Roctavian

What is Roctavian?

Roctavian is a gene therapy that can be given as a one-time infusion to adults with severe hemophilia A. This treatment may be done after a blood test has shown they don't have antibodies against a specific adenovirus, AAV5.

Roctavian uses a modified viral vector to deliver a copy of the factor 8 gene to the liver cells. This allows the body to make clotting factors on its own. Clotting factors help the blood clot, and reduce or prevent bleeding. The modified virus is free of viral DNA, and it does not infect humans.

Warning

You should not take Roctavian if:

• If you have an infection active or a long-term illness that your medicines are not controlling
• Have scarring on the liver (significant cirrhosis or liver fibrosis).
• Roctavian (an inactive component) contains mannitol.

Can cause hypersensitivity reactions or anaphylaxis. You must be monitored for a minimum of 3 hours following Roctavian. Your doctor may slow down or stop the infusion if you experience symptoms. They will also give you appropriate treatment. Once symptoms have resolved, they can restart at a lower rate. If anaphylaxis is experienced, the infusion will stop. If ALT levels are elevated, your doctor will prescribe corticosteroids if necessary. Continue to monitor ALT levels until they return to baseline. The factor VIII activity level and other laboratory values are also monitored, since ALT elevation can be accompanied with a decrease in the activity of factor VIII. Thromboembolic reactions can occur when factor VIII activity is elevated above the upper limit normal (ULN), as has been observed following Roctavian injection. Those with cardiovascular risk factors and thrombosis risk factors are at greater risk. It is important to have an annual liver ultrasound for people who are at risk of liver cancer (such as those with hepatitis C or B, non-alcoholic liver disease, chronic drinking, non-alcoholic liver steatohepatitis and advanced age). Alpha-fetoprotein will be tested following administration.

Similar/related drugs

Tranexamic Acid , Desmopressin , DDAVP , Cyklokapron , antihemophilic factor , Hemlibra

Before you take this drug

If you have an allergy to mannitol, or any other ingredient in the infusion, then you should not take Roctavian.

Ensure you have all of your vaccines up-to-date before taking Roctavian.

Tell your doctor if:

• Any general risk factors such as high blood pressure, cholesterol or blood sugar, use of oral contraceptives, a history of DVT, or being overweight.
• HIV infection
• Immunity is lowered
• A history of factor VIII inhibitors
• A female partner who plans to get pregnant within six months of the treatment. The vector DNA can be detected for up to 182 days after treatment.

Roctavian should not be administered to women.

No data are available on the use Roctavian by pregnant women or nursing mothers.

How to take Roctavian?

Roctavian can be administered by a healthcare provider as a one-time, single infusion into a vein at a medical facility.

• The recommended dose is 6 x10 ¹³ vector genes per kilogram of weight. A 70kg person would receive 210ml Roctavian, which is equivalent to 27 vials. Each vial contains 16 x10 ¹³ vg per 8ml. Round to the nearest 8ml vial.
• The infusion can take up to 5 hours, depending on how well you react to the infusion and your weight.
• You will be closely monitored during and after your infusion for possible side effects. You will be told by your healthcare provider when you are allowed to go home.
• The Roctavian treatment or any other gene therapy is not repeatable.

You will be asked to join a 15-year database after treatment with Roctavian to study its long-term effectiveness and safety. While Roctavian is beneficial to most patients, some may not benefit. Your doctor will monitor the results of your lab tests, and discuss with you whether or not you should continue prophylaxis. They may also ask you if you have any injuries, surgeries, or bleeding.

What should be avoided?

For the first year, avoid drinking alcohol. Speak to your doctor regarding how much alcohol you can tolerate after the first 12 months. You should both use reliable contraception for the next 6 months. Don't donate semen at least six months after treatment. Don't donate blood, organs or tissues. Avoid live vaccines

Side effects of Roctavian

If you experience symptoms of an allergic reaction such as hives, difficulty breathing, swelling of the face, lips, throat, or tongue, your doctor will send emergency medical assistance.

Serious side effects include:

• Hepatotoxicity
• Serious Infusion-Related Reactions
• Thromboembolic Events

ROCTAVIAN is most commonly associated with the following side effects:

• Abdominal pain
• Fatigue
• Headache
• Reactions to Infusion
• Nausea

Some of the changes in laboratory results are also consistent with Roctavian's actions within your body.

There are other side effects that ROCTAVIAN can cause. Speak to your doctor about possible side effects. Report side effects by calling BioMarin Pharmaceutical Inc. 1-866-906-6100, or FDA 1-800-FDA-1088.

Interaction with other drug

Roctavian has not been subjected to any interaction studies. Review all medications before administration to determine if any changes should be made to avoid anticipated interactions. This includes their impact on liver function or clotting risks. The following medications should not be taken with Roctavian.

• Efavirenz
• Isotretinoin
• Live vaccines.

Agents which increase or decrease the plasma concentration of a corticosteroid (such as those that increase cytochrome P4503A4) can reduce the effectiveness of the corticosteroid regime used with Roctavian, or increase its side effects. It is important to monitor liver function and factor VIII levels closely when a new medication has been started (e.g., every two weeks to weekly for the first one month). This will allow you to evaluate any potential side effects. This list does not include all possible interactions. Tell your doctor if you are using any new or existing medications, or if you plan to start or stop taking them. This includes prescription and non-prescription medicines, vitamins, herbal supplement, and vaccines.