A clinical trial shows that the treatment prevented the risk of excessive bleeding in nine of the 17 patients treated
A single injection of a gene therapy could dramatically reduce the bleeding risk faced by people with a type of hemophilia B.
It is a clinical trial carried out on 10 patients whose results are published today in “The New England Journal of Medicine”, in which researchers from the University College of London-UCL, the Royal Free Hospital and the biotechnology company Freeline Therapeutics tested a new type of adeno-associated virus (AAV) gene therapy candidate, called FLT180a, to treat severe and moderately severe cases of hemophilia B.
Hemophilia B is a rare, inherited genetic bleeding disorder caused by low levels of the factor IX (FIX) protein, which is necessary for the formation of blood clots that help prevent or stop bleeding. The gene responsible for the production of the FIX protein is located on the X chromosome, which is why the severe form of hemophilia B is much more common in men..
Currently, hemophilia B patients must be injected regularly – usually weekly – with recombinant FIX, ie regular replacement therapy to prevent excessive bleeding. Despite advances in treatment, patients can continue to experience joint damage.
This multicentre phase I/II clinical trial, called B-AMAZE, and the related long-term follow-up study, found that single treatment with FLT180a led to sustained production of the FIX protein from the liver in nine out of ten patients , through four different dosage levels, eliminating the need for regular replacement therapy.
Eliminating the need for hemophilia patients to regularly inject their missing protein is an important step in improving their quality of life
Pratima Chowdary
Royal Free Hospital
Of the 17 male patients aged 18 years and older who were screened, 10 with severe or moderately severe hemophilia B participated in the 26-week trial of FLT180a. All of them are also enrolled in the long-term follow-up study to assess the safety and durability of FIX expression for 15 years.
“Eliminating the need for hemophilia patients to regularly inject their missing protein is an important step in improving their quality of life,” said lead author Pratima Chowdary.
AAV gene therapy works by using an envelope of proteins found on the outer shell of the virus, to deliver a working copy of a gene directly to a patient’s tissues to make up for one that isn’t working properly. The newly synthesized proteins are released into the blood, and a single infusion can achieve long-lasting effects.
The patients had to take immunosuppressive drugs for several weeks or months to prevent their immune systems from rejecting the therapy, and all reported known side effects.
Although the treatment was generally well tolerated, all patients experienced some type of adverse effect, with an abnormal blood clot in one who received the highest dose of FLT180a and had the highest levels of FIX protein.
«Long-term data from B-AMAZE add to evidence that gene therapy has the potential to free patients from lifelong therapy or could provide treatment where none exists today», says Freeline co-founder Professor Amit Nathwani.
In nine of the ten patients, the treatment led to a sustained increase in the production of the FIX protein, which led to a decrease in excessive bleeding. In addition, they no longer needed weekly injections of protein FIX.
After 26 weeks, five patients had normal FIX protein levels, three low but increased levels, and one patient treated with the highest dose had an abnormally high level.
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