linear pharmacokinetics; clearance decreased over time (due to B cell depletion) [10]
Absorbed mainly via the lymphatic system; at steady state, once-monthly SC dosing of ofatumumab 20 mg results in a mean AUCτ of 483 µg·h/mL and a mean Cmax of 1.43 µg/mL
Estimated steady-state volume of distribution was 5.42 L
Metabolised by ubiquitous proteolytic enzymes into small peptides and amino acids
Eliminated by target-mediated route (binds to B cells) and target-independent route (mediated by non-specific endocytosis, then intracellular catabolism); higher baseline B cell count results in more target-mediated elimination, leading to greater clearance, which causes B cell depletion; estimated clearance 0.34 L/day following B cell depletion [9]
Steady-state half-life ≈ 16 days
Drug interactions and effect in pts with abnormal liver or kidney function have not been studied (dose modification not expected [10])

AUC_τ area under the plasma concentration-time curve over the dosing interval, C_max maximum drug concentration, LLN lower limit of normal, pt(s) patient(s), SC subcutaneous