Hemgenix

What Is Hemgenix and What Is It Used For?

Hemgenix is a gene therapy medicine that delivers a working copy of the factor IX gene to liver cells, enabling the body to produce its own clotting factor and reduce or eliminate bleeding episodes in adults with hemophilia B.

Hemgenix (etranacogene dezaparvovec) represents a transformative approach to treating hemophilia B, a rare inherited bleeding disorder caused by deficiency or dysfunction of coagulation factor IX. Unlike traditional factor IX replacement therapy, which requires regular intravenous infusions throughout a patient's life, Hemgenix aims to provide a long-term or potentially curative solution through a single administration.

Hemophilia B affects approximately 1 in 25,000 to 30,000 male births worldwide, according to the World Federation of Hemophilia (WFH). People with this condition are born with a mutation in the F9 gene, which encodes the factor IX protein essential for normal blood clotting. Without adequate factor IX levels, patients experience a tendency toward prolonged bleeding, spontaneous joint and muscle bleeds, and potentially life-threatening haemorrhages following trauma or surgery.

How Hemgenix Works

The active substance in Hemgenix is based on an adeno-associated virus serotype 5 (AAV5) that has been modified so it cannot replicate or cause disease in humans. This engineered virus serves as a delivery vehicle (vector) carrying a functional copy of the human F9 gene — specifically the high-activity Padua variant — directly to hepatocytes (liver cells).

Once inside the liver cells, the factor IX-Padua transgene is expressed from extrachromosomal (episomal) DNA, meaning it largely remains outside the cell's chromosomes. The transduced liver cells then begin producing functional factor IX protein, which is secreted into the bloodstream. As circulating factor IX levels rise, the blood's ability to clot improves, reducing the frequency and severity of bleeding episodes.

Clinical trial results from the HOPE-B study demonstrated that a single infusion of Hemgenix led to a significant and sustained increase in factor IX activity levels, with a mean activity of approximately 36–39% of normal at 18 months post-infusion. This level is well above the 5% threshold that distinguishes mild hemophilia from moderate/severe disease, and many patients were able to discontinue routine prophylactic factor IX infusions entirely.

Approved Indications

Hemgenix is approved for the treatment of severe and moderately severe hemophilia B (congenital factor IX deficiency) in adult patients who do not currently have, and have not previously had, inhibitors (neutralising antibodies) against the factor IX protein. It received conditional marketing authorisation from the European Medicines Agency (EMA) in February 2023 and was approved by the United States Food and Drug Administration (FDA) in November 2022.

What Should You Know Before Receiving Hemgenix?

Before receiving Hemgenix, your doctor will assess your eligibility through antibody testing, liver function evaluation, and a thorough review of your medical history. Several conditions may prevent you from being a candidate for this gene therapy.

Contraindications

Hemgenix must not be given in the following situations:

• Hypersensitivity: Known allergy to etranacogene dezaparvovec or any of the excipients (sucrose, polysorbate 20, potassium chloride, potassium dihydrogen phosphate, sodium chloride, sodium hydrogen phosphate, hydrochloric acid, water for injections).
• Active infection: Any ongoing acute infection or chronic infection that is not adequately controlled with medication.
• Severe liver disease: The presence of advanced liver fibrosis (significant scarring and thickening) or cirrhosis (chronic liver scarring), as the liver cells targeted by the vector may not function properly.

Warnings and Precautions

Pre-Treatment Assessments

Your physician will conduct several evaluations before determining whether Hemgenix is appropriate for you:

• Anti-AAV5 antibody testing: Blood tests may be performed to measure the level of pre-existing antibodies against the AAV5 vector used in Hemgenix. High levels of these antibodies could reduce the effectiveness of the therapy.
• Liver function tests: Blood tests to check liver enzyme levels, ultrasound imaging of the liver, and elastography (a specialised scan to detect scarring or fibrosis) will be performed to confirm the liver is healthy enough for treatment.
• Factor IX inhibitor screening: Blood tests to confirm the absence of neutralising antibodies against factor IX protein.

During and After Infusion

Hemgenix is administered in a hospital setting under close medical supervision. Infusion-related reactions — including allergic responses, flushing, chest discomfort, and dizziness — can occur during or shortly after the infusion. Your medical team will monitor you during the infusion and for at least 3 hours afterwards. If reactions occur, the infusion rate may be slowed or temporarily paused, and corticosteroids may be given to manage symptoms.

Liver Enzyme Monitoring

One of the most common effects following Hemgenix infusion is an immune-mediated rise in liver transaminases (ALT and AST), known as transaminitis. This occurs because the immune system recognises the AAV5 vector in the liver cells. To manage this:

• Weekly blood tests are required for at least the first 3 months after infusion.
• If liver enzymes rise, more frequent testing and corticosteroid treatment may be necessary.
• Testing continues every 3 months from month 4 through year 1, then every 6 months in year 2, and annually for at least 5 years.

Thromboembolic Risk

After Hemgenix treatment, factor IX levels may temporarily rise above normal ranges in some patients. Abnormally elevated factor IX can theoretically increase the risk of blood clots (venous or arterial thrombosis, pulmonary embolism). This risk is considered low due to the underlying coagulation system deficiency, but patients with cardiovascular risk factors (prior heart disease, atherosclerosis, hypertension, diabetes, or age over 50) should be monitored carefully.

Avoiding Blood and Tissue Donation

After receiving Hemgenix, you must not donate blood, semen, organs, tissues, or cells for transplantation. The active substance may temporarily be shed through blood, semen, breast milk, and other bodily fluids, and these restrictions help prevent unintended exposure of non-hemophilia B individuals to the gene therapy vector.

Future Gene Therapy

After Hemgenix administration, the immune system produces antibodies against the AAV5 vector. It is currently unknown whether treatment with Hemgenix can be repeated or whether treatment with a different gene therapy product would be feasible in the future.

Pregnancy and Breastfeeding

There are no data on the use of Hemgenix in pregnant or breastfeeding women. Hemgenix is not recommended for women of childbearing potential as the effects on pregnancy and the foetus are unknown. The treatment should not be used during pregnancy or breastfeeding.

After a male patient receives Hemgenix, effective contraception (such as barrier methods including condoms) must be used by the patient and any female partner of childbearing potential for 12 months following treatment. This precaution addresses the theoretical risk that the factor IX gene from the father's Hemgenix treatment could be transferred to the child with unknown consequences. Male patients must also not donate semen during this period.

Drug Interactions

Patients taking hepatotoxic medications (drugs known to be harmful to the liver) should discuss with their doctor whether to discontinue such treatments before receiving Hemgenix, as concurrent hepatotoxic therapy could worsen the liver enzyme elevations expected after gene therapy administration.

How Is Hemgenix Administered?

Hemgenix is given as a single, one-time intravenous infusion at a dose of 2×10¹³ genome copies per kilogram of body weight. The infusion is performed in a hospital under specialist supervision and typically takes 1 to 2 hours.

Administration

Children and Adolescents

Hemgenix has not been studied in patients under 18 years of age. No dosing recommendations can be made for paediatric patients. The growing liver in children presents a theoretical challenge, as cell division could dilute the episomal transgene copies over time, potentially reducing the durability of treatment effect.

After the Infusion

Following Hemgenix infusion, it may take several weeks before factor IX levels begin to rise sufficiently to provide meaningful bleeding protection. During this transitional period:

• You may need to continue your existing factor IX replacement therapy.
• Your doctor will check your factor IX activity levels weekly for at least the first 3 months.
• The decision on when to reduce or stop factor IX replacement therapy will be made based on your individual factor IX levels and clinical response.
• You and your doctor should develop a treatment plan for managing potential bleeding episodes during surgery, trauma, or other high-risk situations.

Driving and Using Machines

Hemgenix may have a minor effect on the ability to drive and use machines. Temporary dizziness, fatigue, and headache have been reported shortly after infusion. If you experience these symptoms, avoid driving or operating machinery until you are sure Hemgenix is not affecting your ability to do so safely.

What Are the Side Effects of Hemgenix?

The most commonly reported side effects of Hemgenix include headache, elevated liver enzymes (ALT and AST), flu-like symptoms, elevated C-reactive protein, and infusion-related reactions. Most side effects are manageable with monitoring and, where necessary, corticosteroid therapy.

Like all medicines, Hemgenix can cause side effects, although not everyone experiences them. The following side effects have been reported in clinical trials with Hemgenix. If you experience any severe or persistent symptoms after receiving Hemgenix, contact your healthcare provider immediately.

Infusion-Related Reactions

Infusion-related reactions are among the most frequently reported adverse events and can occur during or shortly after the Hemgenix infusion. These reactions may include allergic symptoms (hypersensitivity), flushing, chest discomfort, dizziness, eye itching, urticaria (hives), upper abdominal pain, and fever. Your medical team is prepared to manage these reactions by adjusting the infusion rate, pausing the infusion, or administering medications such as corticosteroids.

Liver Enzyme Elevations

Transaminitis (elevated ALT and AST) is an expected immune-mediated response following Hemgenix administration. The immune system reacts to the AAV5 vector in liver cells, causing inflammation. This typically occurs within the first few weeks to months after infusion and is managed with close monitoring and, when necessary, corticosteroid therapy. It is crucial to attend all scheduled blood tests so that any liver enzyme changes can be detected and treated promptly.

How Should Hemgenix Be Stored?

Hemgenix must be stored refrigerated at 2°C–8°C (36°F–46°F), protected from light, and must not be frozen. After dilution, the prepared solution can be stored at 15°C–25°C for up to 24 hours.

Hemgenix is handled exclusively by healthcare professionals in hospital settings, and patients will not typically need to store the product themselves. However, understanding the storage requirements helps ensure treatment quality and safety:

• Temperature: Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze.
• Light protection: Keep in the original packaging to protect from light.
• After dilution: The diluted solution in the infusion bag can be stored at 15°C–25°C (59°F–77°F), protected from light, for up to 24 hours after dose preparation.
• Inspection: Do not use if you notice particles, cloudiness, or discoloration in the solution.
• Shelf life: Use before the expiry date printed on the label and carton after "EXP".

Keep out of the sight and reach of children. This medicinal product contains genetically modified organisms (GMOs). Personal protective equipment including gloves, safety glasses, protective clothing, and a face mask should be worn during preparation and administration.

What Does Hemgenix Contain?

Each millilitre of Hemgenix contains 1×10¹³ genome copies of etranacogene dezaparvovec as the active substance, along with excipients including sucrose, polysorbate 20, and buffering salts in water for injections.

Active Substance

The active substance is etranacogene dezaparvovec, a recombinant adeno-associated virus serotype 5 (AAV5) vector carrying the human coagulation factor IX Padua variant gene. Each mL contains 1×10¹³ genome copies (gc).

Excipients (Inactive Ingredients)

• Sucrose
• Polysorbate 20
• Potassium chloride
• Potassium dihydrogen phosphate
• Sodium chloride
• Sodium hydrogen phosphate
• Hydrochloric acid (for pH adjustment)
• Water for injections

Appearance and Packaging

Hemgenix is a clear, colourless concentrate for solution for infusion, supplied in vials containing 10 mL each. The total number of vials per package is tailored to the individual patient's dosing needs based on body weight and is specified on the packaging. This medicinal product contains genetically modified organisms.

Frequently Asked Questions About Hemgenix