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Andres Garcia, Rozemarijn S Verhoeven, Tyler Pegoraro, Jeremy Hansen, Jinny Conley, Rilee Robeson, Brian C Gilger, Tomas Navratil, Benjamin Yerxa; Preclinical Evaluation of ENV905 (Difluprednate) Ophthalmic Implant: A Clinical Candidate for the Treatment of Pain and Inflammation Associated with Ocular Surgery. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5897. doi: https://doi.org/.
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Topical corticosteroids are widely used in the treatment of inflammation and pain following ocular surgery. However, topical therapies possess several shortcomings including frequent dosing and low patient adherence. We evaluated the efficacy, duration of action, and tolerability of ENV905 (difluprednate) Ophthalmic Implant for the treatment of inflammation and pain associated with ocular surgery. ENV905 is a biocompatible polymer drug delivery system designed for administration during ocular surgery, providing therapeutic concentrations of difluprednate over 4 weeks in a tapering manner.
We used PRINT® technology to fabricate solid implants for either subconjunctival (SC) or intracameral (IC) delivery. A post-operative inflammation model was used to evaluate the efficacy and safety of ENV905 in albino rabbits over a period of 4 weeks. Animals (2-4/group) received a 2.7 mm corneal incision and ENV905 or placebo administration on Day 1, and anterior chamber paracentesis via a 30G needle on days 9, 15 and 22; Durezol® QID was used as a positive control. Animals were observed for general tolerability and were examined for ocular inflammation using slit lamp ophthalmoscopy and Hackett-McDonald scoring.
ENV905 was successfully administered via either SC or IC injection using a custom applicator, and no adverse effects were noted during the study. SC implants remained at the injection site, IC implants nestled in the inferior iridocorneal angle following dosing, and no implants were visible upon completion of the study. Suppression of ocular inflammation for ENV905 was marked compared with placebo, and was superior or equivalent to that observed with QID Durezol at all time points throughout the 4 week period.
ENV905 delivered via a single SC or IC administration in rabbits was well tolerated and demonstrated a robust reduction in ocular inflammation over 4 weeks. The results from this study show that ENV905 provides a sustained therapeutic effect following a single dose, thus potentially bypassing the need for topical therapies requiring multiple daily instillations. By resolving low patient compliance and eliminating the peaks and troughs in drug concentration, sustained drug delivery of ocular difluprednate may further improve the overall control of post-operative inflammation and pain.
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