New Drugs Engineered to Fight Asthma.

Environmental allergens such as those associated with dust mites and cockroaches can trigger asthma attacks in predisposed individuals when they overwhelm the immunoglobulin E (IgE) cascade, a system believed to protect the body against parasitic invasion. About 5,000 people die each year from asthma attacks, and doctors believe that all those deaths could be prevented. At the American Academy of Allergy, Asthma and Immunology annual meeting, held 3-8 March 2000 in San Diego, California, doctors detailed how investigational bioengineered drugs target and soak up IgE and interleukin-4 (IL-4), key modulators of the IgE cascade. The drugs may eventually replace corticosteroids, currently the drug of choice, as preventive medication.

Henry Milgrom, a senior staff physician at National Jewish Medical and Research Center in Denver, Colorado, described progress in clinical trials with anti-IgE, a compound developed jointly by the drug companies Genentech, Novartis Pharma AG, and Tanox. "This is a breakthrough--anti-IgE was designed to perform a specific function in suppressing a disease process and it works," Milgrom said.

Among the 268 adult patients suffering from moderate to severe asthma who received injections of anti-IgE in the first phase of a 28-week study, only 14.6% had asthma attacks, compared with 23.3% of the 257 patients on placebo. There were also reduced exacerbations of asthma during the second phase of the study when steroid medication was withdrawn.

In a second study involving 334 asthmatic children, 55% of the children receiving anti-IgE were able to discontinue all steroid medication without suffering asthma attacks, compared to about 39% of patients receiving placebo injections.

"This is an exciting approach to treatment of asthma," said Michael Wein, chief of allergy at Indian River Memorial Hospital in Vero Beach, Florida. "If you found something to remove IgE from the body, you wouldn't have allergies." Milgrom said anti-IgE also has potential for people who have food or latex allergies, atopic dermatitis, and other conditions. He said a new drug application for anti-IgE will be filed with the Food and Drug Administration this summer.

Larry Borish, an associate professor of medicine at the University of Virginia Medical Center in Charlottesville, reported that another new drug, IL-4R (for IL-4 receptor), is effective for 5-7 days with just one inhaled dose. IL-4 is responsible for the respiratory inflammation associated with asthma. Borish said the drug soaks up circulating IL-4 like a sponge.

Borish reported administering either placebo or three different dosages of IL-4R to 15-16 patients per group in 12 weekly inhalations. The patients were all suffering from moderate to severe asthma and had been taking inhaled corticosteroid medication, which was stopped on the first day of the study. The group taking the placebo showed a significant decline in lung function, whereas this decrease in function did not occur in the treatment group, Borish said, demonstrating the efficacy of the experimental drug. Borish said a larger study of IL-4R will be reported this summer.

In almost all chronic diseases, long-term patient noncompliance is probably the major reason why treatment eventually fails. So, says Charles Feldman, an associate professor of pediatrics at Columbia University in New York, the great promise of IL-4R is that if further studies prove its effectiveness, its ease of use should improve patient compliance--a key to keeping asthma in check.