Hemophilia is a hereditary disease linked to the deficiency of a coagulation factor (factor VIII for hemophilia A, factor IX for hemophilia B). In the hemophiliac patient, the coagulation process is therefore compromised and if the patient does not bleed more, he bleeds longer. In some patients, recurrent bleeding into the joints can also lead to progressive joint damage and arthritis. If there is no definitive treatment for the disease, prophylactic treatments or in the event of a haemorrhagic accident, by intravenous injections of the failing coagulation factor, make it possible to prevent or stop the haemorrhage. Finally, the gene responsible for the production of coagulation factor IX being located on the X chromosome, severe forms of hemophilia B are much more frequent in men.
This novel adeno-associated virus (AAV) gene therapy, called FLT180a
opens up hope for patients to be able to do without regular and necessary injections of recombinant coagulation factor, which helps prevent excessive bleeding.
The B-AMAZE clinical trial multicenter phase I/II, carried out on 10 patients diagnosed with hemophilia B, confirms that a single injection of FLT180a leads to sustained production of coagulation factor by the liver in 9 out of 10 patients. Professor Pratima Chowdary of the UCL Cancer Institute comments on these good results: “Eliminating the need for haemophilia patients to regularly inject the missing protein is an important step in improving their quality of life”.
AAV gene therapy works by using the outer envelope of the virus, to deliver a working copy of a gene directly to the patient’s tissues to compensate for one that is not working properly. The synthesized proteins are released into the blood and a single infusion can induce lasting effects. However, patients must take immunosuppressive drugs for several weeks to several months to prevent their immune system from rejecting the therapy. The trial shows that while the treatment was generally well tolerated, all patients experienced some form of adverse event, with an abnormal blood clot in the one who received the highest dose of FLT180a and who had the levels the highest in clotting protein.
“Gene therapy remains a young but promising field for people with serious genetic diseases. These initial data from the B-AMAZE trial add to the growing body of evidence that gene therapy has the potential to free patients from lifelong therapies.”
The ongoing follow-up study should assess the durability of the therapeutic efficacy and monitor the occurrence of any longer-term side effects.
