Vilobelimab is a chimeric human/mouse monoclonal IgG4 antibody that is a specific inhibitor of the soluble human complement component C5a.
The reduction of C5a plasma concentrations in response to vilobelimab treatment has been evaluated in the PANAMO phase III study. In general, baseline C5a levels were elevated in these patients compared to mean values found in healthy individuals and treatment with vilobelimab reduced the mean baseline C5a levels.
The PK of vilobelimab has not been extensively studied in COVID-19 patients. In the PANAMO phase III trial (n=81 patients), mean vilobelimab plasma trough concentrations on Day 8 ranged from 21,800 to 303,000 ng/mL (147 to 2,040 nM) with a geometric mean of 138,000 ng/mL (929 nM).
Mean (s.d.) volume of distribution after a single 4 mg/kg dose to healthy volunteers was 0.0833 (0.0136) L/kg.
No data are available on the metabolism of vilobelimab in humans. Vilobelimab is a monoclonal antibody and expected to be degraded into small peptides and amino acids via non-specific catabolic pathways in the same manner as endogenous IgG.
In healthy volunteers, target mediated disposition was apparent as mean vilobelimab clearance decreased with dose from 0.06 mL/min/kg after administration of 0.02 mg/kg to 0.02 and 0.01 mL/min/kg after administration of 2 mg/kg and 4 mg/kg, respectively. Mean terminal half-life (t1/2) was found to be 101.3 hours and 94.9 hours after single vilobelimab doses of 2 mg/kg and 4 mg/kg, respectively.
The pharmacokinetics of vilobelimab in paediatric COVID-19 patients has not been studied.
The pharmacokinetics of vilobelimab in patients with renal impairment has not been formally studied. In general, due to its high molecular weight vilobelimab is not expected to undergo significant renal elimination.
The pharmacokinetics of vilobelimab in patients with hepatic impairment has not been studied. Vilobelimab is degraded by widely distributed proteolytic enzymes, not restricted to hepatic tissue, therefore changes in hepatic function are not expected to have any effect on elimination.
There were no adverse effects associated with vilobelimab in conventional repeated dose and pre- and postnatal developmental toxicity studies in Cynomolgus monkeys. Pharmacokinetic data in humans are insufficient to estimate the safety margins provided by these studies.
No specific studies were conducted to evaluate potential effects of vilobelimab on fertility. There were no adverse effects on male or female reproductive parameters or organs in monkeys treated for 13-weeks or 26-weeks, respectively.
Carcinogenesis and mutagenesis studies with vilobelimab have not been conducted.
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