Preclinical Evaluation of NCX 4251, a Novel Steroid Therapy for Blepharitis, Targeted Directly to the Eyelid Margin to Reduce the Potential for IOP Elevations

Abstract

Purpose : NCX 4251 (fluticasone propionate nanocrystal suspension) is a novel experimental therapy being developed for the treatment of acute exacerbations of blepharitis. While blepharitis is a disease of the eyelid margin, currently used steroids are delivered primarily as eye drops, thus failing to reach the target tissue with the majority of the dose and often leading to adverse events (AEs) of intraocular pressure (IOP) elevations. NCX 4251 is being developed to be delivered via an applicator directly to the eyelid margin where the disease originates with the intent of potentially improving efficacy and reducing AEs related to elevated IOP. In this work, the preclinical safety and tolerability were evaluated following 14 day dosing in GLP toxicology study in a Beagle dog model.

Methods : Dogs (5/sex/group) were administered via topical application directly to the margin of upper and lower eyelids of both eyes 0% (vehicle) BID, 0.005% QD, 0.03% QD, 0.1% QD and 0.1% BID NCX 4251 Ophthalmic Suspension for 14 consecutive days. Approximately 16 µL/eye was applied with a sterile swab, corresponding to ocular daily doses of 0, 0.8, 4.8, 16, and 32 µg/eye, respectively. Assessments included clinical observations, body weight, food consumption, intraocular pressure, ophthalmoscopic examination, clinical pathology, toxicokinetics, organ weights, macroscopic observations and microscopic examination of ocular tissues and systemic organs.

Results : Male and female Beagle dogs tolerated all concentrations of NCX 4251 when administered to the eyelids for 14 consecutive days. There were no effects on clinical observations, body weight, food consumption, intraocular pressure, ophthalmoscopic examination, hematology, coagulation, serum clinical chemistry, urinalysis, macroscopic observations and microscopic findings of ocular tissues and systemic organs.

Conclusions : In this preclinical evaluation, safety and tolerability of eyelid administration of a novel fluticasone propionate nanocrystal ophthalmic suspension was conducted in Beagle dogs. NCX 4251 was safe and well tolerated in this preclinical study performed in preparation for initiation of a clinical program in blepharitis patients. Direct application of NCX 4251 to the eyelid margin via an applicator has the potential for improved clinical efficacy and a reduced potential for AEs of IOP elevation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.