Where couldHemophiliatreatmentBe going next?

Discover what may be on the horizon for your patients with hemophilia.

The content of this site is intended to provide US healthcare professionals with information about gene therapy research.

We want to hear your thoughts
about gene therapy.

What Is Gene Therapy?

Genetic medicine, which uses genetic material in the treatment or prevention of disease, is being studied across various therapeutic areas.1,2 Some examples of genetic medicine include gene therapy ,* gene editing, and gene regulation.1-3

This website focuses on gene therapy.



Gene therapy introduces a functional gene (also called a working gene) into a person's body. The functional gene provides the body with the information that is needed to produce the missing or nonfunctional protein.4

*Gene therapy may also be called gene transfer or gene addition.

Why Gene Therapy for Hemophilia?

Hemophilia may be a disease particularly suitable for gene therapy—because it's caused by a variation in a single gene. The transfer of a functional gene enables the production of the missing or nonfunctioning Factor VIII and Factor IX.5-8

And gene therapy may be beneficial in some hemophilia patients—because even a small increase in circulating levels of Factor VIII or Factor IX may modify the bleeding phenotype. The delivery of a functional gene to a patient, and the expression of the missing factor to even some degree, may have the potential for sustained therapeutic effect and modification of the patient's bleeding phenotype.5-7


Gene therapy has been studied for over 20 years in hemophilia A and hemophilia B—and for more than 50 years across a variety of medical conditions.9-11

In the case of gene transfer technology for hemophilia, the delivery of the functional gene provides the information needed for the body to produce whichever clotting factor protein is missing—either Factor VIII or Factor IX.5 People treated with gene therapy may still pass on genetic variations and conditions to their children.12,13

Research is continuing today and multiple clinical trials are ongoing.14

The Goal of 
Gene Therapy in Hemophilia

—To achieve steady-state factor levels through a "one-time" infusion15,16

Keeping factor expression within the therapeutic window is believed to reduce a patient's vulnerability to spontaneous bleeds. This is important because bleeding is associated with joint damage and other complications.17-19

Steady-state factor levels: Factor replacement requires recurrent dosing, which can produce peaks and troughs in circulating factor levels.8,14,17,19  The potential for bleeding and breakthrough bleeding increases as patients approach low trough levels.17


Gene therapy is being evaluated for its potential to provide therapeutic steady-state factor levels.14,15 The goal of gene therapy for hemophilia is to generate clotting factor within the therapeutic window and above sub-therapeutic zone (bleeding risk), over an extended period of time.14,15


Graphs are for illustrative purposes only.

One-time infusion: Research is ongoing to investigate whether gene therapy can achieve its therapeutic goals with one-time dosing. Gene therapy may help some people with hemophilia A or B manage their disease without the need for frequent infusions or injections.15,16

How Gene Therapy Is Delivered

Gene therapy involves the delivery of a gene (called a transgene) to a specific target tissue or organ.20 In most current gene therapy research for hemophilia A and B, the functional gene is carried by a viral capsid.21,22  The delivery of the functional copy of the gene may allow for one-time dosing.15,16,21


Why AAV vectors in hemophilia gene therapy? 

While adenovirus, retrovirus, and lentivirus vectors are being evaluated, adeno-associated virus (AAV) vectors are used in most gene therapy studies in hemophilia today. Scientists modify the AAV when inserting the transgene; therefore, the AAVs used in gene therapy are formally referred to as recombinant AAV (rAAV).9,16

AAVs are nonpathogenic16

AAVs are nonpathogenic in natural form, amenable to gene therapy treatment.16 AAVs were first used in clinical trials over 25 years ago, and there is a growing body of evidence to support their use in gene therapy for hemophilia.9,16

Over time, some people are naturally exposed to AAVs, which may generate an immune response that produces neutralizing antibodies (NAbs). The presence of NAbs in some people with hemophilia may impact their eligibility for gene therapy.19,21

Why target the liver?

The liver is central to understanding and treating hemophilia, and there are several reasons for it being the primary target tissue for gene therapy. The liver plays a vital role in human metabolism and detoxification, and, in addition, the synthesis of Factor VIII (primarily by hepatic sinusoidal endothelial cells) and Factor IX (solely by hepatocytes).20,22

Gene Therapy Clinical Considerations 


Current clinical trials use various entry criteria to identify eligible patients. Some of the considerations determining eligibility are detailed below, although each clinical trial is different.22 Additional considerations may emerge as continued research informs the efficacy, safety, and durability of gene therapy for hemophilia.23

In addition to formal eligibility criteria, patients may need support in weighing their decision as they consider gene therapy and committing to this new treatment process.24


Variability and Nonresponders 

Clinical trials have shown variability in efficacy following gene therapy, including, in some cases, no clinical response. Research is ongoing to better understand the variability in patient response both initially and longer term.6,14,25

Durability/Duration of Effect 

Clinical trials are investigating duration of expression of FVIII and FIX. Animal and emerging human data have shown that durability of therapeutic effect following certain rAAV-based gene therapies varies, with some maintained for 10 years or more.26

Long-term follow-up (eg, 15 years) is suggested after treatment with gene therapy for hemophilia A and B to monitor safety and duration of factor expression.27

Scientists are researching the potential to re-dose gene therapy. Generally, exposure to the AAV vector results in the formation of neutralizing antibodies (NAbs), which likely impacts future dosing.28

Gene Therapy Clinical Considerations 


Current clinical trials use various entry criteria to identify eligible patients. Some of the considerations determining eligibility are detailed below, although each clinical trial is different.22 Additional considerations may emerge as continued research informs the efficacy, safety, and durability of gene therapy for hemophilia.23

Questions About Gene Therapy
in Hemophilia?

You and your patients may have questions about gene therapy in hemophilia. While more information will become available over time, the following points may help provide some initial answers or clarification.

Who is eligible for gene therapy?

Treatment with gene therapy is not appropriate for all patients with hemophilia. For example, at present, pediatric patients, patients with anti-AAV neutralizing antibodies (NAbs) above a certain threshold, and patients with potential liver issues or other diseases may not be eligible.22 At this time, gene transfer research in hemophilia has only focused on patients with moderately severe or severe hemophilia A and B.30

What might be important to discuss with my patients?

Your role in enabling shared decision-making will remain critical to empower patients to make the best decisions for themselves. It will be important to discuss the unique aspects of this treatment with your appropriate patients including eligibility for gene therapy, safety considerations, post-infusion follow-up requirements including long-term monitoring, and more.

If a patient might be appropriate and eligible for gene therapy, what other requirements do they need to understand?

Patients should understand that gene therapy will come with some responsibility following the infusion, including short- and long-term monitoring and lifestyle changes that may be required after treatment.35

Can gene therapy be re-dosed?

As part of the humoral immune response, neutralizing antibodies (NAbs) may develop following single administration of gene therapy. As a result, this could impact the potential for re-administration.23,30,36

Research is currently ongoing to learn more about the immune response and potential strategies to overcome this for re-dosing. Most current gene therapy trials exclude patients who have already received gene therapy.

The choice to undergo treatment with gene therapy is an important one.

When the time comes, you and your patient can work together to determine which, if any, option is best.

Download these questions to help you have an informed discussion with your patients.


Pfizer Has Been Committed to Innovation in Hemophilia for Over 25 Years. 

Currently, we’re working to unlock the potential of new research for patients living with
hemophilia A and B worldwide.

Thank you!

Your form has been submitted. A member of our team will be in contact shortly regarding your enquiry.