Gilead Announces Detailed Results of Phase III Study of Aztreonam Lysine for Inhalation in Patients With Cystic Fibrosis

Gilead Sciences, Inc. (Nasdaq:GILD) today announced detailed results of its Phase III AIR-CF1 (CP-AI-007) study of aztreonam lysine for inhalation, an investigational therapy in development for the treatment of people with cystic fibrosis (CF) who have pulmonary Pseudomonas aeruginosa (P. aeruginosa). In this study, a 28-day treatment course of aztreonam lysine improved respiratory symptoms as assessed by the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a patient-reported outcome (PRO) tool. Aztreonam lysine also improved pulmonary function in this study, as measured by relative improvement of forced expiratory volume in one second (FEV1), a standard measure of lung function. The data were presented by George Z. Retsch-Bogart, MD, Associate Professor of Pediatrics at the University of North Carolina, Chapel Hill, at the 21st Annual North American Cystic Fibrosis Conference (NACFC) in Anaheim, California. Topline results from this study were previously announced on May 29, 2007. "Cystic fibrosis causes a type of chronic lung disease that is characterized by recurring or persistent bacterial infection, which leads to gradually declining lung function, exercise capacity and quality of life,” said Dr. Retsch-Bogart. "These study results are particularly encouraging, given that patients experienced meaningful improvements as measured by both patient-reported respiratory symptoms and also traditional pulmonary function endpoints such as FEV1.” AIR-CF1 was a randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of a 28-day treatment course of aztreonam lysine in people with CF who have pulmonary P. aeruginosa. In this study, 164 patients were randomized to receive 28 days of treatment with 75 mg aztreonam lysine (n=80) or volume-matched placebo (n=84) administered three times daily (TID) by the PARI eFlow® Electronic Nebulizer. Patients were followed for an overall study period of 42 days, with 14 days of observation after completing aztreonam lysine or placebo therapy. The mean age of patients treated with aztreonam lysine in the trial was 27.4 years. At baseline, the mean overall CFQ-R score in the respiratory symptoms domain was 60.7 points (on a scale of 100). The mean percent predicted FEV1 was 54.6 percent overall. Thirty-seven percent of patients had a predicted FEV1 less than or equal to 50 percent, indicating severe baseline impairment of lung function. After 28 days of treatment, patients in the aztreonam lysine group experienced a significant improvement in mean change from baseline of 9.71 points in the respiratory symptoms domain of the CFQ-R compared to patients receiving placebo (p=0.0005). Aztreonam lysine-treated patients also experienced significant improvements from baseline in pulmonary function, as measured by relative improvement of FEV1, with a treatment difference in mean change from baseline of 10.3 percent versus placebo (p<0.0001). Aztreonam lysine was also associated with significantly greater reductions in P. aeruginosa colony forming units (a measure of the amount of bacteria present in the lungs) at 28 days compared with placebo, with a treatment difference in mean change from baseline of -1.45 (log reduction, p<0.0001). Minor fluctuations in pseudomonas sensitivity to aztreonam were seen (as measured by minimum inhibitory concentrations) from baseline to the end of therapy. Long-term data are needed to fully assess this aspect of therapy. There was also a trend toward lower rates of hospitalization among aztreonam lysine-treated patients compared to placebo-treated patients (5.0 percent versus 14.3 percent, respectively, p = 0.0640). Aztreonam lysine was well-tolerated with a safety profile consistent with the expected symptoms of a patient with underlying CF disease. The most common treatment-emergent adverse events in this study were cough (47.5 percent), productive cough (16.3 percent), nasal congestion (13.8 percent), sore throat (12.5 percent) and dyspnea (shortness of breath) (8.8 percent). Among these, productive cough was reported significantly less frequently in the aztreonam lysine group compared to the placebo group. The remaining events were not significantly different between the placebo and aztreonam lysine groups. Limited interim data from AIR-CF3 (CP-AI-006), an open-label extension study of patients who participated in AIR-CF1 and AIR-CF2, will also be described by Felix Ratjen, MD, PhD, FRCPC, Head, Division of Respiratory Medicine, Sellers Chair of Cystic Fibrosis at The Hospital for Sick Children and Professor of Paediatrics at the University of Toronto, during a plenary session titled, "CF Drug Development: What's New?” on Friday, October 5. CFQ-R and FEV1 responses similar to what were seen in the placebo-controlled trials were reported after each of the first three 28-day courses of three times daily aztreonam lysine therapy given in 28-day on, 28-day off cycles. Aztreonam lysine for inhalation is an investigational therapy and has not yet been determined safe or efficacious in humans. About AIR-CF Phase III Clinical Program AIR-CF1 was one of three Phase III studies in the AIR-CF clinical program. The program, which also includes AIR-CF2 and AIR-CF3, was designed to determine the safety and efficacy of aztreonam lysine for inhalation for treatment of people with CF who have pulmonary P. aeruginosa. AIR-CF2 was a randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of a 28-day treatment course with aztreonam lysine for inhalation following a 28-day treatment course of tobramycin inhalation solution in people with CF who have pulmonary P. aeruginosa. Patients were randomized to receive 28 days of treatment with 75 mg of aztreonam lysine or volume-matched placebo each administered twice daily (BID) or TID by the PARI eFlow Electronic Nebulizer. Patients were followed for an overall study period of 126 days, with 56 days of observation after receiving aztreonam lysine for inhalation therapy or placebo. Positive results from this study were presented at the Cystic Fibrosis Therapeutics Development Network conference in Seattle, Washington on April 19, 2007 and at the European Cystic Fibrosis Society Conference in Belek, Turkey on June 14, 2007. AIR-CF3 is an ongoing open-label, multi-center study of patients who participated in the AIR-CF1 or AIR-CF2 studies. The primary objective of the study is to evaluate the safety of repeated exposure to aztreonam lysine for inhalation in people with CF. Each patient’s participation in the study will last up to 18 months. Patients will receive treatment with 75 mg of aztreonam lysine with the same regimen they received in AIR-CF1 or AIR-CF2 (BID or TID). About the Expanded Access Program In August 2007, Gilead initiated an expanded access program (EAP) to provide aztreonam lysine for inhalation to patients with CF and P. aeruginosa who have limited treatment options and are at risk for disease progression. The EAP is open to treatment centers in the United States for CF patients six years or older who have P. aeruginosa present in expectorated sputum or throat swab culture within two months prior to consent. The Cystic Fibrosis Foundation, through its affiliate pharmacy, Cystic Fibrosis Services, Inc. is assisting in drug distribution to treatment centers. Patients in the U.S. with severe lung function impairment as defined as having a FEV1 of less than 50 percent predicted or who have completed participation in the open-label trial AIR-CF3 are eligible to participate. For more information regarding the expanded access program or to request registration materials, physicians may call 1-800-490-2697 or log on to www.EAPforCF.com. Participating patients are evaluated at screening, at baseline, at Day 28 and at Day 56 visits, and then every two months thereafter. In this program, patients will receive aztreonam lysine, administered via the PARI eFlow Electronic Nebulizer, 75 mg TID, in 56-day cycles of therapy (28 days on drug followed by 28 days off) as provided by their physician until patients or physicians withdraw from participation in the study or the program is terminated by Gilead. About Aztreonam Lysine for Inhalation Aztreonam lysine for inhalation is an antibiotic candidate currently being studied in Phase III clinical trials as a treatment for people with CF who have pulmonary P. aeruginosa. Aztreonam has potent activity against gram-negative bacteria such as P. aeruginosa. Aztreonam formulated with arginine is a FDA-approved agent for intravenous administration. Aztreonam lysine for inhalation is a proprietary inhaled formulation of aztreonam and has been designated with orphan drug status in the United States and Europe. About PARI and the eFlow Electronic Nebulizer Aztreonam lysine for inhalation is delivered by a novel inhalation device, the eFlow Electronic Nebulizer, developed by PARI Pharma GmbH. eFlow is a quiet, portable nebulizer that enables efficient aerosolization of liquid medications via a vibrating, perforated membrane. PARI Pharma also contributed to the development and optimization of the drug formulation (aztreonam lysine for inhalation) for delivery via eFlow. Based on PARI's 100-year history working with aerosols, PARI Pharma is dedicated to advancing inhalation therapies by developing innovative delivery platforms and new pharmaceutical formulations that work together to improve patient care. About Cystic Fibrosis Today, more than 30,000 people in the United States have CF. CF is a chronic, debilitating genetic disease. A major characteristic of CF is production of abnormally thick, sticky mucus in the lungs that traps bacteria and predisposes patients to lung infections, which continually damage their lungs. Pulmonary infection with Gram-negative bacteria, particularly pulmonary P. aeruginosa, represents the single greatest cause of morbidity and mortality among CF patients. Currently there is no known cure for CF, and the goal of CF therapy is to control symptoms and prevent further lung damage. About NACFC Organized and funded by the Cystic Fibrosis Foundation, the North American Cystic Fibrosis Conference is the largest CF meeting of its kind in the world. More than 3,000 scientists and caregivers come together each year to share the latest research and help accelerate progress being made in the field of cystic fibrosis. For more information on the CF Foundation, visit www.cff.org. About Gilead Sciences Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia. This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risks that additional data from clinical studies may not warrant further development of aztreonam lysine for inhalation for the treatment of CF. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2006 and its Quarterly Reports on Form 10-Q for the first and second quarters of 2007, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements. For more information on Gilead, please call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or visit www.gilead.com.