Ophthalmic drug delivery using a multi-layer contact lens design that enables targeting, constant-rate release and failure protection

PROJECT SUMMARY Parent award – Glaucoma is a major problem worldwide, with 60 million people currently affected and 112 million expected by 2040. At present, the primary treatment of glaucoma relies on medication administered as topical eye drops, with prostaglandin analogues, as the first-line therapy, representing 51% of total prescriptions. However, eye drops present significant limitations in bioavailability due to tear drainage, and a poor patient adherence rate of 50% amongst those with a daily drop regimen. Second-line drops require even more frequent dosing per day and hence worse adherence to the therapy is observed. We propose to develop a drug-delivering contact lens (DDCL) with extended wear and sustained drug release of up to 7 days for the treatment of open- angle glaucoma. The goal is to replace topical eye drops as the standard of care for glaucoma. Key advantages of the DDCL will be lower dosing frequency, direct delivery to the corneal surface at a constant rate, high- precision dosing and targeting, all by a cost-competitive lens device. The proposed Phase II work plan will focus on refining prototypes of the DDCL (including drug release, materials, etc.), scaling up the production, and demonstrating feasibility in animal model studies of tolerability, pharmacokinetics and pharmacodynamics. The proposed DDCL will not only resolve all the deficiencies of eye drop administration, but also could set a new standard against other competing technologies of ocular bandages, injectable polymers, surgical implants, etc. in the following categories: (a) The accurate control of drug release rate between first to zero order kinetics throughout the delivery duration, (b) The precise dosing of bioavailable drug amount based on matching rates of drug discharge, tear turnover and corneal adsorption, (c) The lens material innovation required for 7-day wearing comfort, safety, easy of handling (by elderlies), and at a competitive cost. At the end of Phase II, final production- scale prototypes with animal feasibility data (63 rabbits, toxicity/PK/PD) will be ready for subsequent IND- enabling studies and IND filing for study in humans as proposed in an upcoming Phase IIb project. Administrative supplement – This administrative supplement proposes $168,192 of incremental budget costs to complete subaward animal research that was previously planned with a university (Temple), but due to timing, personnel and other constraints has been moved to a CRO (Ora Inc.). The study design remains the same, with the only changes being the subawardee, facility, and budget that will allow for timely completion of the work. Updated IACUC approval and OLAW assurance have already been completed.PROJECT NARRATIVE The parent proposal aims to create a commercially viable contact lens for ocular drug delivery in patients with open angle glaucoma, a disease that affects 2.8 million Americans and eventually leads to blindness. The current treatment standard of topical eye drops has notable limitations such as poor drug absorption (5-10%) and patient compliance (50% or less), while prior Randamp;D attempts of contact lens drug delivery have failed to reach commercialization due to limitations in release duration, release rate and biocompatibility. By solving these issues, our proposed approach should supersede eye drops in drug absorption and compliance, replacing them as the treatment method of choice in the $5 billion glaucoma drug market, and creating a new platform to treat ophthalmic disease, correct vision and perform diagnostic monitoring. This administrative supplement proposes $168,192 of incremental budget costs to complete subaward animal research that was previously planned with a university (Temple), but due to timing, personnel and other constraints has been moved to a CRO (Ora Inc.). The study design remains the same, with the only changes being the subawardee, facility, and budget that will allow for timely completion of the work.