InSite Vision Incorporated announced top-line results from its recently completed phase I/II clinical trial of ISV-303, a topical anti-inflammatory product intended to reduce the pain and inflammation associated with ocular surgery. This randomized four-arm study compared once- and twice-daily doses of ISV-303 versus Xibrom and DuraSite (vehicle), each administered twice-daily. ISV-303 combines a lower dose (0.075%) of the Non-Steroidal Anti-Inflammatory (NSAID) bromfenac (Bromday)/Xibrom (bromfenac ophthalmic solution) 0.09%, marketed by ISTA Pharmaceuticals) with InSite Vision's proprietary DuraSite drug delivery technology.

The phase I/II clinical trial enrolled 169 patients undergoing cataract surgery. The primary endpoint of the study was the absence of cells in the anterior chamber of the eye at day 15 post surgery. Once-daily ISV-303 achieved statistically significant superiority compared to vehicle (53.3% vs. 19.0%, p=0.0016) for the primary endpoint. Further, secondary endpoints such as reduction of flare, pain and discomfort as a result of inflammation, achieved statistically significant superiority at days 8, 15 and 29 as compared with vehicle.

While once-daily ISV-303 achieved a numerically superior difference in the primary endpoint versus twice-daily Xibrom (53.3% vs. 42.2%), the results did not reach statistical significance given the relatively small size of the trial. ISV-303, Xibrom and vehicle were all generally well tolerated and there were no safety concerns or serious adverse events related to any of the agents. InSite Vision intends to present a final analysis of the ISV-303 phase I/II clinical trial in conjunction with a future scientific meeting.

The exploratory phase I/II study was not designed to achieve statistically significant difference between the arms. Nevertheless, the results of this relatively small study comfortably demonstrate the clear efficacy and safety of once-daily ISV-303 over DuraSite in terms of a regulatory pathway, and the promise of a commercially superior once-daily NSAID for post-surgical use in the marketplace. Following final analysis, the company plans to initiate discussions with the US Food and Drug Administration (FDA) on the design of the pivotal phase III programme for once-daily ISV-303. The company also plans to conduct a phase II pharmacokinetic study of once-daily ISV-303 against ISTA Pharmaceutical's currently marketed once-daily NSAID, Bromday.

“It is a delightfully rare situation to experience such stunningly statistically significant results in an exploratory phase I/II study,” said Timothy Ruane, CEO of InSite Vision. “With the efficacy and safety profile established in this study, and potential patent protection extending to 2029, we believe once-daily ISV-303 is very well positioned to compete in the growing $300 million ophthalmic NSAID market in the United States. Importantly, the results of this study further transform InSite Vision into a late-stage company with three phase III candidates that we intend to move toward approval.”

InSite Vision is advancing another product candidate that utilizes a low-concentration of bromfenac enabled by DuraSite. ISV-101, a lower dose of bromfenac in DuraSite, is being developed for the treatment of dry eye disease. On January 11, 2011, InSite Vision announced it had filed an Investigational New Drug (IND) application for ISV-101 with the FDA.

The company is now positioned to initiate a dose-ranging phase I/II clinical trial in 2011 to evaluate the safety and efficacy of ISV-101 when administered to patients suffering from dry eye disease. Patent protection for this drug candidate is also expected to extend into 2029. Preclinical data on the safety of ISV-303 and ISV-101 (bromfenac formulated in DuraSite) on ocular tissues have been accepted for presentation at the 2011 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting being held May 1 - 5, 2011 in Fort Lauderdale, Florida.

Cataract surgery is the most frequently performed ocular surgery in the United States with more than three million procedures annually. Following surgery, anti-inflammatory eye drops are typically prescribed to reduce pain and inflammation and to enhance healing.

Dry eye disease occurs when the surface of the eye becomes compromised for various reasons, frequently involving tear-film changes. While causes of dry eye may vary, it is frequently associated with inflammation of the surface of the eye, the lacrimal gland, and/or the conjunctiva. A potentially chronic condition that can occur at any age, dry eye disease is most prevalent among the elderly. It is estimated to affect at least twenty-five million people in the US alone.

InSite's DuraSite sustained delivery technology is a patented synthetic polymer-based formulation designed to extend the residence time of a drug relative to conventional topical therapies. It enables 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 (azithromycin ophthalmic solution) 1% and Besivance (besifloxacin ophthalmic suspension) 0.6%. InSite vision is also applying DuraSite to multiple other clinical- and preclinical-stage product candidates to create a portfolio of novel ophthalmic products.

InSite Vision is committed to advancing new and superior ophthalmologic products for unmet eye care needs. The company's product portfolio utilizes InSite Vision's proven DuraSite bioadhesive polymer core technology, an innovative platform that extends the duration of drug retention on the surface of the eye, thereby reducing frequency of treatment and improving the efficacy of topically delivered drugs.