By Lisa Seachrist
WASHINGTON — The FDA approved the first monoclonal antibody designed to fight cancer Wednesday when it granted IDEC Pharmaceuticals Corp. the right to market Rituxan for the treatment of low-grade non-Hodgkin's lymphoma (NHL) recurrences.
Coming 20 years after the discovery of monoclonal antibodies, Rituxan is not, as many had hoped, a "magic bullet" to treat cancer. Nevertheless, it is a largely non-toxic option for patients for whom other standard treatments have failed.
"The remarkable thing is that this technology was described in 1975," said William Rastetter, chairman, CEO and president of the San Diego company. "It speaks to the difficulty of translating academic science to the marketplace."
Rastetter said that Rituxan should be available to the NHL patient community in the next couple of weeks. With its U.S. partner Genentech, Inc., of South San Francisco, IDEC has built up an inventory and trained a sales force. Rastetter noted that all that was left was to print up package inserts and labels for the product.
"This approval is a tribute to a couple of partnerships with Genentech and the FDA," Rastetter said. "It would not have happened as quickly without them."
Rituxan (rituximab) is a chimeric monoclonal antibody aimed at the CD20 antigen found on mature B cells and most NHL tumors. To prevent people from developing antibodies to the drug, Rituxan is composed of a section of mouse antibody that binds to the CD20 antigen attached to the constant region of the human antibody. The company doesn't know exactly how the drug recruits the immune system to destroy NHL cell but in vitro studies indicate the drug can kill cells by antibody-mediated cell death, complement-mediated cell death and apoptosis.
Non-Hodgkin's lymphoma is a malignancy of the antibody-producing cells of the immune system. Approximately 240,000 people in the United States have NHL, a number which has grown by 75 percent since the early 1970s. Sixty-five percent of all NHL patients have a low-grade or follicular lymphoma, characterized by multiple relapses over the six- to seven-year course of the disease, which is incurable.
On July 25, 1997, an FDA advisory panel unanimously recommended the agency approve Rituxan based on clinical data that showed, of 166 patients studied with advanced low-grade or slow-growing NHL, tumors shrank by at least one-half in 48 percent of the patients who completed the treatment, with 6 percent experiencing complete remissions.
IDEC estimates that Rituxan is indicated for treating half of all living NHL patients, approximately 125,000. Connie Matsui, vice president for planning and resource development at IDEC, told BioWorld Today that because Rituxan is relatively non-toxic, community oncologists will likely turn to Rituxan before moving onto more aggressive therapies.
Monoclonal antibodies and their applications in clinical practice will be discussed by leading experts at the upcoming 39th Annual Meeting of the American Society of hematology (ASH). "Monoclonal Antibody Therapies for Non-Hodgkin's Lymphoma," a symposium sponsored by IDEC and Genentech, will be held Dec. 5 in the San Diego Convention Center.
In addition to the symposium, results of two new Rituxan studies also will be presented in poster sessions at ASH: "Retreatments with Rituxan have significant efficacy, do not cause HAMA, and are a viable minimally toxic alternative in relapsed or refractory non-Hodgkin's lymphoma" (abstract #2269); and "Rituxan interim analysis of a Phase II study of one weekly times 8 dosing in patients with relapsed low-grade or follicular non-Hodgkins' lymphoma" (abstract #2212).
Coulter Pharmaceuticals, of Palo Alto, Calif., has its own version of a radio-labeled CD20 monoclonal antibody in Phase III trials and expects to file a BLA by the end of 1998.
IDEC discovered Rituxan and developed the product in collaboration with Genentech, F. Hoffman-LaRoche Ltd., of Basel, Switzerland, and Zenyaku Kogyo Co. Ltd., of Tokyo.
IDEC and Genentech will copromote Rituxan in the U.S., Roche will market Rituxan in the rest of the world pending approvals, and Zenyaku will market the product in Japan. *