Last updated Dec. 1, 2022, by Teresa Carvalho, MS
✅ Fact-checked by Joana Carvalho, PhD
What is Hemgenix for hemophilia?
Hemgenix (etranacogene dezaparvovec), formerly called AMT-061 or EtranaDez, is a gene therapy, given by infusion, to treat bleeding episodes in people with hemophilia B.
Originally developed by uniQure, the therapy’s global commercialization and licensing rights are now held by CSL Behring, following an agreement reached between the two companies in May 2021.
How does Hemgenix work?
Hemophilia B is caused by mutations in the F9 gene, which provides instructions to make clotting factor IX (FIX), a protein required for normal blood clotting. People with hemophilia B have either low levels of FIX or an abnormal version of the protein, both of which impair the clotting process and result in the bleeding disorder.
Hemgenix uses a modified and harmless adeno-associated virus 5 (AAV5) to deliver a highly functional copy of the F9 gene, called FIX-Padua, to patients’ liver cells. These are the body’s main producers of clotting factors.
The FIX-Padua gene version was shown to result in FIX clotting activity that’s 5–8 times greater than that normally associated with the F9 gene. As such, the therapy — given as a one-time infusion directly into the bloodstream (intravenously) — is expected to increase FIX levels, helping to prevent and control bleeds for long periods of time.
Who can take Hemgenix?
Hemgenix was approved by the U.S. Food and Drug Administration (FDA) in November 2022 to treat adults with hemophilia B who:
- are on prophylaxis, or preventive treatment.
- have (or have had) life-threatening bleeds.
- have had repeated, serious spontaneous bleeding episodes.
The gene therapy also is under regulatory review in Europe.
Hemgenix had been designated a breakthrough therapy in the U.S., a priority medicine (PRIME) in Europe, and an orphan drug in Australia. All of these designations are meant to accelerate development and regulatory review.
Who should not take Hemgenix?
According to the therapy’s prescribing information, there are no contraindications for its use. However, the therapy is not intended for use in women.
How is Hemgenix administered?
Hemgenix is supplied as a suspension for intravenous infusion. Its recommended dose is 2 x 1013 genome copies (gc) per kilogram (kg) of body weight.
The therapy is available at a concentration of 1 x 1013 gc/mL, and is provided in kits containing 10 to 48 single-use bottles. Each kit makes up a dosage unit based on the patient’s body weight.
Before administration, the therapy should be diluted in a normal saline solution (0.9% sodium chloride solution) and infused at a rate of 500 mL per hour (8 mL/min). Following preparation, Hemgenix should be administered within a period of 24 hours.
The medication should be stored at room temperature and protected from light.
Hemgenix in clinical trials
Phase 2b trial
An ongoing Phase 2b trial (NCT03489291), launched in 2018, is assessing the safety and effectiveness of a single dose of Hemgenix (as AMT-061) in three men with severe hemophilia B living in the U.S.
Two-year data showed the therapy was generally safe, and led to stable and sustained FIX activity in all three participants. Their levels reaching up to more than 50% of what would be considered normal in one participant.
Hemgenix’s use also prevented the occurrence of spontaneous bleeds and the need for FIX replacement therapy in two of the three patients, as well as the need for prophylaxis in all these men. Participants are continuing to be monitored for five years, with the trial expected to conclude in September 2023.
The approval of Hemgenix in the U.S. was mainly supported by data from an open-label Phase 3 study called HOPE-B (NCT03569891). This trial is evaluating Hemgenix’s five-year safety and effectiveness in 54 men with moderate to severe hemophilia B in the U.S. and in Europe. HOPE-B is the largest trial to date of an experimental gene therapy for hemophilia B.
Top-line, six-month results showed the gene therapy significantly increased FIX activity, reaching a mean of 37.2% of normal levels and meeting the trial’s main goal. The therapy also was found to strongly reduce bleeds and the need for preventive treatment.
One-year data from HOPE-B demonstrated Hemgenix had sustained and durable effects, with patients achieving a mean of 41.5% of normal FIX activity levels and their annualized rate of bleeds requiring treatment dropping by 80% or more. All but two patients (96.3%) were able to discontinue routine preventive treatment and remain prophylaxis-free. The use of FIX replacement therapies also fell by 96%.
Data at 1.5 years post-treatment also showed the therapy significantly increased FIX activity, reaching a mean of 36.9% of normal. FIX activity levels remained high — at a mean of 36.7% of normal — two years after infusion.
Seven to 18 months after the infusion, the annualized bleeding rate had dropped by 54% — from more than four bleeds per year to less than two, on average — from the trial’s lead-in period.
Nearly all patients (94%) treated with Hemgenix stopped taking their routine FIX infusions and no longer required prophylaxis.
These benefits were seen regardless of preexisting antibodies against the therapy’s viral carrier, AAV5, which can limit the therapy’s efficacy, suggesting nearly all hemophilia B patients may benefit from treatment.
The gene therapy also was found to be generally safe, with no treatment-related serious adverse events and no reported development of antibodies against the delivered FIX. Among the most common side effects reported were liver enzyme elevations, headache, flu-like symptoms, infusion-related reactions, fatigue, and feeling unwell.
Both trials had been placed on hold by the FDA in December 2020 after a HOPE-B participant developed hepatocellular carcinoma, a type of liver cancer. Following an independent investigation that showed it was very unlikely that the therapy contributed to this cancer’s development, the FDA lifted the clinical hold in April 2021.
HOPE-B is expected to conclude in March 2025.
Common side effects of Hemgenix
The most common side effects associated with Hemgenix are:
- elevated liver enzymes.
- high levels of creatine kinase in the blood.
- flu-like symptoms.
- infusion-related reactions.
Infusion reactions, including severe allergic reactions, may occur during treatment with Hemgenix. Symptoms may include chest tightness, headaches, abdominal pain, flu-like symptoms, and shivering. Patients should be monitored during infusion and for at least three hours after the end of treatment. If infusion reactions occur, the infusion should be slowed or stopped. Treatment can resume if symptoms are resolved.
Increases in the levels of liver enzymes, such as transaminases, may occur with treatment. As such, their levels should be monitored continuously once weekly for three months after treatment administration to minimize the risk of liver toxicity. In all patients whose liver enzyme levels are higher than normal, monitoring should continue until levels normalize. Corticosteroid treatment also may be considered if such elevations occur.
Because Hemgenix uses a viral vector to deliver genetic material to patient cells, it may in theory increase the risk of liver cancer. Patients who have a history of liver disease or those with chronic alcohol consumption should undergo regular liver imaging exams and be tested for a liver protein called alpha-fetoprotein in the five years following treatment.
Development of antibodies
Development of antibodies, or inhibitors, against FIX may occur during treatment with Hemgenix. In some cases, this may lower the treatment’s efficacy. The therapy’s label recommends regularly monitoring FIX activity and inhibitor levels.
Use in pregnancy and breastfeeding
According to animal studies, Hemgenix did not cause harm to developing fetuses. However, the therapy is not intended for use in female patients.
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