ISTA Pharmaceuticals announces trial results for topical Xibrom 0.09%

ISTA Pharmaceuticals, Inc. has announced results from the Company's recently completed Phase III clinical program of Xibrom (0.09% bromfenac sodium ophthalmic solution) QD (once-daily).

The program enrolled 282 patients who underwent cataract surgery in two U.S. multi-center, randomized, double-masked, parallel-group, vehicle-controlled studies to evaluate Xibrom 0.09% dosed once daily to vehicle (placebo). The identical trials were performed under a common protocol and designated the East region trial (ER) and the West region trial (WR).

According to a preliminary analysis, integrated results for the two studies demonstrated Xibrom 0.09% QD achieved statistical significance in meeting the primary efficacy endpoint of absence of ocular inflammation 15 days following surgery. In addition, Xibrom 0.09% QD met the secondary efficacy endpoint of elimination of ocular pain one day post surgery.

When considered independently, the WR trial showed statistical significance in both the primary and secondary efficacy endpoints. The ER exhibited strong trends in both the absence of ocular inflammation and pain but did not meet statistical significance for either. The rate of patients who discontinued due to lack of efficacy in the ER was six times greater than the WR trial and a previous clinical trial utilizing the same protocol and concentration. In addition, there was a 20 percentage-point higher placebo effect for the relief of pain in the ER compared with the WR results and with previous trial experience with bromfenac ophthalmic solution. Despite the unexpected results reported for the ER Phase III study, there were strong trends in favor of statistical efficacy.

In addition, both Phase III studies showed highly statistically significant results in the proportion of subjects with no photophobia (light sensitivity) at every study visit post-cataract surgery. This is in concordance with previous clinical trials with Xibrom. The studies also showed no serious ocular or systemic adverse events, and the safety profile is consistent with ISTA's currently marketed Xibrom twice-daily formulation.

ISTA has discussed the data with the FDA and plans to perform a confirmatory Phase III trial that it expects to complete in 2009.

According to the Phase III protocols, patients who were undergoing cataract surgery in one eye were assigned randomly (1:1) to receive either Xibrom once daily or placebo. Dosing began one day before cataract surgery and continued for 14 days following surgery. The proportion of patients experiencing no pain was assessed at Day 1 post surgery, and the proportion of patients with complete absence of ocular inflammation was assessed on Day 15 post surgery. Ocular inflammation was evaluated using a summed ocular inflammation score (SOIS) and was measured by an assessment of immune cells in the anterior chamber of the eye ("cells") and cellular debris ("flare"). The secondary efficacy endpoint was evaluated via a pain score from the Ocular Comfort Grading Assessment recorded in a diary.

Patients also graded their symptoms at each office visit, which included photophobia, the chief symptomatic complaint of cataract surgery.

Xibrom is a topical non-steroidal anti-inflammatory compound for the treatment of ocular inflammation and pain following cataract surgery. Xibrom, under a different trade name but identical formulation, was launched in Japan in 2000 by Senju Pharmaceuticals Co. Ltd. ISTA acquired U.S. marketing rights for Xibrom in 2002 and launched the product in the U.S. in 2005. According to IMS data, Xibrom was the fastest-growing branded ophthalmic product (with sales greater than $10 million) in the nine-month period ended September 2008.