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​University of Pittsburgh Medical Center Performs First In Vivo Gene Therapy for Hemophilia A

PITTSBURGH, June 3, 1999 — On June 1, 1999, a 50-year-old man with hemophilia A received the first in vivo gene therapy for this disease as part of a phase I clinical trial performed at the University of Pittsburgh Medical Center (UPMC). The trial, designed and initiated through Chiron Corp., uses Chiron’s gene therapy introducing the blood-clotting protein known as factor VIII. The therapy offers promise for the tens of thousands of men affected with this disease worldwide.

"We are very excited to participate in this study, which could permanently restore the ability to produce the clotting factor deficient in men with hemophilia A," stated Margaret V. Ragni, M.D., professor of medicine at the University of Pittsburgh, director of the Hemophilia Treatment Center of Western Pennsylvania and recent member of the Medical and Scientific Advisory Committee of the National Hemophilia Foundation. "This therapy has the potential to reduce the costs and complications associated with this debilitating condition."

This small-scale, phase I trial is designed primarily to ensure the safety of the therapy and to determine the best dose of the factor VIII gene to deliver. Physicians also will measure the expression of the factor VIII gene in treated patients. Patients will be monitored closely for one year after treatment for safety and duration of factor VIII response. Subsequently, they will be enrolled in a long-term surveillance registry.

Hemophilia A is a bleeding disorder that is transmitted genetically so that it affects only males. Approximately 1 in 10,000 men has the disorder. Affected individuals carry a defect in the gene for the factor VIII protein, which helps to clot blood. As a consequence, they cannot produce functional factor VIII and frequently may suffer bleeding episodes, some of which are life threatening. These episodes often occur in joints or other body cavities. Recurrent bleeding into joints may lead to chronic arthritis and pain. Although patients infuse the factor VIII protein to prevent such episodes, this prophylactic therapy is costly and difficult to administer. Moreover, hemophiliacs may develop antibodies to the factor VIII protein. The in vivo gene therapy, by contrast, offers a real possibility of a long-term treatment for the disease by supplying a functional copy of the factor VIII gene to the body.

"Our hope is that this in vivo therapy will produce enough factor VIII protein to protect patients from spontaneous recurrent bleeding and thereby avoid some of the chronic disabilities associated with the disease," added Dr. Ragni.

"In preclinical models, we achieved continuous long-term production of circulating factor VIII. We are now initiating testing in humans; an important milestone for Chiron," said Lewis (Rusty) T. Williams, Ph.D., M.D., Chiron’s chief scientific officer and president of its research and development group.

The hemophilia in vivo gene therapy employs a retrovirus that has been modified so that it cannot replicate. Such replication-defective viruses have been used extensively in trials of clinical gene therapies for a variety of diseases. The gene for factor VIII is placed inside this vector, which patients receive directly as an infusion. This approach differs considerably from a recently initiated trial of ex vivo gene therapy for hemophilia A, in which cells are taken from a patient, grown in culture, genetically modified and returned to the patient. Ex vivo gene therapies take longer to perform and must be tailored to each patient.

Once inside the body, scientists believe that the in vivo-introduced retrovirus delivers its genetic payload principally to the liver and spleen. Researchers expect that the factor VIII gene will permanently integrate into a cell’s genetic material and, in effect, becomes a drug-production factory. Normally, the liver manufactures the factor VIII protein.

The first protocol patient was treated at the UPMC’s General Clinical Research Center, a federally supported unit with special capabilities to carry out complex protocols, including gene therapies and treatments with biological response modifiers.

Chiron Corp., headquartered in Emeryville, Cal., is a leading biotechnology company that participates in three global healthcare markets: biopharmaceuticals, blood testing and vaccines. For more information, visit the company’s website at


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