A single treatment with gene therapy, an experimental technique for fixing faulty genes, has been shown to boost output of a vital blood clotting factor, possibly offering a long-term solution for people with hemophilia B.
Researchers said the same technology was also being studied as a treatment for hemophilia A, the far more common type of the inherited bleeding disorder.
It is a technique for potentially permanently curing patients, said Dr. Charles Abrams, American Society of Hematology secretary and associate chief of hematology/oncology at the University of Pennsylvania in Philadelphia.
Both safety and efficacy have held back the field of gene therapy. One experiment cured two French boys with a rare immune disorder but gave them leukemia in 2002, and an Arizona teenager died in a 1999 gene therapy experiment.
The approach used by researchers at the University College London Cancer Institute and St. Jude Children's Research Hospital in Memphis, Tennessee, involved the use of a novel viral vector, designed to target the liver specifically.
The strategy involves replacing the defective gene that causes the bleeding disorder with a correct version delivered via the virus to the patient's liver cells - the only cells in the body capable of producing certain clotting factors missing or deficient in people with hemophilia.
The factors are numbered using Roman numerals. The two main forms of the disease are hemophilia A, caused by a lack of clotting factor VIII, and hemophilia B, caused by a lack of clotting factor IX.
Researchers have so far treated six men with severe hemophilia B who were producing clotting factor IX at less than 1 percent of normal levels. The general goal of current treatment with recombinant factor IX is to achieve factor levels greater than 1 percent of normal.
Four of the six trial participants have stopped routine treatment and remain free of spontaneous bleeding. The other two have increased the interval between factor infusions to once every 10 days to two weeks from two to three times a week, said Dr. Andrew Davidoff, chairman of the department of surgery at St. Jude's and co-author of the study.
HIGH COST FOR CURRENT TREATMENT
Frequent treatments with manufactured factor IX, known as recombinant factor concentrates, can cost hundreds of thousands of dollars a year, making hemophilia a tempting target for gene therapy.
The trial is truly a landmark study, Dr. Katherine Ponder, hematology and oncology professor at Washington University in St. Louis, said in a New England Journal of Medicine editorial.
If further studies determine that this approach is safe, it may replace the cumbersome and expensive protein therapy currently used for patients with hemophilia B, she wrote.
The trial results were published in the NEJM and reported on Saturday at a meeting of the American Society of Hematology in San Diego.
The six trial subjects were broken into three groups with each group receiving a different concentration of new genes.
Factor IX levels in the first subject have remained at 2 percent for nearly two years, while the two patients treated with the highest dose have seen FIX levels rise to between 3 and 12 percent, researchers said.
One high-dose subject developed elevated levels of transaminases, an indicator of possible liver damage, and another had a slight increase in liver enzymes. Both cases were resolved with steroids, the researchers said.
Plans are to treat more patients with the highest dose used so far, and if research continues to succeed, the treatment could be widely available in the next five years or so, said Dr. Amit Nathwani, co-lead study author of the Department of Hematology at UCL Cancer Institute in London.
He also said the team was working to use the technique for treating hemophilia A.
ISI Group analyst Mark Schoenebaum said the gene therapy could pose big competition for companies such as Biogen Idec that are producing recombinant factor concentrates.
This clearly presents a curveball to our (and much of Wall Street's) assumptions around the future of the hemophilia market, he said in an email to investors.
The analyst said estimated sales of the hemophilia factors accounted for between $10 and $17 of his $125 price target for shares of Biogen, which closed at $112.95 on Friday.
People with hemophilia bleed more following trauma than people without the disease, and those with severe disease may bleed spontaneously. Since the gene is carried on the X chromosome, hemophilia is almost exclusively a disease of men.
But women can pass the gene to their offspring.
Hemophilia has often been called the Royal Disease since it was carried by Britain's Queen Victoria and affected many of the royal families of Europe.
Hemophilia B is much less common than hemophilia A. About one in five hemophilia patients has hemophilia B, according to the National Institutes of Health.
The global market for Factor VIII products is about $5 billion, while the market for Factor IX is worth about $1 billion.
Worldwide, about one in 5,000 men is born with hemophilia A and 1 in 25,000 men is born with hemophilia B each year.