Source: Reuters
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 haemophilia B.
Researchers said the same technology was also being studied as a treatment for haemophilia 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 Haematology secretary and associate chief of haematology / 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 leukaemia 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 haemophilia.
The factors are numbered using Roman numerals. The two main forms of the disease are haemophilia A, caused by a lack of clotting factor VIII, and haemophilia B, caused by a lack of clotting factor IX.
Researchers have so far treated six men with severe haemophilia B who were producing clotting factor IX at less than 1 per cent of normal levels. The general goal of current treatment with recombinant factor IX is to achieve factor levels greater than 1 per cent 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 haemophilia a tempting target for gene therapy.
The trial “is truly a landmark study,” Dr Katherine Ponder, haematology and oncology professor at Washington University in St Louis, said in a New England Journal of Medicine (NEJM) editorial.
“If further studies determine that this approach is safe, it may replace the cumbersome and expensive protein therapy currently used for patients with haemophilia B,” she wrote.
The trial results were published in the NEJM and reported on Saturday at a meeting of the American Society of Haematology 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 per cent for nearly two years, while the two patients treated with the highest dose have seen Factor IX levels rise to between 3 and 12 per cent, 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 Haematology at UCL Cancer Institute in London.
He also said the team was working to use the technique for treating haemophilia 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.
People with haemophilia 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, haemophilia is almost exclusively a disease of men.
But women can pass the gene to their offspring.
Haemophilia 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.
Haemophilia B is much less common than haemophilia A. About one in five haemophilia patients has haemophilia B, according to the National Institutes of Health.
The global market for Factor VIII products is about US$5 billion, while the market for Factor IX is worth about US$1 billion.
Worldwide, about one in 5,000 men is born with haemophilia A and one in 25,000 men is born with haemophilia B each year.
