Gene Therapy Hemophilia

The New York Times

May 28, 2004

Company Discontinues Trial of Hemophilia Gene Therapy

By ANDREW POLLACK

In what might be another blow to the field of gene therapy, a small biotechnology company is discontinuing its closely watched attempt to treat hemophilia, apparently because its trial ran into technical and safety problems.

The company, Avigen, said yesterday that it was ending the hemophilia trial so it could shift its strategic focus to neurological diseases. But it also said that the hemophilia therapy faced "certain scientific, regulatory and clinical hurdles."

Dr. Mark A. Kay, a professor at Stanford who was helping conduct the trial, said some safety issues had arisen. He said he had been asked by Avigen not to discuss them until the company conducts a conference call with investors this morning.

"There hasn't been anything really severe in regards to patients getting sick or what have you, but there are some safety hurdles that will have to be overcome," Dr. Kay said. "There are things in the human trial that weren't predicted in animal studies."

The hemophilia trial was closely watched because the treatment showed some hints of working, which could have made it one of the first successful gene therapies. Dogs have been essentially cured of hemophilia using the approach, and Bayer licensed the rights to Avigen's treatment.

Gene therapy generally has not worked, and there have been recent safety problems. In France last year and the year before, two infants who were cured of a rare immune disorder by gene therapy subsequently developed leukemia linked to the treatment. And in 1999, a teenager died while undergoing gene therapy at the University of Pennsylvania.

Hemophiliacs lack certain proteins needed for blood to clot. Avigen was trying to give patients the gene to allow them to produce Factor IX, the blood-clotting protein lacked by people with hemophilia B, the less common of the two forms of the disease.

Gene therapy often uses genetically engineered viruses to carry the desired gene into patients' cells. The type of virus used by Avigen, known as an adeno-associated virus, is increasingly used in gene therapy because it is supposed to be safer than the type of virus used in the trial in which the teenager died. So if Avigen's issues relate to the virus itself, it could mean problems for much of the gene therapy field.

But Avigen said it thought the problems were "specific to hemophilia." Dr. Kay said he was not sure whether the problems were related to the virus. But he said that "all of these issues are solvable" and that he had "no doubt" that gene therapy for hemophilia could be made to work.

The trial had run into several safety issues and delays previously. Indeed, after several years the trial was still in Phase 1, the first of three stages, and only a handful of patients had been treated.

The slow progress apparently contributed to a corporate refocusing. The longtime chief executive, John Monahan, resigned, apparently under pressure, in March, and was replaced in that post by the chief operating officer, Kenneth Chahine.

Avigen's stock, which has been dropping steadily for more than three months, fell 3 cents yesterday, to $3.90. The company's announcement was made after the close of trading.


	May 28, 2004 Company Discontinues Trial of Hemophilia Gene Therapy By ANDREW POLLACK In what might be another blow to the field of gene therapy, a small biotechnology company is discontinuing its closely watched attempt to treat hemophilia, apparently because its trial ran into technical and safety problems. The company, Avigen, said yesterday that it was ending the hemophilia trial so it could shift its strategic focus to neurological diseases. But it also said that the hemophilia therapy faced "certain scientific, regulatory and clinical hurdles." Dr. Mark A. Kay, a professor at Stanford who was helping conduct the trial, said some safety issues had arisen. He said he had been asked by Avigen not to discuss them until the company conducts a conference call with investors this morning. "There hasn't been anything really severe in regards to patients getting sick or what have you, but there are some safety hurdles that will have to be overcome," Dr. Kay said. "There are things in the human trial that weren't predicted in animal studies." The hemophilia trial was closely watched because the treatment showed some hints of working, which could have made it one of the first successful gene therapies. Dogs have been essentially cured of hemophilia using the approach, and Bayer licensed the rights to Avigen's treatment. Gene therapy generally has not worked, and there have been recent safety problems. In France last year and the year before, two infants who were cured of a rare immune disorder by gene therapy subsequently developed leukemia linked to the treatment. And in 1999, a teenager died while undergoing gene therapy at the University of Pennsylvania. Hemophiliacs lack certain proteins needed for blood to clot. Avigen was trying to give patients the gene to allow them to produce Factor IX, the blood-clotting protein lacked by people with hemophilia B, the less common of the two forms of the disease. Gene therapy often uses genetically engineered viruses to carry the desired gene into patients' cells. The type of virus used by Avigen, known as an adeno-associated virus, is increasingly used in gene therapy because it is supposed to be safer than the type of virus used in the trial in which the teenager died. So if Avigen's issues relate to the virus itself, it could mean problems for much of the gene therapy field. But Avigen said it thought the problems were "specific to hemophilia." Dr. Kay said he was not sure whether the problems were related to the virus. But he said that "all of these issues are solvable" and that he had "no doubt" that gene therapy for hemophilia could be made to work. The trial had run into several safety issues and delays previously. Indeed, after several years the trial was still in Phase 1, the first of three stages, and only a handful of patients had been treated. The slow progress apparently contributed to a corporate refocusing. The longtime chief executive, John Monahan, resigned, apparently under pressure, in March, and was replaced in that post by the chief operating officer, Kenneth Chahine. Avigen's stock, which has been dropping steadily for more than three months, fell 3 cents yesterday, to $3.90. The company's announcement was made after the close of trading.
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