Reducing bleeding risk for haemophilia B patients with gene therapy

Reducing bleeding risk for haemophilia B patients with gene therapy
© iStock/Edwin Tan

Scientists have developed a single gene therapy injection that could reduce bleeding risk in haemophilia B patients.

Scientists from University College London (UCL), Royal Free Hospital and biotechnology company Freeline Therapeutics collaborated to trial a new type of adeno-associated virus (AAV) gene therapy candidate called FLT180a to treat severe to moderately severe cases of haemophilia B.

The paper was published in the New England Journal of Medicine.

What is haemophilia B?

Haemophilia B is a rare clotting disorder caused by missing or defective factor IX, a clotting protein. People with haemophilia B bleed longer than people without the condition, which can occur internally, in joints and muscles, or externally from cuts, trauma, or dental procedures.

Currently, patients with haemophilia B inject themselves regularly with recombinant FIX, a regular replacement therapy that prevents excessive bleeding. Despite continued innovation in treatment options, patients still suffer from the effects of their condition, including joint damage.

Introducing a new gene therapy

The experts carried out a Phase I/II multi-centre clinical trial called B-AMAZE and a follow-up study to trial the AAV gene therapy. AAV gene therapy uses packaging from the proteins found in the virus’s outer coat, delivering a functional version of a gene directly into the patient tissues. Newly synthesised proteins are released into the blood, and the infusion achieves long-lasting effects.

Ten male patients aged 18 and over with severe or moderately severe haemophilia B partook in the 26-week trial of FLT180a and the long-term follow-up study, assessing the safety and durability of FIX expression for 15 years.

Lead author Professor Pratima Chowdary (Royal Free Hospital, UCL Cancer Institute) said: “Removing the need for haemophilia patients to regularly inject themselves with the missing protein is an important step in improving their quality of life. The long-term follow-up study will monitor the patients for the durability of expression and surveillance for late effects.”

The researchers found the treatment was generally tolerated; however, all participants experienced a form of adverse events and one participant experienced an abnormal blood clot and received the highest dose of FLT180a.

They found that the one-time treatment led to prolonged production of FIX protein from the liver in nine of ten patients across four different dose levels, reducing the need for regular replacement therapy. This treatment led to a decrease in excessive bleeding, and participants also no longer required weekly injections.

Pamela Foulds, MD, Chief Medical Officer of Freeline, said: “The B-AMAZE long-term data continue to support our confidence that a single dose of FLT180a could protect people with haemophilia B from bleeding and the need for lifelong FIX replacement through durable expression of FIX at protective levels.”



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