By Lisa Seachrist
WASHINGTON — Less than five months after filing a biologics license application (BLA) for Herceptin, a monoclonal antibody for the treatment of metastatic breast cancer, Genentech Inc. received marketing clearance from the FDA.
The approval comes weeks after an FDA advisory panel unanimously recommended the drug as a treatment for metastatic breast cancer in combination with paclitaxel as a first-line agent and as a single agent in women who have failed other therapies. The FDA followed the panel's advice and late Friday evening approved the drug for marketing.
"This is a great example of industry, government and advocacy groups working together," said Marie Kennedy, a spokeswoman for South San Francisco-based Genentech. "The good news is for the patients who don't have many other good options. And this approval really speaks to the promise of biotechnology coming to fruition."
Kennedy noted several advocacy groups formed a coalition called Herceptin NOW to encourage the agency to approve the drug before the Sept. 26 cancer rally in Washington, "The March: Coming Together to Conquer Cancer."
"We had no idea whether or not it could be done, but the FDA really worked with us beyond the call of duty to meet that deadline," Kennedy said. "Vice President [Al] Gore was able to mention a new breast cancer drug was approved late Friday night."
In anticipation of the approval, Genentech had ramped up its production of the drug, which will be available in mid-October to medical oncologists and their patients. The firm, however, has yet to set a price for Herceptin.
The drug is a humanized monoclonal antibody against the growth factor receptor HER2. Approximately one-third of all breast cancers overexpress the HER2 gene, littering the surface of cells with receptors that fuel the growth of cancer. As a result, breast tumors that overexpress HER2 are especially aggressive.
Herceptin does not kill breast cancer cells. Instead, it neutralizes the activity of the receptors and slows tumor growth.
However, because the drug only works for the proportion of women who have a tumor that overexpresses HER2, patients must have their tumors tested in order to determine whether the drug will be effective. The FDA also approved on Friday a testing kit produced by Dako Corp., of Carpinteria, Calif., a subsidiary of Dakopatts A/S, of Copenhagen, Denmark.
Dako Test Cleared To Identify Herceptin Patients
That immunohistochemical kit, Hercep Test, is specifically indicated for use in identifying breast cancer patients who could benefit from treatment with Herceptin. Dako licensed the patent rights and know-how from Genentech to develop the kit.
"Their test was developed and based on our clinical trial assay," Kennedy said. "Dako had the experience in cancer to make this test available. It was a very synergistic relationship for us."
Once a patient is deemed to have a HER2 positive tumor, she will receive weekly infusions of Herceptin at her oncologist's office until her tumor progresses. In clinical studies of the drug, Herceptin showed a survival benefit among women with metastatic breast cancer. Seventy-nine percent of patients who received Herceptin plus chemotherapy were alive after one year, compared to 68 percent of patients who received chemotherapy alone.
Herceptin can cause infusion reactions. However, the most serious side effect is cardiac dysfunction, characterized as heart failure. The problem was especially pronounced when patients received both Herceptin and anthracycline therapy — the latter of which is known to cause heart problems alone. Cardiac dysfunction discovered in the clinical trials responded to standard cardiac medicines.
The company is continuing to explore uses for Herceptin, including studies of the drug in combination with other chemotherapy agents. Genentech also plans to study Herceptin as an adjuvant therapy in women who have had their primary cancer removed in an attempt to stymie metastasis. The drug may also be useful in treating other tumors that express HER2, such as ovarian, prostate, lung and colon cancer.
Genentech, PDL Ink Antibodies Licensing Deal
In addition to receiving FDA approval, Genentech announced that it had signed a cross-licensing deal with Protein Design Labs Inc. (PDL), of Fremont, Calif., covering humanized monoclonal antibodies.
Under the agreement, Genentech will pay a $6 million up-front, non-creditable, non-refundable fee to PDL and PDL will pay a similar fee of $1 million to Genentech for the rights to license particular antibodies under specified patents and patent applications held by the other company.
In essence, the deal provides a means for the two companies to avoid a protracted patent infringement battle. PDL owns patents in the U.S. and Europe that it believes cover most humanized antibodies. Genentech has patents and applications which it believes cover the expression of recombinant antibodies and certain chimeric and humanized antibodies.
Each company will be able to license antibodies under the other company's relevant patents for a $1 million fee plus royalties. The move is in accordance with PDL's philosophy of widely offering licenses to its technology, said Jon Saxe, president of PDL.
"With Genentech, this is not only a big company, but the biggest single player in monoclonal antibodies," Saxe said. "By entering into this agreement, they are endorsing our patents. If they choose to designate Herceptin as a product licensed under our patent, there will be the promise of immediate significant revenue as well."
Genentech, however, has yet to decide whether Herceptin will be covered under the patent.
The company's stock (NYSE:GNE) closed Monday at $71.687, down $0.25. PDL's stock (NASDAQ: PDLI) ended the day at $24.937, down $0.062. *