FDA Approves First Gene Therapy To Treat Adults With Hemophilia B

Hemophilia is the most common blood disorder diagnosed around the world — so why don’t we have a cure?

Hemophilia is a very serious condition that can even be life-threatening. It reduces the blood’s ability to clot, which can lead to excessive bleeding even after a minor injury.

The condition is equally distributed across all ethnic groups worldwide. An estimated one in 10,000 newborn babies will be diagnosed with hemophilia, and over 400,000 people worldwide are currently living with the condition.¹

Despite its prevalence, we still don’t have a definitive cure for hemophilia. Instead, modern treatment options are usually centered around symptom management. People with hemophilia often use infusible clotting factor medications to reduce their risk of developing a potentially life-threatening bleed.

Fortunately, with recent research and success in clinical trials, a new treatment option has been approved that may change how hemophilia is managed.

Approved in November 2022, Hemgenix is the first gene therapy treatment shown to be clinically successful in managing symptoms and reducing the incidence of bleeding in people with hemophilia B.² This is the first medication of its kind to be approved for managing hemophilia, and researchers ran groundbreaking clinical trials to receive that approval.

So what is Hemgenix, and how can gene therapy help people with hemophilia? Read on to learn more.

What is hemophilia?

Before we explore the clinical trials that led to the first gene therapy for hemophilia being approved by the US Food and Drug Administration (FDA), we first need to understand the condition’s common identifying traits, symptoms, and causes.

Hemophilia is categorized as a rare disorder. As a health condition that impacts the blood’s natural clotting function, people with hemophilia are at an increased risk of experiencing bleeding after a minor injury. Bleeding can even occur spontaneously. It can be very difficult to stop bleeding once it starts.

The condition is often passed from parent to child via their genes, but it can occur spontaneously in rare cases.

There are two primary types of hemophilia:³

• Hemophilia A — Also known as classic hemophilia or factor VIII deficiency, hemophilia A is the most common form of the condition. On average, one in over 5,600 male births in the US will be affected by hemophilia A.⁴

• Hemophilia B — Often referred to as Christmas disease or factor IX deficiency, hemophilia B is a less common form of the condition. According to current estimates, hemophilia B occurs in one in every 25,000 births worldwide and affects roughly 6,000 individuals across the US.⁵ ⁶

Understanding how hemophilia is passed on

Most people diagnosed with hemophilia have inherited the disorder from their parents via their genetics.

Every person has two sex chromosomes — either XX or XY. They inherit one chromosome from each parent. A male child receives his X chromosome from his mother and his Y chromosome from his father. A female child receives one X chromosome from each parent.

A male only has one X chromosome. If he has a faulty copy of a gene on the X chromosome, then he’ll display the characteristics associated with that faulty gene. A female has a second X chromosome, so she may receive a normal copy of the same gene from her other parent. This often protects females from diseases that are carried on the X chromosome — like hemophilia.

The faulty gene that results in hemophilia is located on the X chromosome, meaning that in most cases, hemophilia is passed from mother (with XX chromosomes) to son (with XY chromosomes).⁷

Females carrying the faulty gene are usually protected from hemophilia by their second X chromosome. These people are considered “carriers” of the condition.

It’s still possible for carriers to experience mild to moderate symptoms of hemophilia because the normal gene on the other X chromosome may not entirely make up for the faulty one. Female carriers can pass the faulty gene on to their children.

Females are not completely protected from hemophilia. They will exhibit symptoms of the condition if they inherit two X chromosomes that both have the faulty gene. In fact, current estimates show that 11% of people with hemophilia across the US are women.⁸

Interestingly, inheriting the faulty gene for hemophilia is not the only way you can develop the condition. In some cases, the fault in the gene may arise spontaneously when a cell makes an error in copying DNA. This means that some people who have this genetic condition have not inherited it from their parents and are the first in their family to develop it.

It’s also possible for a person to develop hemophilia later in life as a result of immune system dysfunction. This is known as autoimmune hemophilia, which is extremely rare. It occurs when the immune system targets and destroys the functioning clotting factors in a person’s body.⁹

Signs and symptoms of hemophilia

As a health condition that impacts the blood’s clotting function, hemophilia symptoms can develop throughout the body. The condition affects every organ, tissue, and cell connected to the vascular system.

Symptoms can range in severity from mild to life-threatening. Examples of some of the most common symptoms of hemophilia A and B include:¹⁰

• Bleeding into joints — It’s common for blood to seep into the spaces in an affected person’s joints as a result of a spontaneous bleed or trauma to the nearby tissues. This bleeding can cause joint pain, stiffness, and swelling. It can affect any joint but most commonly affects the ankles, knees, and elbows.

• Bruising easily — People with hemophilia may develop a bruise (a collection of blood under the skin) from even light contact. In more severe cases, any level of contact can cause a hematoma (a pool of blood in the soft tissue) to develop.

• Bleeding of the mouth and gums — Maintaining adequate oral hygiene can be a challenge for people living with hemophilia. Bleeding from the gums and mouth from minor procedures like flossing or brushing can be difficult to control. Bleeding during dental procedures (such as tooth extractions) can be severe, so people with hemophilia may require additional medical care in these circumstances.

• Frequent nosebleeds — Getting a nosebleed under control can be challenging, even for people without a bleeding disorder. People with hemophilia commonly experience prolonged nosebleeds that are sometimes severe enough to require emergency medical assistance.

• Blood in the urine or stool — If an internal bleed develops in the gastrointestinal or urinary tract, a person with hemophilia may see blood when they use the toilet.

• Prolonged bleeding from minor cuts and scrapes — Small cuts and scrapes may require significant intervention in people with hemophilia. It may take a lot of gauze or bandages and a prolonged period of strong pressure to control something as small as a paper cut.

• Difficulty physically recovering from surgery or traumatic events — If a person with hemophilia experiences trauma or needs to undergo surgery, the recovery period will likely be significantly longer than average. People with hemophilia often require extra care and longer hospital stays to ensure that bleeding can be controlled after any surgical procedure.

Existing treatments for hemophilia

Modern research has yet to find a definitive cure for hemophilia, so all available treatment options are intended for symptom management.

Symptom management is often achieved with synthetic or replacement clotting factors. These replace the missing or dysfunctional blood clotting factors to allow more normal clotting to occur.

Treatment depends on your specific type of hemophilia, your unique genetics, and your family history. Here are some examples of common hemophilia treatment options:¹¹

• Concentrated blood clotting products — Often referred to as clotting factors, these infusible medications can be made from donated human plasma (the liquid part of blood) or made synthetically in a lab. Concentrated factor VIII (FVIII) is used to treat hemophilia A, while concentrated factor IX (FIX) is used to treat hemophilia B. Multiple infusions may be needed each week to manage the condition, depending on the type of clotting factor used.

• Aminocaproic acid — Used as a short-term treatment to manage bleeding from minor surgical procedures, aminocaproic acid prevents the breakdown of any existing blood clots. In people with hemophilia, it’s often used for dental procedures because it inhibits a certain enzyme in the saliva that dissolves blood clots. This is not a replacement for clotting factors, but it can help strengthen the blood clots that form when you undergo a procedure.

• Non-factor replacement therapies — Other medications can also be used to manage hemophilia, including drugs that mimic clotting factor function and hormone replacements that slow the rate of bleeding. They may be used on their own or in conjunction with clotting factors, depending on your individual needs.

Unfortunately, just like any other treatment for a health condition, the options available to people with hemophilia are not without complications and drawbacks.

Over time, your body can develop “inhibitor” antibodies in response to the concentrated clotting factors you receive — a process that slowly makes you less responsive to these medications. This means that the treatment may stop working in the future, even if it has worked well for a period of time.

Unfortunately, this outcome is the norm for many people living with hemophilia — a situation that is both costly and stressful for everyone involved. So, when the FDA approved a new gene therapy treatment option for hemophilia B in November 2022, the news about its potential benefits caught many people’s attention.

The latest FDA-approved hemophilia treatment looks promising (but comes with a hefty price tag)

Hemgenix is a gene therapy medication that has been FDA-approved for treating certain adults with hemophilia B. The medication’s scientific name is etranacogene dezaparvovec-drlb, while Hemgenix is the brand name.

As a gene therapy, Hemgenix acts on a person’s DNA to cause a malfunctioning gene to change. This particular medication uses AAV5, a modified virus, to initiate change to the malfunctioning gene that causes hemophilia B. The virus is used to deliver a functional copy of the gene for factor IX into the body’s cells, and some of these cells will integrate the gene and begin expressing it.

After a single dose of Hemgenix, cells within the body are capable of producing clotting factor IX at a rate 5–8 times greater than before.¹²

The drug is currently approved only for those who already use intravenous concentrated FIX with a history of current or previous serious bleeding events.¹³ This means that its safety and efficacy have been clinically proven when treating hemophilia B in this group.

In stark contrast to other hemophilia medications, which often need to be administered multiple times per week to be effective, Hemgenix requires just one dose. However, it currently costs $3.5 million for a single dose of this therapy.

What did we learn from the clinical trials?

To gain FDA approval, Hemgenix had to go through a series of expensive clinical trials to determine its safety and efficacy.¹⁴ The drug was tested as part of the HOPE-B trial, the largest gene therapy clinical trial for hemophilia B on record. Two clinical trials were conducted on 57 adult men aged 18–75 living with moderate to severe hemophilia B.

In one study, factor IX production in participants who had received Hemgenix changed significantly. As a result, 94% of the men who had received Hemgenix were able to reduce or stop their concentrated FIX dosages and reported a 54% decrease in annual bleeds.

Possible side effects of Hemgenix include signs of liver damage as well as headaches and flu-like symptoms.

Overall, the findings are very promising. Study participants also reported feeling less fearful because, for many people living with hemophilia B, spontaneous bleeds can strike at almost any time and can be incredibly serious.

The lowdown

With a price tag of $3.5 million per infusion, Hemgenix may seem incredibly expensive. However, it appears that this is the first step into gene therapy for treating hemophilia, and it may be the future of managing the disease.

Gene therapy offers many benefits to people with hemophilia, including increased peace of mind, less time spent receiving care, and proven long-term efficacy and safety. This new FDA-approved medication is already changing the lives of many patients and families affected by hemophilia.

More clinical research and studies are needed for researchers to learn more about other potential gene therapy options. This is the first step into the future of care and is already paving the way for other new (and hopefully more affordable) treatment options for people with hemophilia.

This breakthrough could also open the door for effective gene therapy for other genetic conditions.

References:

1. Hemophilia (2023)

2. FDA approves first gene therapy to treat adults with hemophilia B | U.S. Food and Drug Administration

3. Hemophilia | NIH: MedlinePlus

4. Hemophilia A | The National Hemophilia Foundation

5. Hemophilia B — Affected populations | The National Organization for Rare Disorders

6. Clinical, humanistic, and economic burden of severe hemophilia B in the United States: Results from the CHESS US and CHESS US+ population surveys (2021)

7. What is hemophilia? | Centers for Disease Control and Prevention (CDC)

8. Women can have hemophilia, too | Centers for Disease Control and Prevention (CDC)

9. Acquired hemophilia | The National Organization for Rare Disorders

10. What is hemophilia? | Centers for Disease Control and Prevention (CDC)

11. Current treatments | The National Hemophilia Foundation

12. U.S. food and drug administration approves CSL’s HEMGENIX® (etranacogene dezaparvovec-drlb), the first gene therapy for hemophilia B | CSL

13. FDA approves first gene therapy to treat adults with hemophilia B | U.S. Food and Drug Administration

14. (As above)

Claire Bonneau is a medical writer and certified trauma operating room nurse.