New gene therapy could transform lives of patients with rare bleeding disorder

New research carried out at the Royal Free Hospital and supported by CRN North Thames shows that a single gene therapy injection could dramatically reduce the bleeding risk faced by people with haemophilia B.

The research, published in the New England Journal of Medicine, looked at how effective a new type of gene therapy, called FLT180a, was in treating severe and moderately severe cases of haemophilia B.

Haemophilia B is a rare and inherited genetic bleeding disorder caused by low levels of the factor IX (FIX) protein, needed for forming blood clots that help prevent or stop bleeding. The gene responsible for making FIX protein is located on the X chromosome, so the severe form of haemophilia B is much more common in men.

Currently, patients with haemophilia B need to inject themselves regularly – usually weekly – with something known as recombinant FIX to prevent excessive bleeding. However, despite advances in treatment, patients continue to see debilitating joint damage caused by their haemophilia when using this type of therapy.

The clinical trial found that one-time treatment with the FLT180a gene therapy led to sustained production of the FIX protein in the majority of patients, so they no longer needed the regular injections.

Out of 17 patients aged 18 or over who underwent screening, ten with severe or moderately severe haemophilia B took part in the 26-week trial of FLT180a. They are also all enrolled in the long-term follow up study to assess other factors including safety for 15 years.

The study was a collaboration between the Royal Free London, UCL and biotechnology company Freeline.

Lead author Professor Pratima Chowdary, clinical lead for haemophilia within the rare disease centre 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.”

This type of gene 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. This new gene can then generate the missing FIX proteins which allows the blood to clot as normal.

In nine out of the ten patients, the treatment led to a sustained increase in FIX protein production, which led to a decrease in excessive bleeding. They also no longer required weekly injections of the FIX protein.

After 26 weeks, five patients had normal levels of FIX protein, three had low but increased levels, and one patient treated at the highest dose had an abnormally high level.

Participants had to take immune suppression drugs over several weeks to several months, to prevent their immune systems from rejecting the therapy.

While the immune supperssion drugs were generally well tolerated, all patients experienced some form of adverse event, with an abnormal blood clot in one who received the highest FLT180a dose and had the highest levels of FIX protein.

Freeline co-founder Amit Nathwani, consultant at the Royal Free London and professor of haemotology at UCL, who co-authored the study, said: “Gene therapy is still a young field that pushes the boundaries of science for people with severe genetic diseases.

“The B-AMAZE long-term data add to the growing body of evidence that gene therapy has the potential to free patients from the challenges of having to adhere to lifelong therapy or could provide treatment where none exists today.”

Pamela Foulds, MD, chief medical officer of Freeline, said: “These results continue to support our confidence that a single dose of FLT180a could free people with hemophilia B from bleeding and the need for lifelong FIX replacement through durable expression of FIX at protective levels.”

The trial was designed by UCL and Freeline Therapeutics and supported by Freeline Therapeutics.