InSite Vision Incorporated, a company advancing new ophthalmic products for unmet eye care needs based on its innovative DuraSite platform technologies, has completed patient enrollment in the first phase III clinical trial of BromSite (ISV-303) for the reduction of pain and inflammation after cataract surgery. BromSite combines a low dose (0.075 per cent) of the non-steroidal anti-inflammatory drug (NSAID) bromfenac with InSite Vision’s DuraSite drug delivery technology.

This study enrolled more than 240 patients undergoing cataract surgery in a two-arm trial designed to evaluate the efficacy and safety of BromSite against the DuraSite vehicle alone. At 15 separate sites, patients were randomized and then dosed twice-a-day beginning the day before surgery and continuing the day of surgery and 14 days post-surgery. The primary study endpoint is the reduction of pain and inflammation after surgery. Currently, about 80 patients remain on-study. InSite Vision expects that the phase III BromSite clinical trial will be complete and top-line data available in early 2013.

“We are very pleased with the rapid enrollment of the phase III BromSite study. Begun in August, our team has surpassed expectations for accrual and we now look forward to announcing top-line data for the phase III clinical trial of BromSite early next year,” said Timothy Ruane, chief executive officer of InSite Vision. “We are finalizing our plans for a second phase III clinical study of BromSite and, pending positive results from both trials, are committed to filing a New Drug Application for BromSite in 2013.”

This is the first of two phase III clinical studies in support of BromSite’s regulatory submissions. In the second quarter of 2012, InSite conducted an end-of-phase II meeting with the US Food and Drug Administration (FDA) and two European regulatory meetings, where both BromSite pivotal trials were discussed. InSite is finalizing the design of the second phase III study for BromSite pending full input from the regulatory agencies.

“Cataract surgery is the most frequently performed ocular surgery in the US and we believe there is significant opportunity to improve patient care following these procedures,” said Kamran Hosseini, MD, PhD, vice president and chief medical officer of InSite Vision. “Prior clinical trials of BromSite demonstrated superiority over the then market-leader, with twice the tissue penetration using a lower dose of bromfenac due to its formulation in our proprietary DuraSite vehicle. Better tissue penetration should reduce inflammatory symptoms, which are key to preventing post-surgical side effects, in addition to providing longer lasting pain relief to patients.”

InSite reported results in March 2011, from a phase I/II clinical study of 169 patients undergoing cataract surgery, in which once-daily and twice-daily doses of BromSite were compared against the DuraSite vehicle alone. Once-a-day BromSite was demonstrated to be superior to vehicle (53.3 per cent versus 19.0 per cent, P-value of 0.0016) in reducing pain and inflammation. In a phase II clinical study evaluating pharmacokinetics, BromSite achieved more than twice the eye tissue penetration than Bromday (bromfenac ophthalmic solution) 0.09 per cent marketed by ISTA Pharmaceuticals. Results from the phase II clinical trial comparing BromSite to Bromday were released in October 2011.

Cataract surgery is the most frequently performed ocular surgery in the United States with more than three million procedures annually. Both before and after surgery, anti-inflammatory eye drops are prescribed to reduce pain and inflammation. Anti-inflammatory eye drops are also administered as prophylaxis against cystoid macular edema, or CME. CME is a relatively rare but extremely serious adverse event in ocular surgery that can lead to blindness. Many physicians believe that a higher penetration of bromfenac into the ocular tissues may reduce the risk of CME. InSite intends to do additional clinical studies post-approval in pursuit of adding prevention of CME to the BromSite label.

While eye drops are a proven delivery mechanism for numerous ocular drugs, efficacy of these agents is impeded by tears and blinking, which rinse the drug from the surface of the eye and limit retention and absorption. InSite’s DuraSite and DuraSite 2 platforms are sustained delivery technologies using a synthetic polymer-based formulation designed to extend the residence time of a drug relative to conventional topical therapies. DuraSite and DuraSite 2 enable topical delivery of a solution, gel or suspension and can be customized for delivering a wide variety of potential drug candidates. The DuraSite platform is currently leveraged in two commercial products for the treatment of bacterial eye infections, AzaSite and Besivance. InSite Vision is advancing a portfolio of novel preclinical- to clinical-stage ophthalmic products based on the DuraSite platform and anticipates advancing future ophthalmic product candidates using the DuraSite 2 platform.