30 trials of gene therapy are suspended by FDA

Second case of leukemia in similar French study raises questions, alarms

January 15, 2003|By Thomas H. Maugh II | Thomas H. Maugh II,SPECIAL TO THE SUN

The Food and Drug Administration suspended 30 gene therapy trials yesterday - half of those under way in the United States - after learning that a second French child had developed leukemia after receiving the promising, yet highly experimental, treatment.

The agency had halted three trials in October after the revelation that a child had developed the potentially fatal form of cancer. The suspension was broadened to include an additional 27 trials yesterday "because of unanswered questions about what is going on," said Dr. Philip Noguchi, who is in charge of gene therapy issues at the FDA.

But Noguchi cautioned that participants in the programs should not be unduly alarmed because an intensive study has revealed no cases of leukemia outside the French program.

Dr. Donald Kohn, who leads a trial halted at Children's Hospital Los Angeles, said the "clinical hold" was appropriate.

"We need to find out why this has happened twice," he said.

An emergency meeting has been called for Friday by the Office of Biotechnology Activities at the National Institutes of Health to discuss the problem. The FDA has also scheduled a meeting Feb. 28 at which some of the trials could be reinstated.

The suspension of trials represents another black mark for a field in which researchers have been widely criticized for promising more than they have been able to deliver and for rushing into clinical trials before most potential problems have been worked out.

The biggest was the 1999 death of Jesse Gelsinger, 18, who suffered a violent reaction to a gene therapy treatment. "I have no doubt that the death of Jesse Gelsinger is going to lead to nothing but a cautious, go-slow approach," said ethicist Arthur Caplan of the University of Pennsylvania. "As a society, we're more nervous about genetics" than about any other form of medical therapy, he said.

Kohn said that, despite the new setback, he remained hopeful for the field. "We have to remember that seven of the 10 kids [in the French trial] were cured of an otherwise fatal disease" without developing problems, he said. "There is tremendous promise in gene therapy, but this specific approach may be a problem and we may need to look for other ways to use gene therapy in this disease."

Gene therapy seeks to replace defective genes with healthy genes to reverse genetic disorders. Researchers believe it is the only potential treatment for many inherited diseases.

The two children who developed leukemia were among 11 infants with a disease, known as X-linked severe combined immune deficiency (X-SCID), treated with gene therapy by Dr. Alain Fischer and his colleagues at the Necker Hospital for Children in Paris.

The illness is commonly known as "bubble boy" disease.

The children have a defective gene, called GammaC, which prevents them from developing immunity against infectious diseases. Untreated, such children die within the first year of their lives from severe and recurrent infections. Some victims are successfully treated with a bone marrow transplant from a sibling who is a perfect match, but such matches are not often available.

Fischer used a so-called retrovirus to insert a healthy copy of the gene into the children's hematopoietic (blood-forming) cells. His trial was widely hailed because nine of the 11 children apparently were cured of their disease and were able to go home. But in October, one of the children, now 3, was found to have leukemia. Leukemia has a 90 percent cure rate with chemotherapy, and the child is reportedly doing well under treatment.

But U.S. officials concluded that the leukemia was a direct result of the gene therapy, and they halted three U.S. trials that had very similar protocols. Those included two trials at Children's Hospital. Kohn said researchers there voluntarily suspended a third trial - involving treatment for pediatric AIDS - that had not yet begun.

Now that a second leukemia case has been discovered, FDA halted all trials in which retroviruses are being used to insert genes into hematopoietic cells.

The American Society of Gene Therapy said yesterday that it will organize an ad hoc committee to review such trials to learn whether the leukemia is unique to the French trial or a more common problem.

Thomas H. Maugh II is a reporter for the Los Angeles Times, a Tribune Publishing newspaper.

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