Genentech Inc. and its partners finalized the biologics license application for the asthma product Xolair on Thursday by submitting an amendment that includes safety data from a 1,899-patient trial that was expanded on the request of the FDA.
Genentech, of South San Francisco, and collaborators Novartis Pharma AG, of Basel, Switzerland, and Tanox Inc., of Houston, expect the FDA to take action by June 19, the six-month deadline under the Prescription Drug User Fee Act.
The amendment, referred to by Shelly Schneiderman-Ducker, Genentech's manager of corporate communications, as a "major amendment" in FDA terms, eliminates seasonal allergic rhinitis (hay fever) as a requested indication and focuses on moderate to severe allergic asthma in adult and adolescent patients.
Schneiderman-Ducker said in the complete response letter issued in July 2001 for Xolair (omalizumab), the FDA sought additional preclinical and clinical data because of the diversity and size of the asthma and hay fever markets. According to Genentech figures, asthma affects 17 million people in the U.S., and hay fever affects about 40 million.
"So we did two things: We temporarily took seasonal rhinitis off the table and expanded our ongoing ALTO trial, which had safety measures as an endpoint, from under 1,000 patients to 1,899," Schneiderman-Ducker said. "We did not conduct another trial."
The expanded database in the amendment has information in it representing 6,000 patients, including the 1,899 ALTO patients, as well as 4,000 who have been treated with the product.
The companies describe Xolair as a first-in-class monoclonal antibody to IgE. In allergic patients, the binding of IgE and allergens to mast cells triggers the mast cells to release inflammatory mediators, such as histamine and leukotrienes, which can lead to the symptoms and inflammation of allergic asthma. By binding to IgE antibodies, Xolair inhibits IgE from attaching to mast cells, disrupting an allergen's ability to trigger the release of chemical mediators, which lead to symptoms.
Of the amendment submission, Ashraf Hanna, director of strategic planning for Tanox, told BioWorld Today, "We are very pleased that it has reached this milestone and are looking forward to Xolair being on the market to help those patients suffering from asthma."
Each of the three partners was separately developing its own anti-IgE antibodies before joining forces in the mid-1990s. The companies shared in the development costs.
Under terms of the agreement, Tanox will receive a 10 percent royalty on U.S. and European sales. Genentech and Novartis would not release financial details about the agreement.
However, representatives from each company said 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.
While Novartis received approval for Xolair in Australia, the company withdrew the application in Europe in order to submit additional information. A spokesman for Novartis said he expects the application to be resubmitted in the first half of 2004.
Genentech's stock (NYSE:DNA) closed Thursday at $34.35, down 67 cents, while Tanox's shares (NASDAQ:TNOX) closed at $10.07, down 34 cents.