Brian O’Mahony
Chief Executive, Irish Haemophilia Society
The long-cherished hope of seeing gene therapy and a possible functional cure for haemophilia is now visible on the horizon.
A person with haemophilia B has a deficiency in coagulation Factor IX. In normal individuals without haemophilia, the Factor IX level is typically between 50% and 150%. In severe haemophilia, it is usually less than 1%.
Gene therapy involves an intravenous infusion of a modified human Factor IX gene, carried within an attenuated virus known as an adeno associated virus (AAV). This delivery system is known as a vector. AAV virus does not cause illness. In this case it is acting as a delivery system for the FIX gene. The vector travels to the liver where the FIX gene is released, and these liver cells then start producing factor IX.
Three individuals undergoing clinical trials
On World Haemophilia Day in April 2019, the Irish Haemophilia Society highlighted the fact that clinical trials of gene therapy for both haemophilia A and haemophilia B (the rarer form) were underway globally. We are working with the haemophilia clinicians to provide the opportunity for some people with haemophilia in Ireland to participate in some of these clinical trials.
The long-cherished hope of seeing gene therapy and a possible functional cure for haemophilia is now visible on the horizon.
In March this year, we announced that the first Irish person with haemophilia B had been treated with gene therapy as part of a clinical trial. Since then, the number of people treated has been increased to three. All three individuals are reported to be doing well.
Findings so far
In the earlier dose finding study, FIX levels six months post infusion ranged from 33% to 57%. This changed the individual from having severe haemophilia to mild haemophilia or even normal. It is also our hope that people with haemophilia in Ireland will have an opportunity to participate in Factor VIII Gene Therapy clinical trials (for haemophilia A) in 2021.
Gene therapy could be licenced in the near future
Gene therapy for haemophilia has been on the horizon for over 20 years. It is now close to becoming a licenced therapy. It is anticipated that the first Factor VIII gene therapy will be licenced later this year and the first Factor IX gene therapy will be licenced in 2021.
When licenced, these therapies will initially be options only for adults with severe haemophilia. (As the liver in a child continues to develop, there is significant turnover of liver cells so the current gene therapies in clinical trials would not be suitable for children as the liver cells producing the factor would be lost as the child’s liver cells changed).
A functional cure for haemophilia?
The current therapies in clinical trials are also one-off therapies as the person will develop antibodies to the AAV, thereby preventing retreatment. Work is ongoing to allow retreatment in the future. For most of the clinical trials, individuals with pre-existing AAV antibodies are also excluded. The Factor IX trial here is an exception as, with this particular vector, those with pre-existing antibodies can be included without damaging the effectiveness.
Questions remain regarding the range of factor expression we will see and the duration of expression, but the long-cherished hope of seeing gene therapy and a possible functional cure for haemophilia is now visible on the horizon.