Lampalizumab is an antigen-binding fragment of a humanized monoclonal antibody against complement factor D (CFD), a rate-limiting enzyme in the activation and amplification of the alternative complement pathway (ACP), that is being developed for the treatment of geographic atrophy. Following intravitreal administration in cynomolgus monkeys, lampalizumab achieves rapid equilibration across ocular tissues. Lampalizumab ocular elimination is relatively slow with a τ1/2 of approximately 3 days, while systemic elimination is rapid with a τ1/2 of 0.8 hours. Target-independent linear clearance is predominant in the eye, whereas target-mediated clearance is predominant in the systemic circulation. Systemic CFD synthesis was estimated to be high; however, the amount of CFD entering the eye due to influx from the systemic circulation was small and is thus expected to have an insignificant impact on the clinical dose-regimen decision. Our findings support the clinical use of intravitreal lampalizumab to achieve significant ocular ACP inhibition while maintaining low systemic exposure.
See article at J Pharmacol Exp Ther 2015, 355:288-296.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics