The Food and Drug Administration yesterday for the first time approved the use of a revolutionary biotechnology treatment with long-range potential for combating a wide array of serious diseases and with immediate value in preventing rejection of kidney transplants.
In announcing the approval, FDA Commissioner Frank Young said it represents a research payoff that will have "major impact" on the estimated 7,000 Americans a year who receive kidney transplants, two-thirds of whom suffer a rejection episode serious enough to require treatment.
With further testing, the Nobel Prize-winning method -- known as monoclonal antibody therapy -- may later be use to prevent rejection of other transplanted organs and to "treat some of mankind's most serious illnesses, eventually including some cancers," he said.
Monoclonal antibodies, special protein molecules, are biotechnology's attempt to create medicine's fabled "magic bullet," a drug that goes straight to its target and fights harmful organisms and tissues without affecting innocent cells.
In this case, the monoclonal antibody was selected to search out and attack immune cells in the body that are responsible for rejection of transplanted kidneys.
The drug will be marketed by Ortho Pharmaceutical Corporation of Raritan, N.J., under the trade name "Orthoclone OKT*3."
The approval of a monoclonal antibody for treatment comes 11 years after the technology was developed in Cambridge, England, by Georges Kohler and Cesar Milstein. The researchers won the 1984 Nobel Prize in medicine for their discovery, which was cited as "one of the most important methodological advances in biomedicine during the 1970s."
More than 150 uses of monoclonal antibodies have been approved for diagnostic tests outside the body since the early 1980s, from pregnancy tests to venereal disease detection, said FDA officials.
But it has taken longer to demonstrate the safety and effectiveness of using them to treat patients. Yesterday's action was the first to allow commercial marketing of a monoclonal antibody for this purpose.
A monoclonal antibody is made in special cell factories that can produce identical copies, or clones, of the protein. The hybrid cells, called hybridomas, are formed by the fusion of mouse cancer cells, which grow profusely, with antibody-producing white cells taken from mice.
Ortho officials said that in a national clinical trial of the new product, acute rejections of newly transplanted kidneys were reversed in about 94 percent of patients receiving monoclonal antibody intravenously, a significant increase over the 75 percent reversal with conventional steroid drugs. In a second study, Orthoclone rescued 65 percent of patients who had not responded well to standard therapies used to help fight rejection, Ortho said.
While high doses of steroids suppress the entire immune system and can have serious side effects, Ortho said its new product targets the specific immune cells involved in rejection. It did produce flu-like symptoms, such as fever, chills and sometimes nausea and vomiting, it said.
If rejection occurs, a kidney is often lost. According to the company, in 1984, more than 1,900 patients who had received kidney transplants were returned to regular dialysis to cleanse their blood when their transplants lost this vital function. Demand for transplants far outstrips supply, it said, with donor kidneys unavailable to 8,000 Americans who wanted them in 1984.
Government approval of Orthoclone is specific to short-term episodes of kidney rejection. Other drugs are used for long-term treatment of such patients. And, although it is expected to be studied for other types of transplants, FDA's Young cautioned that the drug "not be used willy-nilly" until more research is completed.
Dr. Dan Longo of the National Cancer Institute said yesterday that the use of monoclonal antibody to carry toxins to search and destroy cancer cells, without harming normal ones, is under way in more than 15 experimental studies involving a variety of cancers. He predicted that within the next few years there will "undoubtedly be another wave" of successful cancer therapies using monoclonal antibodies.