JUL 25, 2013
This prospective study determined that the topically applied single-chain antibody fragment ESBA105 can penetrate the anterior chamber of the human eye at therapeutic levels and thus may have an application in reducing post glaucoma surgery fibrosis.
Although not directly related to the glaucomatous eye, this study could have major implications for the delivery of anti-cytokine antibodies, such as transforming growth factor beta, which can be used to decrease postoperative fibrosis in glaucoma surgery and previously has been investigated in a trial utilizing intraocular injection without success. The topical application has the advantage of decreasing the possible complications of intraocular injection, as well as possible systemic effects of the drug.
ESBA105 is an anti-tumor necrosis alpha (TNFα) antibody. The ability to introduce the drug as an eye drop was achieved previously by the authors by introducing the smallest functional unit of the antibody, known as the ScFv, into the eye without using a toxic penetration enhancer, such as sodium caprate. The ScFv contains the full capacity and target specificity of the antibody.
Otherwise healthy patients undergoing cataract surgery or combined cataract surgery and vitrectomy received ESBA105 or placebo. ESBA105 was administered on the day of surgery at one-hour intervals (last dose one hour preoperatively) in 1.6 mg or 3.2 mg doses. Another cohort was randomized to receive either ESBA105 6.4 mg or placebo over four days using four drops per day at four-hour intervals (last dose 12 hours preoperatively).
Use of the drops both four times daily over four days and eight times daily resulted in reliably high ESBA105 concentrations in aqueous humor. Results from the cohorts receiving four and eight hourly drops per one day indicated that dose-dependent intraocular concentrations of ESBA105 were achieved within hours of dosing. After eight times daily dosing, five of six vitreous samples had undetectable ESBA105 levels.
ESBA105 was detected in 17 of 55 preoperative serum samples but no longer detectable in serum one day after surgery. Treatment-emergent adverse events were identical between ESBA105 and placebo groups, with two cases of eye irritation in each group.
The results indicated good penetration and high therapeutic levels of the antibody, with no side effects or any systemic levels of note.