An Update on Gene Therapy for Hemophilia

Answers to common questions about this potentially game-changing treatment.

After several decades of research, gene therapy for hemophilia is moving closer to becoming a reality. One of the most sought-after treatments for hemophilia, this one-time treatment may potentially increase a person’s factor levels to normal or close to normal, which would enable them to avoid needing factor infusions for a long period of time. Read on for answers to commonly asked questions about gene therapy for hemophilia.

What is gene therapy?

Gene therapy is a treatment that involves modifying a person’s genes in order to treat or cure a disease. Different methods of gene therapy include:

  • Gene transfer, which involves putting genetic information into a vector, or carrier, which then carries the working copy of a gene to a person’s cells
  • Gene editing, which involves removing or correcting pieces of DNA within the gene rather than replacing the gene
  • Cell therapy, which involves removing cells from the patient’s body, introducing a new gene or correcting a faulty gene in the cell, and then putting the modified cells back into the body.

How is gene therapy used to treat hemophilia?

Most of the gene therapies being investigated for the treatment of hemophilia are done using gene transfer. Hemophilia A and B are caused by a single gene mutation. The gene therapy inserts a functional version of the defective gene—the factor VIII gene in hemophilia A or the factor IX gene in hemophilia B—into the liver, which triggers clotting factor production. The vector used to transport the healthy gene to cells in the liver is called an adeno-associated virus (AAV), which is a non-disease-causing virus, modified as a delivery vehicle, and given as an intravenous injection. AAV is a popular choice because it especially targets the liver, which is where the clotting factor proteins are made.

What is the status of gene therapies being studied for the treatment of hemophilia?

Currently, there are several gene therapy treatments for hemophilia A and B being studied in clinical trials to determine how well they work and how safe they are.

One of the drugs that is furthest along in the pipeline is valoctocogene roxaparvovec, an investigational gene therapy for the treatment of adults with severe hemophilia A. The manufacturers of this gene therapy announced in January 2022 that they expect to apply for approval to the Food and Drug Administration (FDA) in the second quarter of 2022, which would be followed by a six-month review by the FDA.

Another investigational gene therapy for hemophilia that’s in the later stages of development is AMT-061 (etranacogene dezaparvovec), which is being studied in patients with severe to moderately severe hemophilia B. In December 2021, the drug manufacturers announced favorable results of a phase 3 clinical trial, and said they planned to submit regulatory applications for marketing approval in the first half of 2022.

To learn about other gene therapies for hemophilia currently under investigation, go to ClinicalTrials.gov and type “hemophilia” in the text box labeled “condition or disease,” and “gene therapy” in the box labeled “other terms.”

Who can take part in a clinical trial for gene therapy?

In general, individuals who are eligible to participate in gene therapy clinical trials for hemophilia are males 18 and older who:

  • Have severe hemophilia A or B (factor levels of less than 1%) without inhibitors
  • Have no evidence of hepatitis and if they have HIV, it must be under good control
  • Have no evidence of liver dysfunction (such as abnormal liver enzymes or abnormal liver biopsy)
  • Have no detectable neutralizing antibodies against the vector
  • Are otherwise healthy (no diabetes, history of cancer, heart disease, glaucoma, high blood pressure, etc.)

Why aren’t children with hemophilia eligible for gene therapy clinical trials?

The reason that gene therapy for hemophilia is not available for people under 18 is that this therapy targets the liver cells, and children’s livers continue to grow until at least their early teens. As a person’s liver grows, the effect of gene therapy may diminish.  Researchers say that in the future, as they learn more about gene therapy safety, there may be opportunities for children to enroll in studies.

What are the risks involved with gene therapy for hemophilia?

One of the biggest risks is that there’s no guarantee that it will work, and if it doesn’t work, you won’t get another chance using the same or similar vector. In addition, it isn’t clear how long the effects of the gene therapy may last.

Other risks include a strong immune system reaction, the possibility that the vector would travel to other cells in the body outside the liver, and the possibility that the liver would produce too much clotting protein. 

If you’re thinking of enrolling in a clinical trial or you’re interested in undergoing gene therapy once it is available on the market, discuss your options and concerns with your healthcare team.

Source: HemAware, National Hemophilia Foundation