Inspire presents data on denufosol therapy for cystic fibrosis at NACFC conference

Oct 22 2010

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, Inspire'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, Inspire'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.

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

Key denufosol presentations at NACFC include:

• "Denufosol Efficacy in Patients with Minimally Impaired Baseline Lung Function and on Minimal Background Therapy Demonstrates its Potential as Early Intervention for Cystic Fibrosis Lung Disease" - 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.

• "Denufosol Improved Lung Function and was Well Tolerated in Adolescents with Cystic Fibrosis" - This presentation highlights subgroup data from the pre-specified analysis of adolescent CF patients aged 12-18 years old from TIGER-1.
• "Denufosol Regulates Ion Transport, Apical Surface Liquid Height and Cilia Beat Frequency in Primary Human Airway Epithelial Cells" - 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).
• "Denufosol Aerosol Properties, Pharmacokinetics, and Efficacy and Safety Profiles Demonstrate its Potential as Early Disease State Intervention for Cystic Fibrosis Lung Disease" - 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, "Denufosol Efficacy in Patients with Minimally Impaired Baseline Lung Function and on Minimal Background Therapy Demonstrates its Potential as Early Intervention for Cystic Fibrosis Lung Disease" (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, "Emerging Strategies & Clinical Progress in CF Therapeutics." 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>1 (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%>1>1 and 2.2% for percent predicted FEV₁. These improvements exceeded those in the ITT population in which >50% of patients used ≥4 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, "Denufosol Improved Lung Function and was Well Tolerated in Adolescents with Cystic Fibrosis" (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>1 for the adolescent patients treated with denufosol at the Week 24 Endpoint was 112 mL compared to -10 mL for placebo>1 from baseline was -1.1% for denufosol compared with -4.1% for placebo>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>1 of 45 mL (2%,>

The poster, "Denufosol Regulates Ion Transport, Apical Surface Liquid Height and Cilia Beat Frequency in Primary Human Airway Epithelial Cells" (M.S. Cowlen, S.F. Okada, M.J. Stutts, R.C. Boucher), highlights research that further examined denufosol'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, "Denufosol Aerosol Properties, Pharmacokinetics, and Efficacy and Safety Profiles Demonstrate its Potential as Early Disease State Intervention for Cystic Fibrosis Lung Disease" (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 µm, 2.4 µm 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 ≤110% predicted FEV₁>

The poster, "Nonclinical Development of Denufosol, a Novel Ion Channel Regulator and Investigational Early Intervention Therapy for Cystic Fibrosis" (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, "Lung and Plasma Pharmacokinetics of Inhaled Denufosol in Sprague-Dawley Rats" (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, "Chronic Daily Treatment with Denufosol is Not Inflammatory in Respiratory Tract Tissue of Rats and Dogs" (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.

Source: Inspire Pharmaceuticals, Inc.