GAITHERSBURG, Md. - An FDA advisory panel said Xolair appears to work well enough in moderate to severe allergic asthmatic patients to win regulatory approval.
The Pulmonary-Allergy Drugs Advisory Committee voted unanimously that data presented by Genentech Inc. demonstrated a favorable risk-benefit for the use of Xolair as a means of reducing asthma exacerbation rates and controlling symptoms of the illness. The panel's recommendation is forwarded to the FDA, which is not bound by the advice, but panel recommendations often portend the FDA's opinion.
The Xolair biologics license application was submitted by South San Francisco-based Genentech Inc. and its partners, Novartis Pharma AG, of Basel, Switzerland, and Tanox Inc., of Houston. The companies expect a decision from the FDA by June 20, Xolair's Prescription Drug User Fee Act date.
After Thursday's meeting here, Genentech and its partners told BioWorld Today they expect a favorable decision on the first-in-class monoclonal antibody to human IgE. Cynthia Hogan, vice president for the respiratory and dermatology therapeutic franchise at Novartis in East Hanover, N.J., said the companies expect to launch "within weeks" of approval.
Genentech is seeking approval for Xolair (omalizumab) as a maintenance therapy for the prophylaxis of asthma exacerbations and control of symptoms in adults and adolescents (12 years and above) with moderate to severe allergic asthma that is inadequately controlled despite the use of inhaled corticosteroids. Xolair is a subcutaneous injection administered once or twice monthly.
While casting favorable votes, most panel members said Xolair should be limited to patients between the ages of 12 and 65 who have been diagnosed with allergic asthma by way of a skin test.
Wall Street expects Xolair to cost between $7,500 and $10,000 per year per patient, generating about $600 million at peak (year 2008) in the allergic asthma indication for Genentech and its partners.
Following the meeting, Charles Johnson, senior director of specialty biotherapeutics at Genentech, wouldn't discuss estimated costs with reporters, but did say the U.S. market for allergic asthma is about 500,000 patients per year.
Xolair works by targeting the antibody IgE, an underlying cause of allergic asthma. In allergic patients, the binding of IgE and allergens to mast cells causes the mast cells to release inflammatory chemical mediators, which in turn can lead to the symptoms of allergic asthma.
Over a number of years, Xolair has been tested in upward of 6,000 patients. Genentech's BLA included efficacy data from two pivotal Phase III trials that enrolled in excess of 500 patients each, ages 12 to 75 years old. The smaller of the two, Study 008, evaluated moderate to severe allergic asthma that was uncontrolled despite treatment with inhaled corticosteroids and frequent use of beta-agonist rescue medication. Study 009 evaluated moderate to severe allergic asthma that was uncontrolled despite treatment with inhaled corticosteroids and frequent use of beta-agonist rescue medication.
James Kaiser, an FDA reviewer, pointed out that while Xolair reached its primary endpoint of reducing exacerbations, non-Caucasian patients were somewhat underrepresented in the trials. Several panel members jumped on that issue, saying inner city minorities - particularly children - represent a large number of asthma sufferers. Johnson said trials in children under 12 years of age are expected to begin later this year.
Also, panelists were concerned about Genentech's lack of data on smokers.
"By mechanism of action, there doesn't appear to be a reason that this shouldn't work in smokers, but I would like to see more data," said Robert Fink, a panel member and medical director of pediatric pulmonary medicine at Children's Medical Center in Dayton, Ohio.
Another panel member, Michael Schatz, a physician with Southern California Permanente Medical Group in San Diego, added that it wouldn't be right to limit Xolair to non-smokers, particularly since many asthmatics smoke.
In advance of the meeting, several media accounts suggested that Xolair could be linked to an increased risk of cancer. In his presentation, FDA reviewer Dwaine Rieves discussed the issue, concluding that malignancies were "uncommon" occurrences.
Genentech reported that malignant neoplasms occurred in 20 of 4,127 (0.5 percent) of Xolair-exposed patients compared to five of 2,236 (0.2 percent) of control patients. Excluding non-melanoma skin cancer, malignancies were detected among 16 (0.4 percent) of Xolair patients and two (0.1 percent) control participants.
Rieves said while there were more malignancies in the treatment group, the findings were not definitive and Johnson said there's no evidence that Xolair is linked to cancer.
Graca Dores, a panel member and cancer prevention fellow at the National Cancer Institute in Bethesda, Md., said there's not enough evidence either way to determine if Xolair has a link to cancer.
"People with malignancies should be excluded from these trials because it's easier to study," she said. "People who take this medication really need to be followed for long-term data."
For the most part, Xolair would be prescribed for long-term, chronic use. Novartis and Genentech will co-promote Xolair in the U.S., where each will have a sales force. Novartis will market it outside the U.S. Novartis received approval for Xolair in Australia, but withdrew its European application in favor of submitting more data. The application is expected to be resubmitted in the first half of 2004.
Under terms of the agreement, Tanox will receive a 10 percent royalty on U.S. and European sales (See BioWorld Today, July 10, 1996.)
Genentech's stock (NYSE:DNA) rose $1.57 Thursday to close at $40.05.