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Data Presentations at North American Cystic Fibrosis Conference Highlight Denufosola?s Novel Mechanism of Action

^{Published on 2010-10-21 04:05:38 - Market Wire}
 

DURHAM, N.C.--([ BUSINESS WIRE ])--Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today that data will be presented on denufosol tetrasodium, an investigational therapy for cystic fibrosis (CF), during oral and poster presentations at the 24th Annual North American Cystic Fibrosis Conference (NACFC) October 21-23, 2010 in Baltimore, Maryland.

"Lung and Plasma Pharmacokinetics of Inhaled Denufosol in Sprague-Dawley Rats"

The presentations are based on clinical and nonclinical research conducted with denufosol. The data from TIGER-1, Inspirea™s first Phase 3 clinical trial with denufosol, a novel inhaled ion channel regulator, suggest that denufosol has potential to benefit adolescent patients and those on minimal concomitant therapies. Additionally, Inspirea™s research suggests that denufosol inhibits sodium absorption, stimulates chloride secretion and has the potential to target the small airways of the lungs where CF lung disease begins.

aWe are pleased to share this information from the denufosol development program,a said Charles A. Johnson, M.D., Executive Vice President, Research and Development and Chief Medical Officer. aWe are very excited about denufosola™s potential to affect the primary pathophysiologic defect in CF with a novel mechanism of action that potentially corrects ion transport in patients.a

Key denufosol presentations at NACFC include:

• aDenufosol Efficacy in Patients with Minimally Impaired Baseline Lung Function and on Minimal Background Therapy Demonstrates its Potential as Early Intervention for Cystic Fibrosis Lung Diseasea - This presentation highlights a post-hoc analysis of subgroup data from TIGER-1 patients who were on limited background pharmacotherapies for their lung disease at baseline.

• aDenufosol Improved Lung Function and was Well Tolerated in Adolescents with Cystic Fibrosisa - This presentation highlights subgroup data from the pre-specified analysis of adolescent CF patients aged 12-18 years old from TIGER-1.
• aDenufosol Regulates Ion Transport, Apical Surface Liquid Height and Cilia Beat Frequency in Primary Human Airway Epithelial Cellsa - This presentation highlights new nonclinical research related to the mechanism of action of denufosol focusing on the ability of denufosol to inhibit sodium absorption via the epithelial sodium channel (ENaC).
• aDenufosol Aerosol Properties, Pharmacokinetics, and Efficacy and Safety Profiles Demonstrate its Potential as Early Disease State Intervention for Cystic Fibrosis Lung Diseasea- This presentation highlights nonclinical and clinical data focusing on the aerosol and pharmacokinetic properties of denufosol and how they potentially relate to the safety and efficacy of denufosol.

Summary of Data in NACFC 2010 Denufosol Presentations

The oral presentation, aDenufosol Efficacy in Patients with Minimally Impaired Baseline Lung Function and on Minimal Background Therapy Demonstrates its Potential as Early Intervention for Cystic Fibrosis Lung Diseasea (F. Accurso, W. Tian, A. Schaberg, T. Navratil, M. Howenstine, T. Liou, F. Ratjen), is being presented on Thursday, October 21, 2010 at 11:05 am ET during the session, aEmerging Strategies & Clinical Progress in CF Therapeutics.a The presentation highlights a post-hoc analysis of subgroup data from patients in the TIGER-1 trial who were taking zero to two classes of concomitant medications for CF lung disease at baseline (n=71, intent-to-treat, or ITT=352). These patients had baseline percent predicted FEV₁ (Forced Expiratory Volume in One Second) of 93% in the denufosol group and 91% in the placebo group. During double-blind treatment, FEV₁ improved with denufosol over placebo by 5.7% (p=0.028) or 100 mL (p=0.059) with a net improvement of 6.4% over placebo in percent predicted FEV₁ (p=0.011). Patients on 48 weeks of denufosol improved versus baseline by 12% or 193 mL for FEV₁ and 2.2% for percent predicted FEV₁. These improvements exceeded those in the ITT population in which >50% of patients used a4 pharmacotherapies. Denufosol was well tolerated with a safety profile comparable to that of placebo.

The Company is also presenting six additional poster presentations at NACFC. The poster presentation entitled, aDenufosol Improved Lung Function and was Well Tolerated in Adolescents with Cystic Fibrosisa (R.B. Moss, A. Schaberg, W. Tian, X. Xue, B. Ramsey, F. Accurso), highlights subgroup data from the pre-specified analysis of adolescent CF patients aged 12-18 years old (n=123) from TIGER-1. In this trial, the change from baseline in FEV₁ for the adolescent patients treated with denufosol at the Week 24 Endpoint was 112 mL compared to -10 mL for placebo (p=0.013). Change in percent predicted FEV₁ from baseline was -1.1% for denufosol compared with -4.1% for placebo (p=0.055). The change from baseline for FEF_25%-75% (Forced Expiratory Flow), a measure of small airways function, for the adolescent patients treated with denufosol at the Week 24 Endpoint was 115 mL/sec. compared to -112 mL/sec. for placebo (p=0.036). These results compared favorably to the ITT population (n=352), in which denufosol treatment led to a change from baseline in FEV₁ of 45 mL (2%, p=0.047). Denufosol was well tolerated in adolescent patients with an adverse event profile comparable to that of placebo.

The poster, aDenufosol Regulates Ion Transport, Apical Surface Liquid Height and Cilia Beat Frequency in Primary Human Airway Epithelial Cellsa (M.S. Cowlen, S.F. Okada, M.J. Stutts, R.C. Boucher), highlights research that further examined denufosola™s mechanism of action by investigating the effects of denufosol on sodium absorption through ENaC, chloride secretion through the calcium-activated chloride channel (CaCC), airway surface liquid height, and cilia beat frequency in well-differentiated primary human airway epithelial cells isolated from normal and CF respiratory tract tissue.

The poster, aDenufosol Aerosol Properties, Pharmacokinetics, and Efficacy and Safety Profiles Demonstrate its Potential as Early Disease State Intervention for Cystic Fibrosis Lung Diseasea (F. Ratjen, T. Navratil, C. Evans, A. Schaberg, T. Durham, C. Ren, R. Moss, F. Accurso), reviews nonclinical and clinical data from the denufosol program. Denufosol had a small median droplet size (3.4 to 3.8 m, 2.4 m mass median aerodynamic diameter [MMAD]) suitable for reaching small airways. Following inhalation in the TIGER-1 trial, systemic exposure to denufosol was low to none with no evidence of accumulation with chronic dosing. Denufosol was significantly more effective than placebo in improving FEF_25%-75% in patients with a110% predicted FEV₁ (p=0.025). Consistent with the demonstrated lack of systemic exposure after acute or chronic administration, the adverse event profile of denufosol was comparable to that of placebo. No evidence of systemic effects including no changes in liver enzymes, blood biochemistry or differential blood cell counts was observed.

The poster, aNonclinical Development of Denufosol, a Novel Ion Channel Regulator and Investigational Early Intervention Therapy for Cystic Fibrosisa (M.S. Cowlen), summarizes the nonclinical safety studies conducted with denufosol, which are required by international regulatory agencies. In these studies, denufosol was nongenotoxic, noncarcinogenic and induced no observable clinically relevant pulmonary or systemic adverse effects.

The poster, aLung and Plasma Pharmacokinetics of Inhaled Denufosol in Sprague-Dawley Ratsa (R.S. Verhoeven, M.S. Cowlen), characterizes the pharmacokinetic profile of denufosol in the lung and plasma of rats. In the study, denufosol was rapidly eliminated from the circulation with no sustainable systemic exposure and did not accumulate in the lung during chronic inhalation in rats.

The poster, aChronic Daily Treatment with Denufosol is Not Inflammatory in Respiratory Tract Tissue of Rats and Dogsa (R.S. Verhoeven, A-J Lambert, M.S. Cowlen), showed that in the required one-year and two-year nonclinical studies, denufosol did not increase background levels of pulmonary inflammation after chronic inhalation.

These presentations will be available on Inspirea™s website, [ www.inspirepharm.com ], following the conference.

About Denufosol Tetrasodium

Denufosol is a novel ion channel regulator targeted as an early disease state intervention that potentially corrects ion transport in patients independent of the class of CFTR defect. Denufosol is designed to enhance airway hydration and mucociliary clearance by increasing chloride secretion, inhibiting sodium absorption and increasing ciliary beat frequency. These integrated pharmacological actions and the potential to reach the small airways are key to maintaining lung function and potentially delaying the progression of lung disease.

About the Denufosol Tetrasodium Clinical Program

TIGER-1, the first Phase 3 trial with denufosol for the treatment of CF, included a 24-week placebo-controlled portion, followed by a 24-week open-label safety extension. The placebo-controlled portion was a double-blind, randomized trial comparing 60 mg of denufosol to placebo, administered three times daily by jet nebulizer, in 352 patients with mild cystic fibrosis lung disease (baseline FEV₁ a 75% of predicted normal).

Inspire is currently conducting TIGER-2, its second Phase 3 clinical trial with denufosol, and expects top-line results from this trial in the first quarter of 2011. Inspire is targeting a potential U.S. commercial launch for denufosol in the 2012 timeframe assuming the results of TIGER-2 are positive, that Inspire subsequently files a New Drug Application (NDA) for denufosol with the FDA in the second half of 2011 and that the FDA approves such NDA under a priority review timeline.

Inspire is conducting additional clinical trials in connection with its evolving denufosol franchise development plans and activities. Inspire is conducting DEFY (Denufosol Efficacy Over Four Years), a denufosol open-label clinical trial open to eligible patients that complete the year-long TIGER-2 trial. This three year trial will evaluate the potential disease-modifying impact of denufosol on rate of lung function decline. In August 2010, Inspire also initiated REACH (Researching an Early Approach to Cystic Fibrosis Health), a small safety and tolerability clinical trial of denufosol in CF patients ages 2 - 4 years old.

About Inspire

Inspire is a biopharmaceutical company focused on researching, developing and commercializing prescription pharmaceutical products for ophthalmic and pulmonary diseases. Inspire's goal is to build and commercialize a sustainable portfolio of innovative new products based on its technical, scientific and commercial expertise. Inspire's clinical pipeline includes denufosol tetrasodium for cystic fibrosis in Phase 3 development and AZASITE^® (azithromycin ophthalmic solution) 1% for blepharitis in Phase 2 development. Inspire receives revenues related to the promotion of AZASITE for bacterial conjunctivitis, the co-promotion of ELESTAT^® (epinastine HCl ophthalmic solution) 0.05% for allergic conjunctivitis and royalties based on net sales of RESTASIS^® (cyclosporine ophthalmic emulsion) 0.05% for dry eye. For more information, visit [ www.inspirepharm.com ].

Forward-Looking Statements

The forward-looking statements in this news release relating to management's expectations and beliefs are based on preliminary information and management assumptions. Specifically, no assurances can be made with respect to: denufosol's potential to benefit adolescent patients; denufosol's potential to benefit those patients on minimal concomitant therapies; denufosol's potential as an early disease state intervention that may delay lung disease progression; denufosol's ability to target the small airways of the lungs; denufosol's ability to elicit improvements in CF patients on minimal concomitant therapies; denufosol's ability to increase chloride secretion, inhibit sodium absorption and normalize airway surface liquid depth in primary epithelial cell cultures from CF patients; denufosola™s ability to affect the primary pathophysiologic defect in CF; denufosola™s ability to correct ion transport in CF patients independent of the class of CFTR defect; the timing and outcome of TIGER-2 results in the first quarter of 2011, or otherwise; the ability to undertake, or the timing or outcome of, a U.S. commercial launch of denufosol in 2012, or otherwise; whether or not the results of TIGER-2 will be positive; that Inspire will file a New Drug Application (NDA) for denufosol with the FDA in the second half of 2011; that the FDA will review any denufosol NDA under a priority review timeline; that the FDA will approve denufosol, even if a priority review is undertaken; the timing and outcome of the DEFY open-label clinical trial or the REACH clinical trial; and that Inspire could build and commercialize a sustainable portfolio of innovative new products based on its technical, scientific and commercial expertise. Such forward-looking statements are subject to a wide range of risks and uncertainties that could cause results to differ in material respects, including those relating to product development, revenue, expense and earnings expectations, the timing of a launch of a generic form of ELESTAT, intellectual property rights, competitive products, results and timing of clinical trials, success of marketing efforts, the need for additional research and testing, delays in manufacturing, funding, and the timing and content of decisions made by regulatory authorities, including the U.S. Food and Drug Administration. Further information regarding factors that could affect Inspire's results is included in Inspire's filings with the SEC. Inspire undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances after the date hereof.