ISTA Pharmaceuticals announces new clinical findings to support Bepreve NDA

Apr 30 2008

ISTA Pharmaceuticals, Inc. has announced positive results from the preliminary analysis of its second and final Bepreve (bepotastine ophthalmic solution) Phase III clinical study.

The U.S. multi-center conjunctival allergen challenge (CAC) study evaluated the onset and duration of effect of two Bepreve concentrations in 130 patients with a history of ocular allergies. Both concentrations demonstrated highly statistically significant reductions in the primary study endpoint of ocular itching. In addition, both concentrations produced highly statistically significant effects on the rapidity of response and in the secondary endpoints measuring additional signs and symptoms of ocular allergy, as well as improvement in total nasal symptoms. There were no serious ocular adverse events reported in patients dosed with Bepreve.

The Phase III study was a multi-center, double-masked, placebo-controlled study. It was designed to evaluate the onset and duration of effect of Bepreve in two concentrations and in two dosing schedules, once-daily and twice-daily. Of the 130 patients enrolled, 117 completed the study. Patients were randomized 1:1:1 to receive one of two concentrations of Bepreve. They were evaluated on 3 separate visits for their response to the dose administered, which would allow for the determination of the time to onset, response at 8 hours and at 16 hours. Both statistical significance and degree of clinical response, were measured. The strongest clinical effect achieved was with twice-daily dosing of either concentration. Further, the higher concentration of Bepreve demonstrated a once-daily clinical effect that was comparable to the published literature for FDA-approved once-daily ophthalmic solutions studied in patients with ocular allergies.

The data announced today mirror the results from the 107-patient, single- center Phase III Bepreve study, announced May 8, 2007, which used the same study design. ISTA currently is analyzing the results of an ocular safety study in approximately 850 patients, with preliminary results anticipated before the end of the second quarter of 2008. Once the Company completes its analysis of the full dataset, ISTA expects to file a New Drug Application (NDA) with the FDA during the second half of 2008. ISTA plans to discuss the study results with the FDA to determine what, if any, additional information would be required in order to obtain approval for both a once-daily and twice- daily form of Bepreve.

Bepreve has three primary mechanisms of action: it is a non-sedating, highly selective antagonist of the histamine 1 (H1) receptor, it has a stabilizing effect on mast cells, and it suppresses the migration of eosinophils into inflamed tissues. The compound's primary mechanisms of action are believed to make it an effective treatment against the signs and symptoms of allergic conjunctivitis.

Bepotastine was approved in Japan for use as a systemic drug in the treatment of allergic rhinitis and urticaria/pruritus in July 2000 and January 2002, respectively, and is marketed by Mitsubishi Tanabe Pharma Corporation (formerly Tanabe Seiyaku Co., Ltd.) under the brand name TALION(R). TALION was co-developed by Tanabe Seiyaku and Ube Industries, Ltd., who discovered bepotastine. In 2001, Tanabe Seiyaku granted Senju Pharmaceutical Co., Ltd., exclusive worldwide rights, with the exception of certain Asian countries, to develop, manufacture, and market bepotastine for ophthalmic use. In 2006, ISTA licensed from Senju the exclusive North American rights to an eye drop formulation of bepotastine for the treatment of allergic conjunctivitis.