ISTA Pharmaceuticals Reports Positive Preliminary Results from its Phase 1/2 Clinical Study of Bepotastine Besilate Nasal Spray for the Treatment of Symptoms Associated with Seasonal Allergic Rhinitis

IRVINE, Calif., Oct. 6 /PRNewswire-FirstCall/ -- ISTA Pharmaceuticals, Inc. (Nasdaq: ISTA), today announced positive preliminary results from a Phase 1/2 clinical study of bepotastine besilate nasal spray conducted in Canada for the treatment of symptoms associated with seasonal allergic rhinitis, the inflammation of the nasal passages caused by allergies. The findings demonstrated two of the three bepotastine besilate concentrations tested were effective in relieving patients' nasal symptoms after exposure to seasonal allergens. The safety data showed the drug to be well-tolerated, with adverse events consistent with those observed with other antihistamine nasal sprays and generally rated as mild. As a result of the positive outcomes, ISTA plans to submit an Investigational New Drug (IND) Application to the U.S. Food and Drug Administration (FDA) and to initiate Phase 2 clinical studies of bepotastine besilate nasal spray before the end of 2010.

Commenting on the results of the study, Timothy R. McNamara, Pharm.D., Vice President of Clinical Research and Medical Affairs of ISTA Pharmaceuticals, said, "During the clinical trials for BEPREVE®, our twice-daily prescription eye drop for ocular itching associated with allergic conjunctivitis, patients noted improvement in nasal symptoms. The Phase 1/2 study data with bepotastine besilate nasal sprays supports our initial findings with the BEPREVE ophthalmic solution on the efficacy of bepotastine for the treatment of nasal symptoms.

"The results of our nasal bepotastine Phase 1/2 clinical study in Canada show a robust patient response to the nasal spray without serious side effects, giving us confidence to move forward into Phase 2 clinical trials.  We plan to file an IND application for bepotastine nasal spray and start a Phase 2 trial in Texas before year-end 2010, using one of the most potent seasonal allergy triggers, Mountain Cedar pollen.  Assuming timely filing of the IND application and timely commencement and completion of the Phase 2 studies, we expect to report preliminary Phase 2 data from the Mountain Cedar pollen study during the first half of 2011."

About the Phase 1/2 Bepotastine Besilate Nasal Spray Clinical Study And Results

The Phase 1/2 study was a double-masked, randomized, placebo-controlled, parallel-group study evaluating the safety and efficacy of three concentrations of bepotastine besilate, dosed twice daily, in an Environmental Exposure Chamber (EEC) treatment model for allergic rhinitis.  Following initial screening, 82 patients (males and females, aged 18 – 65 years) were exposed on multiple occasions in the EEC to a high aerosol concentration of a common seasonal allergen to which they were sensitive. The patients graded their individual symptoms at select time intervals prior to and following a single dose or one week of dosing with bepotastine besilate nasal spray or placebo. In addition, pharmacokinetic (PK) data on the three concentrations of bepotastine besilate nasal spray were assessed based on blood draws from a subset of patients.  Reported allergy symptoms included both nasal symptoms and ocular symptoms. Safety was evaluated based on several variables, including adverse events, physical and nasal examinations, vital signs, electrocardiograms, and the mean grades for questions on a brief satisfaction and tolerability questionnaire completed at the end of the study.

This clinical study showed the highest two concentrations of bepotatine besilate nasal spray tested provided both statistically significant and clinically meaningful improvement compared to placebo in reducing total nasal symptoms. This was true in reports from patients for both instantaneous and reflective experiences of their total nasal symptoms. Statistically significant improvements also were seen for all individual nasal symptoms, with the most rapid improvement seen for drug-related reductions in sneezing and nasal itching.

The PK information collected in the study supported the principle that the systemic bioavailability of bepotastine from the nasal sprays approximated dose proportionality. With regards to safety, the total number of adverse events was similar in all treatment groups, with the most common adverse events reported being bitter taste, headache, nasal pain and discomfort, and nosebleed. These adverse events were generally mild. Additionally, no serious adverse events were observed during the Phase 1/2 study.  

About Allergic Rhinitis

According to the American Academy of Allergy Asthma & Immunology (AAAAI), approximately 60 million Americans are affected by allergic rhinitis, an inflammation of the nasal passages caused by exposure to certain allergens, such as pollen from trees, grass and plants, animal dander, feathers, dust mites and molds. Allergic rhinitis is characterized by a number of symptoms, including sneezing, nasal congestion, nasal itching and runny nose.  The eyes, ears, sinuses, and throat also can be affected. Current treatments for allergic rhinitis include antihistamines, mast cell stabilizers, anti-inflammatories, and steroids.  Based on data from IMS Health in the U.S., approximately 43.3 million prescriptions were filled for nasal allergy treatments in 2009, resulting in sales of approximately $2.2 billion.

About bepotastine besilate

Bepotastine besilate is a non-sedating, highly selective antagonist of the histamine 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 for nasal symptoms associated with allergic rhinitis.

Bepotastine besilate has been approved in Japan for systemic use in the treatment of allergic rhinitis since 2000 and for urticaria/pruritus since 2002.  It is marketed in Japan by Mitsubishi Tanabe Pharma Corporation (formerly Tanabe Seiyaku Co., Ltd.) under the brand name TALION®.  TALION was co-developed by Tanabe Seiyaku and Ube Industries, Ltd., who discovered bepotastine besilate.  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 besilate for ophthalmic use. In 2006, ISTA licensed the exclusive North American ophthalmic rights to bepotastine besilate from Senju. In 2007, ISTA licensed exclusive North American rights to nasal dosage forms of bepotastine besilate from Tanabe Seiyaku and obtained a future right to negotiate for a North American license to oral dosage forms of bepotastine besilate for allergy treatment.

ISTA's eye drop formulation of bepotastine besilate, BEPREVE® (bepotastine besilate ophthalmic solution) 1.5%, was approved by the U.S. Food and Drug Administration (FDA) in September 2009 for the treatment of ocular itching associated with allergic conjunctivitis.  ISTA's nasal spray formulation for allergic rhinitis currently is an investigational drug in clinical studies and has not yet been approved by the FDA.

About ISTA Pharmaceuticals

ISTA Pharmaceuticals, Inc., is the fourth largest and fastest growing branded prescription eye care business in the United States, with an expanding focus on allergy therapeutics. ISTA currently markets four products, including treatments for ocular inflammation and pain post-cataract surgery, glaucoma and ocular itching associated with allergic conjunctivitis. The Company's development pipeline contains additional candidates in various stages of development to treat dry eye, ocular inflammation and pain and nasal allergies. Headquartered in Irvine, California, the Company generated 2009 revenues of $111 million. For additional information about ISTA Pharmaceuticals, please visit the corporate website at http://www.istavision.com.

Forward-looking Statements

Any statements contained in this press release that refer to future events or other non-historical matters are forward-looking statements.  Without limiting the foregoing, but by way of example, statements contained in this press release related to the expected submission of an Investigational New Drug (IND) Application to the U.S. Food and Drug Administration (FDA), plans to initiate Phase 2 clinical studies of bepotastine besilate nasal spray before the end of 2010, and ISTA's intention to complete the Phase 2 studies and report preliminary results during the first half of 2011 are forward-looking statements.  Except as required by law, ISTA disclaims any intent or obligation to update any forward-looking statements.  These forward-looking statements are based on ISTA's expectations as of the date of this press release and are subject to risks and uncertainties that could cause actual results to differ materially.  Important factors that could cause actual results to differ from current expectations include, among others, delays and uncertainties related to the FDA or other regulatory agency approval or actions and such other risks and uncertainties as detailed from time to time in ISTA's public filings with the U.S. Securities and Exchange Commission, including but not limited to ISTA's Annual Report on Form 10-K for the year ended December 31, 2009 and its Quarterly Report on Form 10-Q for the quarter ended June 30, 2010.

SOURCE ISTA Pharmaceuticals, Inc.