The Food and Drug Administration yesterday approved the powerful new drug cyclosporin, a substance many medical experts believe will revolutionize the practice of organ transplant medicine.
Cyclosporin suppresses the body's immune system, slowing or preventing the rejection of new organs--the greatest cause of death among transplant patients. In use as an experimental drug since 1979, it has almost doubled the success rate of kidney and liver transplants in clinical trials, according to the FDA.
Arthur Hull Hayes Jr., approving cyclosporin yesterday, his last day as food and drug commissioner, noted that the agency had processed 123 volumes of data in order to approve the drug in nine months, in contrast to the two years or so the process once took. Hayes, who resigned to become dean of New York Medical College in Valhalla, N.Y., has worked during his tenure to speed up the process of drug approvals.
The field of transplant medicine has undergone a dramatic revival since cyclosporin was released for limited clinical trials in 1979.
"Medical centers all over the world are re-entering the field," Stanford University's Dr. Norman E. Shumway said in recent congressional testimony. He told members of a House Science and Technology subcommittee that the number of transplants in 1983 "should at least double last year's total, with further expansion expected later in the decade."
"Since we began the use of cyclosporin at Stanford in December, 1980, there has not been a single instance of a clinically diagnosable rejection," Shumway said. Another prominent surgeon, Dr. G. Melville Williams of Johns Hopkins University, said the field of transplant medicine has been "excited and restless awaiting the availability of cyclosporin."
In the years that followed the first heart transplant operation 15 years ago by the South African surgeon Dr. Christiaan Barnard, the problem of rejection kept survival rates very low and eventually dissuaded most centers from attempting cardiac transplants.
But since the introduction of cyclosporin, one-year survival rates in clinical studies have doubled, to almost 80 percent, the transplant centers report. Unlike some other drugs used to prevent the body from rejecting a transplant, cyclosporin does not destroy the bone marrow, the FDA said yesterday.
The story of this promising new agent began in 1969, when researchers from Sandoz Ltd. in Basel, Switzerland, isolated a novel molecule from a previously unknown strain of soil fungus found during a routine test for biological activity in soil samples collected in Norway and the United States.
But the drug's unexpected potential was nearly lost when it was shelved temporarily after disappointing results in tests designed to evaluate it for antibiotic or anti-cancer activity.
Through the persistence of Dr. Jean F. Borel, chief of immunology at Sandoz, cyclosporin's remarkable immuno-suppressive properties were discovered in January, 1972.
The drug showed a selective effect on the immune system, suggesting that it would slow the organ-rejection reaction while leaving undisturbed the body's ability to fight life-threatening infections that often complicate major surgery.
FDA spokesman William Grigg said that although the drug produces some adverse side effects, including tremors and hair growth, the FDA regards them as within the tolerance range, or else they disappear or decrease as the dosages of the drug are decreased after the transplant is in place.
Recipients must take maintenance doses of cyclosporin throughout their lives.
In an FDA expert committee convened earlier this year to consider the drug's safety and effectiveness, its approval was strongly recommended for liver, kidney, heart and pancreas transplant patients. Dr. Fitzhugh S.M. Mullan, of the FDA advisory committee, called it "an immense breakthrough."
One problem the committee encountered was the increasing unwillingness of transplant surgeons to conduct tests to compare groups of patients given cyclosporin with groups of patients denied the new drug.
"When they started turning people out of the hospital and out of the ICUs intensive care units in a third of the time they had done previously, there was no question whatsoever, they weren't going back to the other therapy," said Dr. David Winter, a clinical researcher with Sandoz. The firm plans to market the drug under the trade name Sandimmune.
A maintenance dosage of the drug will cost about $4,000 a year, according to Sandoz, but the company expects the cost to come down as production is increased and surgeons drop the dosage as they become more familiar with the drug.
Cyclosporin's approval is cause for concern among major health insurers facing the prospect of paying for the growing number of extremely costly transplant operations. Only kidney and cornea transplants now qualify for health insurance, but cyclosporin's availability may soon make heart, lung and liver grafts safe enough to justify their reclassification as insurable surgical procedures.
Blue Cross-Blue Shield, the nation's largest health insurer, posed the questions insurers face in a recent issue of the journal Perspectives. Statistics show that hundreds of thousands of Americans are candidates for the "miracle cure" offered by organ transplants, the authors say.
"Are the few added years of life per patient worth the commitment of medical skills and other resources?" they ask. "And who's going to pay the giant price tags--averaging maybe $50,000 a crack?" Other estimates of transplant costs for major organs approach $500,000.