Once-a-Week Inhaled Treatment Helped Stabilize Lung Function and Was Generally Well Tolerated
MADRID, SPAIN - Results of a Phase I/II trial of NUVANCE™ (soluble IL-4 receptor), an investigational once-a-week inhaled asthma treatment, suggest the drug was generally well tolerated and helped stabilize lung function for up to 12 weeks following discontinuation of inhaled corticosteroids, Immunex Corporation (NASDAQ: IMNX) announced today. These results were presented today at the European Respiratory Society meeting in Madrid, Spain.
"Asthma has reached epidemic growth levels. IL-4 inhibition may change the way physicians think about asthma," said Dr. Larry Borish, associate professor in medicine, University of Virginia Medical Center and principal investigator for the NUVANCE trial. "The data presented today provide the foundation for further study of NUVANCE and IL-4 inhibition in asthma."
NUVANCE, a recombinant human version of a naturally occurring protein, represents a novel investigational approach to treating asthma. NUVANCE acts by binding to Interleukin-4 (IL-4), a protein that is present in asthmatic lungs. The binding of NUVANCE to IL-4 renders the bound IL-4 biologically inactive, which may reduce the IL-4 driven signs and symptoms of asthma.
This placebo-controlled, randomized, double-blind, Phase I/II trial was conducted in 62 adults with moderate persistent asthma, in which symptoms such as wheezing, shortness of breath and coughing occur regularly. Prior to the study, all patients were dependent on inhaled corticosteroids, daily medication intended to relieve inflammation of the airways. All patients discontinued inhaled corticosteroids when study treatment was started.
The study assessed the safety and pharmacokinetics (absorption, distribution and elimination) of inhaled NUVANCE following discontinuation of inhaled corticosteroids. Investigators compared three doses of NUVANCE, 0.75 mg, 1.5 mg or 3.0 mg, to placebo and administered each treatment by inhalation once weekly for up to 12 weeks.
Overall, treatment with NUVANCE was generally well tolerated. No serious adverse events related to study drug were reported. The most frequently reported side effects were headache (13%), mild nausea (13%), respiratory infection (11%) and pain (11%).
Following discontinuation of inhaled corticosteroids, patients in the 3 mg NUVANCE group experienced continued asthma control over the 12 week treatment period with minimal decline in forced expiratory volume (FEV1), a mean of -2.2%, compared to a greater decline in FEV1 in the placebo group, a mean of -13.2%. FEV1 is a standard measurement of lung function that measures how much air a person can expel in one second. It is a clinical marker used to evaluate asthma severity, with a reduction in FEV1 indicating a worsening of asthma.
The results described herein are based on investigational data analyzed by Immunex. These data have not been reviewed by the U.S. Food and Drug Administration (FDA) as part of an application for regulatory approval.
The results reported today are consistent with the findings of an earlier single-dose pilot study with NUVANCE in moderate persistent asthmatics that was presented at the 1998 American Academy of Allergy, Asthma and Immunology Conference (AAAAI).
A Phase II clinical trial of NUVANCE is currently underway to evaluate the safety and efficacy of the drug for longer-term control of asthma. The study will include 180 people with asthma at 19 leading asthma clinics in the United States. People with asthma interested in participating in the clinical trial program for NUVANCE should contact the Immunex Professional Services Department at 1-800-IMMUNEX.
About Asthma
Asthma is a chronic inflammatory disorder of the airways, with periodic acute worsening that can significantly limit a patient's normal activities. Symptoms include coughing, wheezing, and tightness in the chest. Approximately 17 million Americans have asthma, and more than half of these people are candidates for a long-term control therapy, meaning they need to use their rescue therapy twice or more a week.
Asthma results in millions of emergency room visits per year and more than 5,000 deaths annually, according to the U.S. Centers for Disease Control and Prevention. Projected to cost more than $14.5 billion annually in both direct and indirect costs to the U.S. economy by the year 2000, asthma causes more than 100 million days of restricted activity among people with asthma, and there are more than 500,000 hospitalizations related to asthma each year.
About IL-4
Interleukin-4 (IL-4) is a naturally occurring cytokine, or immune system protein, that has been commonly associated with the development of asthma and allergies. It binds to specific IL-4 receptors (IL-4R) on the surface of cells in the body or to naturally occurring soluble receptors that circulate throughout the body. Increased levels of IL-4 appear to be related to increased severity of asthma that results in difficulty in breathing.
IL-4 promotes the differentiation of naive T helper lymphocytes into Th2 lymphocytes. Th2 lymphocytes secrete cytokines such as IL-4, IL-5, IL-9 and IL-13, which are key mediators of asthmatic inflammation. IL-4 is one of the molecules that induce mucous production by lung mucous glands, contributing to airway obstruction. IL-4 regulates expression of the adhesion molecule VCAM-1 which interacts with the VLA4 molecule on the surface of eosinophils. This interaction allows eosinophils to migrate from the blood and into the lung tissue resulting in inflammation. IL-4 induces B cell proliferation and the production of antigen-specific IgE that is required to trigger allergic response. Antigen-specific IgE causes mast cells to release inflammatory "mediators," such as histamines and leukotrienes, and these create bronchoconstriction.
Immunex scientists used recombinant DNA technology to produce a soluble IL-4 receptor, a molecule the company named NUVANCE. When IL-4 binds with NUVANCE (soluble IL-4 receptor) instead of cell-surface IL-4R, the effects of IL-4 may be blocked.
Immunex Corporation is a biopharmaceutical company dedicated to developing immune system science to protect human health. The company's products offer hope to patients with cancer, inflammatory and infectious diseases.
American Home Products Corporation owns a majority interest in Immunex. AHPC is one of the world's largest research-based pharmaceutical and health care products companies and is a leading developer, manufacturer and marketer of prescription drugs and over-the-counter medications. It is also a leader in vaccines, biotechnology, agricultural products and animal health care.
NOTE: This news release contains forward-looking statements that involve risks and uncertainties, including risks associated with clinical development, regulatory approvals, product commercialization and other risks described from time to time in the SEC reports filed by Immunex, including the most recently filed Form 10-Q.
An electronic version of this news release - as well as additional information about Immunex of interest to investors, customers, future employees and patients - is available on the Immunex home page at www.immunex.com .