Haemophilia B is a rare genetic disorder caused by low levels of the factor IX (FIX) protein, which is needed for forming blood clots to prevent or stop bleeding.
Currently, patients need to inject themselves regularly with a ‘recombinant FIX’ to prevent excessive bleeding. Despite advances in treatment, patients continue to experience joint damage caused by haemophilia when using this type of therapy.
New research from Royal Free Hospital in London, published in the New England Journal of Medicine, examined the effectiveness of a new type of gene therapy called FLT180a when treating severe and moderately severe haemophilia B. The study was a collaboration between the Royal Free London, UCL and biotechnology company Freeline.
This therapy works by using a small part of a virus to deliver a copy of a gene directly to patient tissues, to compensate for one that is missing; the new gene can then generate the missing FIX proteins, allowing the blood to clot as normal.
The clinical trial found that one-time treatment with the FLT180a gene therapy led to sustained production of the FIX protein in nine out of the ten patients, which led to a decrease in excessive bleeding and meant that they no longer required weekly injections. After 26 weeks, five patients displayed normal levels of FIX protein, three had low but increased levels, and the patient who had been treated with the highest dose had an abnormally high level of the protein.
All participants had to take immune suppression drugs over several weeks to months to prevent their immune systems from rejecting the therapy; whilst they were generally well tolerated, all patients experienced some form of adverse event in response to the drugs.
The ten patients who took part in the 26-week trial have enrolled in a 15 year follow-up study to access other factors such as long-term safety.
Lead author Professor Pratima Chowdary, Clinical Lead for Haemophilia at the Royal Free London, said: “Removing the need for haemophilia patients to regularly inject themselves with the replacement protein is an important step in improving their quality of life. In the ongoing follow-up study, we are working to understand the most efficient dosing level of FLT180a and how we can modify our approach to immune suppression.”
The trial was designed by UCL and Freeline Therapeutics and supported by Freeline Therapeutics.