Saturday, Mar 4, 2000
San Diego, Calif. -- March 4, 2000 --According to two Phase III studies presented today at the 56th Annual Meeting of the American Academy of Allergy, Asthma and Immunology, treatment with anti-IgE (olizumab/rhuMAb-E25), a recombinant humanized monoclonal antibody to IgE, has shown a decrease in the frequency of asthma exacerbations. Approximately 17 million Americans suffer from asthma, a chronic inflammatory lung disease that is often triggered by allergies and is characterized by airway obstruction, wheezing and coughing.
Results from the two randomized, double-blind, placebo-controlled studies showed that anti-IgE treatment reduced the number of asthma exacerbations. In both trials, asthma exacerbations were defined as symptoms requiring a doubling of inhaled steroids or initiation of oral steroids to maintain adequate asthma control. These studies corroborated results from an earlier Phase II clinical trial of anti-IgE recently reported in The New England Journal of Medicine. In addition, positive Phase III results of anti-IgE treatment for seasonal allergic rhinitis were presented last year at the 20th Annual Nordic Congress on Allergology.
Phase III Trial Design/Summary
In each of the two trials, asthma patients who were symptomatic despite taking inhaled corticosteroid therapy were given either subcutaneous anti-IgE (every two-to-four weeks), or placebo. Patients were monitored for asthma exacerbations over 28 weeks in two phases: 1) a 16-week stable treatment period that monitored patients taking either anti-IgE or placebo combined with inhaled steroids and rescue albuterol; and 2) a 12-week steroid reduction period (immediately following the stable treatment period), where the dosage of inhaled steroids was gradually reduced in both the anti-IgE and placebo groups. In the pediatric study, steroid dosage was reduced by 100 percent in more than half of the patients in the anti-IgE group, and by at least 71 percent in half of the placebo group patients.
"New Therapies: Late Breaking Mini-Symposium" - Anti-IgE Adult Study
One study, presented at the New Therapies: Late Breaking Mini-Symposium, examined the effects of anti-IgE in reducing asthma exacerbations in 525 adult asthma patients. In this trial, the percentage of anti-IgE patients experiencing asthma exacerbations was reduced in both the stable treatment period and the steroid reduction period.
During the stable treatment period, 14.6 percent (39 of 268 patients) of patients receiving anti-IgE demonstrated asthma exacerbations, versus 23.3 percent (60 of 257) of patients receiving placebo. During the steroid reduction period, 21.3 percent (57 of 268) of anti-IgE patients experienced asthma exacerbations compared to 32.3 percent (83 of 257) in the placebo group.
Upper respiratory infection (84 of 268 anti-IgE patients vs. 76 of 257 placebo patients) and viral infection (71 of 268 anti-IgE patients vs. 80 of 257 placebo patients) were the most frequently reported adverse events in both groups. The percentages of patients with one or more adverse events were similar between groups: 88 percent for the anti-IgE group and 89 percent for the placebo group. Serious adverse events (other than asthma exacerbations) were reported in six anti-IgE patients (anaphylaxis, myocardial infarction, diverticulitis, fracture, tendinitis, depression) and six placebo patients (chest pain, cardiac arrest, appendicitis, goiter, viral infection, intervertebral disk disorder), but no event was reported more than once and none were judged to be drug-related by investigators. The single anaphylaxis case occurred in a patient with known sensitivity to quinolones 30 minutes after treatment with a quinolone antibiotic. Safety data from the five-month extended follow-up phase of the trial are pending.
"New Therapies: Late Breaking Mini-Symposium" - Anti-IgE Pediatric Study
The second study examined the safety of anti-IgE treatment and the potential for reducing inhaled steroid usage and the exacerbation of asthma symptoms in 334 asthmatic children aged 6-12 years. In this trial, the percentage of anti-IgE patients experiencing asthma exacerbations was reduced during both the stable treatment period and the steroid reduction period. Additionally, 55 percent (124 of 225) of anti-IgE patients completely withdrew from inhaled steroids during this phase, compared to 39 percent (43 of 109) of placebo patients.
Headache (80 of 225 anti-IgE patients vs. 33 of 109 placebo patients) and upper respiratory tract infection (78 of 225 anti-IgE patients vs. 39 of 109 placebo patients) were the most frequently reported adverse events. The percentages of patients with one or more adverse events were similar between groups: 89 percent for anti-IgE and 87 percent for placebo patients. Serious adverse events (other than asthma exacerbations) were reported in four anti-IgE patients (accidental injury, appendicitis, gastritis, ear infection) and four placebo patients (fracture (2), pneumonia, upper respiratory tract infection), and none of the events were judged to be drug-related by investigators. Safety data from the five-month follow-up phase of the trial are pending.
IgE is an antibody that triggers the release of inflammatory mediators, such as histamine, prostaglandins and leukotrienes, thereby causing the symptoms associated with allergic reactions. The release of these inflammatory substances plays a major role in allergic disease, such as allergic asthma and seasonal allergic rhinitis.
Anti-IgE works by binding to circulating IgE in the blood. The treatment is intended to intervene early in the allergic process by targeting IgE, the source of allergic inflammation for all allergens. Anti-IgE prevents IgE from binding to mast cells, thereby blocking the consequent release of inflammatory mediators.
Genentech, Inc., Novartis Pharma AG and Tanox, Inc. are collaborating on Phase III clinical development of anti-IgE. The safety and efficacy of anti-IgE in Phase III clinical investigations must be confirmed by the U.S. Food and Drug Administration as well as regulatory authorities in other countries as part of the global market registration process before any definitive conclusions can be made. The companies plan to file for regulatory approval in the US and in Europe by mid-2000.
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures, and markets human pharmaceuticals for significant unmet medical needs. Thirteen of the currently approved biotechnology products stem from Genentech science. Genentech markets eight biotechnology products directly in the United States. The company has headquarters in South San Francisco, California, and is traded on the New York Stock Exchange under the symbol DNA.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG, a world leader in healthcare with core businesses in pharmaceuticals, consumer health, generics, eye-care, and animal health. In 1999, the Group (including Agribusiness) achieved sales of USD 21.7 billion and invested more than USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis employs about 82,400 people and operates in over 140 countries around the world. The Group recently announced plans to spin off its Crop Protection and Seeds sectors and to merge them with the agrochemicals business of AstraZeneca in the second half of 2000.
Tanox, Inc., incorporated in 1986, is a biotechnology research and development company in Houston, Texas. Tanox identifies and develops therapeutic monoclonal antibodies designed to treat diseases involving or affecting the human immune system. Tanox is collaborating in the development of certain anti-IgE antibodies with Novartis Pharma AG and Genentech Inc.
# # #