Gene Therapy May Be Long-Term Cure for Type of Hemophilia

A new gene therapy appears to serve as a functional cure for the most common type of hemophilia, early clinical trial results indicate.

Patients who received the one-time intravenous therapy continue to have a more than 90% decrease in bleeding events two to three years after their initial treatment, researchers reported Jan. 1 in the New England Journal of Medicine.

The therapy fixes a broken gene in liver cells that causes production of flawed factor VIII, a protein that plays a key role in blood clotting.

People with this genetic mutation have hemophilia A, the most common type of this bleeding disorder. Hemophilia A accounts for 8 out of 10 cases of hemophilia, researchers said.

Hemophilia A patients must inject themselves with factor VIII every other day to prevent bleeding, said lead researcher John Pasi, a professor at Barts and The London School of Medicine and Dentistry in England.

"There's been a massive reduction in bleeding in the patients, and none of them any longer need to regularly treat themselves with factor VIII to prevent bleeding," Pasi said of participants in the phase 1/phase 2 clinical trial. "That huge treatment burden of having to give yourself an intravenous injection every other day has gone away."

The therapy uses a virus to carry the DNA sequence for a functional factor VIII gene into liver cells, he said.

"It infects liver cells and transfers into those cells the factor VIII gene," Pasi said. "Liver cells make factor VIII and then secrete it, and it passes into the circulation."

Seven initial participants in the study have a 96% decrease in bleeding events three years out, researchers report. Another six who joined later had a 92% decrease in bleeding by the end of year two.

"At three years, the patients who were treated at a higher dose were expressing functional levels of factor VIII -- somewhat lower than they were at their peak, but they're still at really good levels that are hugely effective in protecting the patients against bleeding," Pasi said.

A phase 3 trial involving more than 130 patients is underway, he said, and therapy manufacturer BioMarin Pharmaceutical has begun the application process with the U.S. Food and Drug Administration.

The most notable side effect is changes in liver enzymes with some patients, but those go away after treatment with steroids, Pasi said.

The treatment will not initially be available for every hemophilia A patient.

Because it involves infecting the liver with a virus, patients with hepatitis or HIV were kept out of the clinical trial, Pasi said. The treatment is only for adults now.

The biggest roadblock for some patients will be whether their bodies have developed an immune reaction to factor VIII, Pasi said.

About a third of patients with severe hemophilia develop antibodies to factor VIII, he said. Half of those cases resolve on their own, and the rest might need to be treated with immune tolerance protocols to get rid of the antibody.

Meg Bradbury, research director at the Hemophilia Federation of America, said the results are "extremely encouraging." But she noted that work needs to continue to find a cure for everyone with a bleeding disorder.

"This therapy and others like it may not be a one-size-fits-all for everyone," Bradbury said. "We still need to think about who is eligible for this particular therapy, who it will be effective for, and how we can help everyone in our community."

The therapy also is not likely to be cheap. Given that it will be a one-time treatment, its pricing will be different from that of a maintenance drug taken regularly, BioMarin representatives said.

They noted that the annual cost of therapy for a hemophilia A patient in the United States is around $500,000.

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