Most treatments for hemophilia primarily rely upon replacing proteins that patients lack in order to replenish them. The injected proteins normalize the levels of factor 8 or factor 9 for a period of time before they are broken down by the body. The therapy is very effective to prevent and stop bleeding and is used effectively by most people to manage their hemophilia. However, it does not make the disorder go away and is required all throughout the life of a person with hemophilia. Repeated injections and infusions have to be continued in order for levels to remain high enough to be effective. Gene therapy is a new way to treat hemophilia by providing a hemophiliac with a correct gene copy for their factor deficiency so that the body can make it on its own.
Scientists struggled to develop gene therapy treatments and overcame many hurdles. One of the hurdles, for example, was finding a way to deliver the gene to a person’s cells. Success was found through hijacking viruses, which naturally evolved to deliver genetic material to human cells. One such virus, Adeno-Associated Virus (AAV), a non-disease causing virus, has demonstrated the greatest success in delivering genes safely and effectively for hemophilia and in many other diseases as well. Much of the research in studying and developing the AAV for gene therapy occurred at the University of Florida.
Since 2024, gene therapies are available for Hemophilia A and Hemophilia B (Roctavian® and Hemgenix®, respectively). If a patient is interested and is able to receive it, gene therapy is given as a single infusion over the course of a day while they are monitored in a specialized clinic. Patients return home at the end of the day, but will continue to be monitored every week in the following months as we seek to establish the highest factor levels possible. Once factor levels have risen sufficiently and are stable, regular factor infusions can be stopped. At this point, patients move to a less frequent, but longer term, period of regular monitoring and follow-up. Most patients make factor at levels similar to a mild hemophiliac and are able to go many years without the need for regular factor injections. Because they still have mildly low levels, patients may still have the need for occasion factor infusions when faced with a very severe injury or high risk surgery. The factor levels are thought to decline over time and eventually most patients will require a return to prophylaxis to maintain the same bleeding control. The return to prophylaxis may be more than a decade for Hemophila A patients and 20-25 years for hemophilia B patients.
Gene therapy is not without its challenges despite all that has been achieved. It can only be given to those who are 18 years or older due to concerns about its longevity in younger patients. Some patients may not be able to receive it because of past exposure to the AAV virus. After it is delivered, the gene therapy cannot be given again due to this same immune response. It is an expensive infusion and may not be approved under their insurance plan. Others, despite receiving the infusion, may not express the gene and never produce factor. This has been associated with liver reactions and irritation, where the gene is delivered in hemophilia patients, and can often be controlled by suppressing the immune system using steroids. When started steroids may need to be given for many weeks or months. Patients are also required to abstain from alcohol to keep the liver as healthy as possible. Because this treatment is new, there may be effects that we are not aware of. The Hemostasis Treatment Center is committed to making gene therapy, as well as all other treatments for hemophilia, acessible and continue to improve it in the years to come.