This gene therapy reduces bleeding in hemophiliacs

A single injection of gene therapy could significantly reduce the risk of bleeding faced by people with hemophilia type B.

This is a clinical trial carried out on 10 patients, the results of which are published today in “The New England Journal of Medicinein which researchers from the University College London-UCLthe Free Royal Hospital and 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 factor IX (FIX) protein, which is needed to form blood clots that help prevent or stop bleeding. The gene responsible for producing 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, patients with hemophilia B must receive regular – usually weekly – injections of recombinant FIX, i.e. regular replacement therapy to prevent excessive bleeding. Despite advances in treatment, patients may continue to experience joint damage.

This multicenter Phase I/II clinical trial, called B-AMAZE, and the related long-term follow-up study, revealed that a single treatment with FLT180a resulted in sustained production of the protein FIX from the liver in nine patients out of ten, by four different dosage levels, eliminating the need for regular replacement therapy.

Of the 17 male patients aged 18 and older who were screened, 10 with severe or moderately severe hemophilia B participated in the 26-week trial of FLT180a. All 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 envelope of the virus, to deliver a working copy of a gene directly into a patient’s tissues to compensate for the malfunctioning one. The newly synthesized proteins are released into the blood and a single infusion can have 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 side effect, with an abnormal blood clot in the one who received the highest dose of FLT180a and who had the highest levels of the protein FIX.

“Long-term data from B-AMAZE adds to evidence that gene therapy has the potential to free patients from lifelong therapy or could provide treatment where none exists todaysays Freeline co-founder Professor Amit Nathwani.

In nine of the ten patients, the treatment resulted in a sustained increase in the production of the protein FIX, which led to a decrease in excessive bleeding. In addition, they no longer needed weekly injections of FIX protein.

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.