Hemgenix (etranacogene dezaparvovec-drlb) is a one-time gene therapy used to treat certain people with hemophilia B. Hemophilia B is an inherited bleeding disorder caused by low levels of factor IX.
Factor IX is a protein the body needs to form blood clots. In people with hemophilia B, a change in the F9 gene keeps the body from making enough working factor IX.
Hemgenix uses a modified virus to carry a working copy of the factor IX gene into liver cells. These cells can then make factor IX, which may reduce bleeding and the need for regular factor IX treatments.
Like all medicines, Hemgenix can cause side effects. Some happen during or shortly after the infusion, while others are found through blood tests and require follow-up monitoring. Keep reading to learn about Hemgenix side effects, follow-up monitoring, and what to expect before and after treatment.
What Are the Most Common Side Effects of Hemgenix?
Here are the most common side effects reported in clinical studies of Hemgenix:
- Increased levels of liver enzymes
- Increased levels of creatine kinase
- Infusion-related reactions
- Headache
- Flu-like symptoms
- Tiredness (fatigue)
- Feeling generally unwell
- Nausea
Other side effects are possible. Tell your health care provider about symptoms that concern you, worsen, or do not improve.
The sections below provide more details about some common and potentially serious side effects of Hemgenix.
Infusion-Related Reactions or Allergic Reactions
Hemgenix is given as a one-time infusion into a vein. In studies, infusion-related reactions happened in about one-third of people treated with Hemgenix. Symptoms may begin during or after the infusion. They include:
- Chest tightness
- Headache
- Stomach pain
- Lightheadedness
- Chills or shivering
- Flushing or rash
- High blood pressure
Serious allergic reactions are also possible. A health care provider will monitor you throughout the infusion (which usually takes about one to two hours) and for at least three hours afterward.
If a reaction happens, the infusion may be slowed or stopped. Once symptoms go away, it may be restarted more slowly. Medicines, such as corticosteroids or antihistamines, may be given to treat the reaction.
Tell your health care provider right away if you start having signs of a serious allergic reaction, such as trouble breathing, throat tightness, or swelling of the face, mouth, or neck.
Increased Liver Enzymes
Hemgenix works inside liver cells and can cause liver enzyme levels to rise. This may happen if the immune system reacts to the treated liver cells. Higher levels of liver enzymes can reduce how well Hemgenix works.
Mostly, increases in liver enzyme levels do not cause symptoms and are found through blood tests. Your health care provider will usually check your liver enzymes:
- Weekly for the first three months
- Monthly after that for up to one year
- Longer if your levels remain high
If liver enzyme levels rise, your health care provider may prescribe a corticosteroid and continue checking your liver enzymes and factor IX activity.
Contact your health care provider if you notice possible signs of a liver problem, such as yellow skin or eyes, dark urine, unusual fatigue, stomach pain, or loss of appetite.
Frequently Asked Questions About Hemgenix
Hemgenix requires testing before treatment and close follow-up afterward. The answers below explain what to expect and why ongoing monitoring is important.
What should I know about factor IX inhibitors?
Some people make antibodies called factor IX inhibitors, which block factor IX. You will be tested for these antibodies before receiving Hemgenix. Hemgenix should not be used if you currently have factor IX inhibitors or have had them in the past.
Your health care provider may test for inhibitors again after treatment if:
- Bleeding is not controlled
- Bleeding returns
- Your factor IX activity falls
Hemgenix does not work equally well for everyone. Some people may not make enough factor IX after treatment or may later need factor IX replacement again. Regular blood tests and tracking bleeding episodes will help your health care provider see how well treatment is working.
Will I need regular tests after Hemgenix?
Yes. Regular blood testing is important after Hemgenix treatment. Your health care provider will order various tests, including tests for liver enzyme levels, factor IX activity, and factor IX inhibitors when needed.
For several weeks after receiving Hemgenix, you may still need factor IX replacement. Factor IX given by infusion can affect blood test results, so your health care provider will consider the timing of these treatments when reviewing your factor IX levels.
Hemgenix also carries a theoretical risk of liver cancer because small amounts of the gene therapy’s DNA may become part of liver-cell DNA. Hemgenix has not been shown to cause liver cancer in clinical studies.
People with certain risk factors for liver cancer may need liver ultrasounds and certain blood tests each year for five years after treatment. Risk factors for liver cancer include cirrhosis, advanced liver scarring, hepatitis B or C, fatty liver disease, long-term heavy alcohol use, and older age.
When can I return to normal activities after Hemgenix?
Ask your health care provider when it is safe to return to work, exercise, sports, travel, or activities that may increase your risk of bleeding.
Hemgenix does not work right away. In the main clinical study, factor IX made by the body was first detected during the third week after treatment. This means it may take several weeks for bleeding control to improve. During this time, you may still need factor IX replacement and should take precautions to lower your risk of bleeding.
Your health care provider can give guidance based on your factor IX levels, bleeding history, and the activity you plan to do.
Can Hemgenix be given more than once?
No. Hemgenix can only be given once.
After treatment, the immune system makes antibodies against the virus (adeno-associated virus type 5, or AAV5) that carries the gene into the liver. Having antibodies against AAV5 may affect treatment response in some people. In the main clinical study, one participant with a high AAV5 antibody level did not respond and continued routine factor IX treatment.
If Hemgenix does not offer enough bleeding protection, you may need to continue or restart factor IX treatment to prevent bleeding.
Is Hemgenix a permanent cure?
Hemgenix is designed to provide long-term factor IX production after one infusion, but it should not be considered a guaranteed permanent cure.
It does not remove the original gene change that causes hemophilia B; results vary between people, and researchers do not yet know exactly how long the benefits will last. Continued follow-up remains important even if bleeding improves and routine factor IX treatment is no longer needed.
How can I reduce my risk of problems?
Complete all testing and follow-up recommended by your health care provider. Share your health history, medicines, and supplements, and report any new or worsening symptoms. Follow your current bleeding treatment plan until your hemophilia care team tells you to make a change.
Your hemophilia treatment team can help you weigh the possible benefits and risks of Hemgenix and understand what to expect before and after the infusion.