Ocriplasmin has a proteolytic activity against protein components of the vitreous body and the vitreoretinal interface (VRI) (e.g. laminin, fibronectin and collagen) and aims to dissolve the protein matrix responsible for the abnormal vitreomacular adhesion (VMA). The tight binding of the protein components within the macular area of the VRI contribute to vitreomacular traction (VMT), leading to visual impairment and/or macular holes.
Ocriplasmin levels in the vitreous decrease rapidly after intravitreal administration. In a clinical study in patients scheduled for vitrectomy receiving 0.125 mg ocriplasmin (corresponding to a theoretical start concentration of 29 µg/mL vitreous), mean ocriplasmin activity was 9% of theoretical start concentration 2-4 hours after injection and below the lower level of quantification at 7 days.
Because of the small dose administered (0.125 mg), detectable levels of ocriplasmin in systemic circulation are not expected after intravitreal injection.
When administered intravenously, ocriplasmin enters the endogenous protein catabolism pathway through which it is rapidly inactivated via its interactions with protease inhibitor α2-antiplasmin or α2-macroglobulin. The inactive ocriplasmin/α2-antiplasmin complex is cleared from the circulation with a half-life (t1/2) of several hours.
No studies have been conducted to examine the pharmacokinetics of ocriplasmin in patients with renal impairment since the systemic exposure is expected to be very low after intravitreal administration.
No studies have been conducted to examine the pharmacokinetics of ocriplasmin in patients with hepatic impairment since the systemic exposure is expected to be very low after intravitreal administration.
The intravitreal toxicity of ocriplasmin has been evaluated in rabbits, monkeys and minipigs. Ocriplasmin induced an inflammatory response and transient ERG changes in rabbits and monkeys, while no inflammation or ERG changes were observed in minipigs. In rabbits and monkeys, the incidence of vitreous cell infiltrates tended to resolve over time. In monkeys, after administration of 125 µg/eye (68 µg/mL vitreous) the ERG was fully recovered by Day 55. Lens subluxation was observed in the 3 species at ocriplasmin concentrations at or above 41 µg/mL vitreous, a concentration above the intended clinical concentration of 29 µg/mL. This effect appeared to be dose-related and was observed in all animals administered intravitreal ocriplasmin more than once. Pathological changes related to intraocular haemorrhage were observed in rabbits and monkeys. It remains unclear if this haemorrhage is related to the injection procedure itself or administration of ocriplasmin. No systemic toxicity was observed after intravitreal administration of ocriplasmin.
The systemic toxicity of ocriplasmin has been evaluated in both rat and dog. Intravenous administration of 10 mg/kg was generally well tolerated in both rat and dog whether administered as single dose or as repeated dose.
No carcinogenicity, mutagenicity or reproductive and developmental toxicity data are available.
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