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Novartis' Xolair coming for asthma
The Food & Drug Administration is reviewing data on a new anti-immunoglobulin E (IgE) compound that blocks the allergic triggers of severe asthma attacks and heads off symptoms, according to information presented at the recent American Academy of Allergy, Asthma & Immunology (AAAAI) meeting in New York.
"Xolair [omalizumab, Novartis and Genentech] is the only anti-IgE antibody therapy being studied for asthma control," investigator Jonathan Corren, M.D., from the Allergy Research Foundation Inc., Los Angeles, told Drug Topics. "It is associated with a dramatic reduction in symptoms and a better quality of life in patientsparticularly adultswith allergic asthma. This is so, even when they are on high doses of daily inhaled corticosteroids," he said.
Only a small percentage of the roughly 10 million Americans suffering from allergic asthma do not benefit from the range of available therapies, including bronchodilators and anti-inflammatory drugs, Corren noted. "But that minority of unresponsive and noncompliant patients has persistent exacerbations. Their emergency visits to the hospital drive up medical costs for everyone."
More than 5,000 people die from asthma attacks annually, according to the Centers for Disease Control & Prevention.
Two pivotal phase III trials of 1,071 adolescents and adults (median age, 40) with moderate to severe allergic asthma confirmed the safety and efficacy of this recombinant, humanized, monoclonal anti-IgE antibody as add-on therapy to inhaled steroids, Corren said. The trials were conducted in the United States and Europe.
Pharmacists should know that the dose was based on body weight and IgE concentrations in the bloodstream, he continued. "The minimum dose was 0.016 mg/kg IgE (IU/ml), administered by subcutaneous injection every two to four weeks for the 16 weeks of the trials.... The standard inhaled corticosteroid dosage was not reduced."
Several analyses of the trial data predicted which patients would best respond to omalizumab. "This is a new approach to therapy being used more and more often with new drugs," said researcher Sally Wenzel M.D., from the National Jewish Medical & Research Center, Denver. "Knowing the patient's level of responsiveness in advance helps the clinician decide whether [the patient] could benefit from having a newand probably priceydrug added on to standard treatment."
With omalizumab, the most difficult-to-treat patients benefited most, according to her group's analysis, Wenzel reported. "Those who responded best had the worst lung function, received the highest-standard inhaled steroid dose, and had at least one ER visit last year. In healthier patients, there was little difference between response to omalizumab and response to placebo."
She emphasized in an interview that while Xolair likely will be very expensivecosting perhaps $10,000 to $15,000 a year"this must be compared with the high costs of rehospitalization."
Other promising investigational treatments were also discussed at the AAAAI meeting:
Cytokines. Nearly 100 studies on cytokines in a variety of allergic diseases were presented. Many scientists believe the inflammatory cytokines (including interferons, tumor necrosis factor, and interleukins, among other cellular products from the immune system) maintain chronic inflammation in asthma to defend against antibodies that trigger the allergic cascade.
"We seek ways to use cytokines to regulate, amplify, or modulate inflammatory responses," said Corren at a media briefing on new asthma therapies. He was optimistic about the anti-Il 4 antibody being developed collaboratively by Protein Design Laboratory and GlaxoSmithKline and now in clinical trials. Hopeful as well about Immunex's new TNF-soluble receptor, he said that "it may block the pathologic effects of TNF."
New corticosteroids and nonsteroidal anti-inflammatory drugs. They are in various stages of development; these would retain anti-inflammatory efficacy with fewer systemic side effects. An example is tecastemizole (TEC, Sepracor), a third-generation antihistamine claimed to be nonsedating and without effects on the QT interval. The onset of action is within 20 to 30 minutes.
Naomi PFEIFFER. Researchers report on promising new anti-IgE agent for asthma.
Apr. 1, 2002;146:44.