Hemophilia is a genetic disease that prevents blood from clotting properly leading to prolonged internal and external bleeding. Learn how gene therapy works to slow or stop disease progression by instructing cells to produce the missing clotting factor, along with information on approved therapies and clinical trials.
HEMGENIX is an FDA-approved gene therapy for the treatment of adults with hemophilia B (congenital Factor IX deficiency).
ROCTAVIAN is an FDA-approved gene therapy for the treatment of adults with severe hemophilia A (congenital factor VIII deficiency).
About Hemophilia
Hemophilia is a genetic disease that prevents blood from clotting properly leading to prolonged internal and external bleeding. Clotting factors are proteins in blood that help the body stop bleeds. Without the ability to effectively stop bleeding, a simple cut or bruise can lead to external bleeds, and internal bleeding inside joints and muscles can damage organs including the brain. There are 12 different clotting factors, commonly referred to as factors I through XII. The most common types of the disease are hemophilia A and hemophilia B.
Hemophilia A is caused by a gene variant that leads to a deficiency (not enough) of clotting factor VIII.
Hemophilia B is caused by a gene variant that leads to a deficiency (not enough) of clotting factor IX.
Gene Therapy Approach
Gene therapy aims to be given one time with the goal of eliminating the need for recurring treatments. Gene therapy for hemophilia A or hemophilia B would deliver a working copy of the faulty gene into the liver cells with instructions to produce the missing clotting factor. The gene with its new instructions is delivered to the cells using a viral vector. Vectors are often derived from viruses because viruses have evolved to be good at getting into cells. But the viral genes are removed so only therapeutic (good) genes are delivered.
The liver has a variety of jobs in our body, and one of them is to create different elements in our blood—including clotting factors VIII and IX. By delivering the vector with the working gene into liver cells, the cells is given instructions to produce stable amounts of clotting factors to control bleeds. Gene therapy has been shown to reduce the rate of annual bleeds with hopes of improving the quality of life for people living with the disease.
Researchers are also exploring the use of gene editing to correct clotting factor production. Gene editing goes directly inside the cell to edit pieces of DNA using technology that is highly precise to make this change.
FDA-Approved Gene Therapies
HEMGENIX is an AAV-based gene therapy given one-time for the treatment of adults with Hemophilia B (congenital Factor IX deficiency) who:
- Currently use Factor IX prophylaxis therapy, or
- Have current or historical life-threatening hemorrhage, or
- Have repeated, serious spontaneous bleeding episodes.
ROCTAVIAN an AAV-based gene therapy given one-time for the treatment of adults with severe Hemophilia A (congenital factor VIII deficiency) who:
It is important to inform your primary medical provider or hematologist to understand if a gene therapy is the best option for you and to understand health insurance coverage, along with short- and long-term risks. For instance, gene therapy can be an alteration for the lifetime, so people should be aware that there could be long term effects (both good and bad) that are not known at this time.
Other treatment options
These include infusions, medications, physical therapy, or surgery to repair tissue damage. The most common option is the infusion to administer clotting factor replacements directly into the bloodstream. These treatments are required throughout a person’s entire lifetime to prevent or treat bleeding. Visit the hemophilia treatment centers page from CDC for more information.
Treatment Pipeline
Gene therapy for different types of hemophilia are being investigated in clinic trials and preclinical studies. Clinical trials are a required part of the research process that help scientists understand the way a drug or treatment will interact with the human body and whether it is safe and effective. Preclinical studies are an even earlier stage of research that test the safety and effectiveness of a treatment in animal or cell-based models before proceeding with a human clinical trial. Clinical trials may differ on various aspects of their design. Speak with a trusted provider or member of the clinical trial research team if you are considering participating in a clinical trial.
To stay up to date on open clinical trials in the U.S. or globally, visit the ASGCT Clinical Trials Finder and search using the "diagnosis" filter.
Participating in a Clinical Trial
It is important to be well informed when deciding to participate in a clinical trial. Below are some key points to consider. Visit the considering a clinical trial page for more information and resources to help guide you.
- Eligibility - Eligibility for a trial is based on strict inclusion and exclusion criteria. These are specific factors that determine whether a person can or cannot enroll in a clinical trial. This is an important way for researchers to understand if the gene therapy is working properly and to ensure participant safety. For hemophilia a key factor is age. Since the liver grows with us from childhood to adulthood, gene therapy trials are currently only being conducted in eligible adults with hemophilia. If a child was given the treatment, the therapy’s beneficial effects could become weaker as their liver grows with age. Other criteria may include factors such as how advanced the disease is, or previous use of treatments. Speak with a healthcare provider or a member of the clinical trial research team to help determine if you may be eligible for a clinical trial.
- Risks - As with any medical intervention, there are risks that need to be carefully considered. Before participating in a clinical trial, a member of the research team should review any potential risks and benefits with the patient or caregiver. Therapies being studied in clinical trials are not a guaranteed cure and cannot guarantee beneficial results. There is always a chance that the investigational treatment may not work. In the event a person is not satisfied with the outcome, the person may not receive another dose of the gene therapy. In addition, participating in a clinical trial may prevent future participation in other trials or from receiving other types of treatments. Gene therapy can be an alteration for the lifetime, so people should be aware that there could be long term effects (both good or bad) that are not known at this time.
- Benefits - Participating in a trial may offer many potential benefits compared to not receiving any form of intervention for a fatal disease. Gene therapy aims to be a one-time treatment with lasting positive effects that slow or stop disease progression for a lifetime. However, there is no guarantee. If gene therapy is received earlier in the course of disease, it has the potential to stop damage before it occurs.
- Long-term follow up - It is the patient’s responsibility to comply with the long-term follow-up of a trial. The Food and Drug Administration (FDA) guidelines require the clinical trial research team to monitor safety and potential long-term effects of a gene therapy. Follow up may require in-person appointments that vary in frequency and location, or completion of mailed packets with response forms. The need for long-term data collection for a gene therapy trial can last up to 15 years—another reason to consider all outcomes and responsibilities that come with committing to a clinical trial. There are a limited number of participants in trials so a lack of attendance at follow-up appointments leads to not enough study data. This could negatively affect FDA approval of a new therapy and thereby limit access to the therapy by patients who did not participate in the clinical trial.
Access
At this time, we do not know if or when more gene therapies will be approved by the FDA and commercially available for people living with different types of hemophilia. The overall process may take several more years, until it is deemed safe and effective by the FDA or regulatory agencies in other countries.
Stay Informed
A number of organizations provide individuals with blood disorders, and their families, with resources, research updates, and support: