By Lisa Seachrist

Washington Editor

BETHESDA, Md. -- An FDA advisory panel unanimously recommended the agency grant marketing clearance to Rituxan (rituximab) for the treatment of patients suffering from relapsed or refractory low-grade non-Hodgkin's lymphoma. Should the FDA approve the drug, the IDEC Pharmaceuticals Inc. and Genentech Inc. product will be the first monoclonal antibody sold for treating cancer.

With a 12-0 vote, the members of the Biological Response Modifiers Advisory Committee declared they were persuaded rituximab, also called IDEC-C2B8, was both safe and effective.

"I think the data are clear that this is as good as [standard chemotherapy agents] in treating non-Hodgkin's lymphoma," said panel member Charles August, director of the bone marrow transplantation program at the Miami Children's Hospital.

Virginia Broudy, acting chairwoman of the panel and an associate professor of medicine at the University of Washington School of Medicine, in Seattle, added, "I completely concur. This is an agent we should add to our armamentarium."

"We are very happy," said Christine White, senior director of clinical oncology at IDEC, in San Diego. "We've worked very hard and have a rigorous definition of response. As a result our data are very believable."

Non-Hodgkin's lymphoma (NHL) is a malignancy of the antibody-producing cells of the immune system. Approximately 240,000 people in the United States have NHL, which has grown in incidence 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 incurable disease.

Currently, standard therapy includes chemotherapy regimens and radiotherapy as well as autologous bone marrow transplants (ABMT). However, with each relapse, a patient is less likely to respond to treatment and will have a shortened period of remission between relapses.

Antibody's Mechanism Of Action Unclear

Rituximab is a chimeric monoclonal antibody aimed at the CD20 antigen found on mature B cells and most NHL tumors. In order to prevent people from developing antibodies to the drug, rituximab is composed of a section of mouse antibody against CD20 attached to a constant region of human antibody. The company doesn't know exactly how the antibody recruits the immune system to attack lymphoma; however, in vitro studies indicate the drug can kill cells by antibody-mediated cell death, complement-mediated cell death and apoptosis.

IDEC and Genentech, of South San Francisco, presented data on 203 patients who had received a standard course of the drug -- an infusion of 375 mg/meter2 of monoclonal antibody given once weekly four times over 22 days. Rituximab reduced the size of tumor by 50 percent or more in 48 percent of the treated patients. Six percent experienced a complete response, with no signs of tumor remaining. In addition, the median duration of the response has not yet been achieved at 9.2-plus months.

Ninety-five percent of all the patients suffered some sort of adverse event, ranging in severity from fever, nausea, chills and headache to arrythmias. The vast majority of these side effects were transient and mild, but 10 percent of patients experienced bronchospasm and another 10 percent suffered from low blood pressure.

The panel, however, wasn't particularly concerned with the side effects associated with the drug.

"Given the spectrum of toxicities for most of the drugs we give to NHL patients," said Carole Miller, assistant professor of oncology at The Johns Hopkins Oncology Center, in Baltimore, "the risks are acceptable. This drug presents a good opportunity for patients to receive treatment without the side effects associated with chemotherapy."

W. French Anderson, director of the gene therapy laboratory at the University of Southern California School of Medicine, in Los Angeles, pointed out that because rituximab kills mature B cells, people receiving the drug are unlikely to be able to mount immune responses to any new pathogens they may come across. He urged the company to study the long-term immune effects the drug may have.

White said the company is continuing to study rituximab and also will investigate whether it is effective in other hematopoetic malignancies where the CD20 antigen is expressed, such as chronic lymphocytic leukemia.

The FDA isn't required by law to follow the recommendations of its advisory panels, but it usually does.

Should the agency approve rituximab, it will be the first monoclonal antibody on the market for use in oncology patients in the U.S., but it is not likely to be the last.

Coulter Pharmaceuticals, in Palo Alto, Calif., has its own version of a radiolabeled CD20 monoclonal antibody in Phase III trials and expects to file a biologics license application by the end of 1998.

IDEC and Genentech retained marketing rights to rituximab in the U.S. F. Hoffmann-La Roche Ltd., of Basel, Switzerland, licensed the drug for sale in Europe and Zenyaku Kogyo Co. Ltd., of Japan, has marketing rights in that country.

IDEC's stock (NASDAQ:IDPH) closed Friday at $26.375, down $1.562. Genentech ended the day at $57.625, up $0.375. *