Diabetes mellitus (DM) in dogs is characterized by a rapid onset of bilateral cataracts that result in vision loss. Over 400,000 dogs annually develop cataracts that results in vision loss and currently the only medical treatment for these dogs is cataract surgery between $3,500-6,000. We have developed an alternative, nonsurgical medical treatment that is composed of an aldose reductase inhibitor in a topical vehicle that has been trademarked as KinostatTM. In our SBIR Phase I study, we established in a masked, multicenter study composed of 40 dogs with naturally occurring DM that topical KinostatTM significantly reduces both cataract formation and the progression of cataracts in diabetic dogs. This Phase II proposal seeks to conduct studies under IAND 11-785 that are required to obtain FDA approval for KinostatTM to become commercially available. Under FDA guidance, the Phase II studies will include a 12-month masked clinical trial conducted at 5 regional clinics with dogs of various breeds with newly diagnosed DM and no cataracts present. Lens changes will be evaluated at the onset, and at 1, 2, 3, 6, and 12 months. The efficacy of topical KinostatTM will be established by comparing the onset and severity of cataract formation in 125 dogs receiving topical KinostatTM compared to 35 dogs receiving placebo. In addition, a 6-month GLP toxicity test in 48 normal dogs of equal gender will be conducted. Both studies will utilize KinostatTM that has been synthesized, formulated and packaged under cGMP and GLP conditions by the future contract manufacturers. Bioequivalence of the manufactured product to the KinostatTM formulation in Phase I will be conducted prior to the start of the clinical trial. In addition, the manufactured formulation will be characterized for consistency of particle size and delivery amounts as mandated by the FDA. The commercial availability of KinostatTM will provide owners of an estimated 1.2 million companion dogs with DM a less costly, nonsurgical alternative medical treatment for cataracts and reduce the incidence of secondary ophthalmic complications.
This proposal seeks funding to obtain data required by the FDA for approval for marketing KinostatTM, a topical aldose reductase inhibitor formulation, for the prevention of cataracts in the 400,000 diabetic companion and working dogs that annually develop cataracts where vision can only be restored with costly cataract surgery. Once KinostatTM has been successfully established for the prevention of cataracts in diabetic dogs, we will repurpose this drug for humans use as an Orphan Drug for preventing aldose reductase linked cataracts in young children with diabetes. This will alleviate the need for cataract surgery in young children where proper intraocular lens placement and secondary cataracts due to posterior capsule opacification are problematic because their eyes are expected to undergo significant ocular growth after surgery.