ISTA Pharmaceuticals, Inc. announced positive, topline results from its phase II dose-ranging, environmental clinical trial of bepotastine besilate nasal spray for the treatment of symptoms associated with seasonal allergic rhinitis, the inflammation of the nasal passages caused by allergies. According to the trial findings, each of three concentrations of bepotastine besilate nasal spray showed statistically significant improvements compared to placebo in patients' nasal symptoms following exposure to Mountain Cedar pollen during the peak season for this allergen.

These improvements were seen on day one of therapy and were sustained through the two-week treatment period. Further, safety data demonstrated bepotastine besilate was well-tolerated as a nasal spray, with an adverse event profile similar to placebo and consistent with those observed with bepotastine besilate dosed as a nasal spray in prior clinical trials and with other antihistamine nasal sprays.

“One of the most potent seasonal allergy triggers in the United States, Mountain Cedar pollen produces a very strong allergic reaction in sensitive patients and is an excellent allergen to assess the activity of bepotastine besilate as a nasal spray,” commented Timothy R McNamara, Pharm.D, vice president of Clinical Research and Medical Affairs of ISTA Pharmaceuticals. “We are very pleased that the first US environmental clinical trial conducted by ISTA showed great promise for the use of bepotastine besilate for allergic rhinitis. Importantly, the phase II protocol for this study is substantially similar to those we would anticipate for the design of a pivotal programme.”

Dr McNamara continued, “A next step in the development plan for this drug candidate is to explore clinical study designs for a bepotastine besilate/steroid combination nasal spray and, after completing discussions with the FDA, we plan to initiate a phase II study in Mountain Cedar pollen with our bepotastine besilate/steroid combination nasal spray before the end of 2011. This programme represents an exciting potential expansion of our prescription allergy product line, currently focused on Bepreve (bepotastine besilate ophthalmic solution) 1.5% for the treatment of ocular itching associated with allergic conjunctivitis.”

The phase II trial was a randomized, multi-centre, double-masked, placebo-controlled, dose-ranging, parallel-group environmental trial to evaluate the safety and efficacy of bepotastine besilate, dosed twice daily, in patients presenting with allergic rhinitis caused by Mountain Cedar pollen.

Following initial screening for evidence of Mountain Cedar pollen allergy, approximately 600 patients in Texas, aged 12 years and older, were treated twice per day with one of three concentrations of bepotastine besilate nasal spray or placebo for two weeks. Patients graded both individual nasal and ocular symptoms on a daily basis.

Safety was evaluated based on several variables, including adverse events, physical and nasal examinations, vital signs and the mean grades for responses to questions in the validated Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) completed at the beginning and end of the trial. Pharmacokinetic (PK) data on the three concentrations of bepotastine besilate nasal spray were assessed based on blood draws, and electrocardiograms were additionally collected at pre-dose and post-dose from a subset of patients.

The clinical trial showed all three concentrations of bepotastine besilate nasal spray provided statistically significant improvement compared to placebo in reducing total nasal symptoms. Statistically significant improvements also were seen for all three concentrations compared to placebo in terms of total ocular symptoms. All domains in the RQLQ also showed a statistically significant improvement in quality of life with two of the three bepotastine besilate nasal spray concentrations.

The PK information collected in the Mountain Cedar trial supported the principle that the systemic bioavailability of bepotastine from nasal sprays approximated dose proportionality. In regard to safety, the total number of adverse events was similar in all treatment groups, with the most common adverse events reported being taste, headache, nasal pain and discomfort, and nosebleed. These adverse events were generally mild. Additionally, no serious drug-related adverse events were observed during the phase II trial.

ISTA expects to report comprehensive data from the phase II trial at an appropriate, peer-reviewed forum in the near future.

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, grasses and plants, animal dander, feathers, dust mites, and moulds. 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 US, approximately 46.3 million prescriptions were filled for nasal allergy treatments in 2010, resulting in sales of approximately $2.5 billion.

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 suggest that it is a potentially effective treatment for nasal symptoms associated with seasonal 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 US Food and Drug Administration (FDA) in September 2009 for the treatment of ocular itching associated with allergic conjunctivitis. ISTA's nasal spray formulations for treatment of nasal symptoms of seasonal allergic rhinitis currently are investigational drugs in clinical studies and have not yet been approved by the FDA.

ISTA Pharmaceuticals, Inc. is a fast growing and the fourth largest branded prescription eye care business in the United States, with an expanding focus on allergy therapeutics.