Ocular Insert for Non-Invasive Sustained Drug Delivery for the Treatment of Glauc

DESCRIPTION (provided by applicant): The polymer platform technology and the device design developed to date offer the long- term objective of a line of products that can be worn under the eyelid for a day or for months, and useful for a number of ocular conditions that would benefit from a more sustained, controlled and inherently compliant treatment than is available today via the use of eye drops. We have focused through Phase I and Phase II grant award periods on one specific product - a topical ophthalmic drug delivery device (TODDD ) delivering timolol, to treat glaucoma. Timolol is one of the most commonly used glaucoma drugs and is not patent protected. It has a long history of successfully lowering intraocular pressure (IOP), but has some significant ocular and systemic side effects when delivered in drop form. When delivered by TODDD, it should eliminate the incidence and severity of those side effects by continuously delivering a very low, preservative-free dose to the patient and virtually eliminating systemic absorption, as shown in the Phase II animal study. Of great importance to the mission of NEI of preventing vision loss from glaucoma, is that the product will address the 24-59% non-compliance rate among glaucoma patients using drops. This major clinical disadvantage is due mainly to difficult instillation, forgetfulness and undesirable side effects. In this proposed Phase II Renewal project, the goal is to show that the product can be safely and comfortably worn for 90+ days and deliver drug in humans, while addressing issues related to Federal regulatory approval processes. The specific aims of the project encompass the scientific and clinical regulatory requirements attendant to this goal, as well as executive management of the commercialization process. Work will continue on TODDD with timolol, along several scientifically driven regulatory fronts. These aims include design and mold optimization; manufacturing process scale-up, semi- automation and validation; analytical assay testing; sterilization process and testing; clinical product build; and design and conduct of a human design validation study, with one or two drug treatment arms. Our commercialization plan indicates a high degree of commercial potential, as it reflects specific input generated by the interest to date of potential investors and large ophthalmic companies. For example, our focus on a small human feasibility study, with at least one drug arm, is a direct result of this input. Our collaboration with the Massachusetts Medical Device Development (M2D2) Center at U. Mass. and its mission and coordination of resources also offer high potential of success. PUBLIC HEALTH RELEVANCE: Glaucoma is a major ocular disease that severely impacts millions of people. Most are over fifty-five years of age and many have difficulty with instilling drops and suffer from poor compliance with a drops-based therapy. The TODDD product provides a more efficient, convenient and consistent means of drug delivery to the surface of the eye, and reduces the incidence and severity of side effects by delivering a lower, preservative-free dose to the patient and virtually eliminating systemic absorption. It will also reduce the current 24-59% level of non-compliance by remaining in the eye between physician visits (1).