ROCTAVIAN™ Gene Therapy for Hemophilia A

ROCTAVIAN™ (valoctocogene roxaparvovec-rvox) is a one-time gene therapy treatment for severe hemophilia A, caused by deficiency of the factor VIII clotting protein. It delivers a healthy copy of the F8 gene with instructions for making factor VIII to cells in the liver, enabling the body to make factor VIII on its own.

ROCTAVIAN can prevent or reduce bleeding episodes, but it does have some potential risks, described below. Also, if you receive ROCTAVIAN you will not be able to receive another similar gene therapy for hemophilia.

The U.S. Food and Drug Administration has approved ROCTAVIAN for men age 18 and older with severe hemophilia A without factor VIII inhibitors. People who receive ROCTAVIAN should have no known liver disease or infections and should test negative for antibodies to adeno-associated virus, which is used to deliver the F8 gene.

ROCTAVIAN provides genetic instructions telling the body to make the factor VIII clotting protein. The F8 gene is delivered into your cells by a virus called AAV (adeno-associated virus). AAV, sometimes referred to as a “vector,” does not cause infection and has been modified to carry the F8 gene. 

Once in the body, ROCTAVIAN goes mostly to liver cells where factor VIII can be made. If the liver cells successfully begin to make factor VIII and secrete it into the blood, the risk of bleeding is reduced.

ROCTAVIAN is given as a one-time intravenous (IV) infusion in our outpatient infusion area. The infusion requires one or two hours. You will be monitored during the infusion and for at least three hours afterward, but you will not need to be admitted to the hospital.

After treatment, we will follow you closely with weekly blood tests for at least 26 weeks to ensure your liver remains healthy and that you are making factor VIII. If your liver enzymes are abnormal you may need to start on a medication such as prednisone to dampen your body’s immune response to ROCTAVIAN. If your liver remains healthy, or once you stop this medication, you will only need blood work every two weeks until you hit the one-year mark. In year 2, will need blood work only every three months, and then every six months in year 3 and beyond.

You will also need a liver ultrasound and an alpha-fetoprotein blood test once a year for at least five years.

To prevent harm to your liver, you should avoid alcohol for at least one year after the infusion and limit alcohol after that. We also suggest avoiding herbal products and nutritional supplements that may affect your liver. Because ROCTAVIAN’s safety for unborn children is unknown, you should avoid semen donation or pregnancy for a period of six months after you receive ROCTAVIAN.

At this writing, what we know is based on data from 112 people receiving ROCTAVIAN and followed for at least six months before and three years after their infusion. ROCTAVIAN worked for 80 percent of recipients; others did not respond or eventually stopped responding to treatment. At follow-up an average 2.3 years after ROCTAVIAN treatment, 12 percent of recipients went back on prophylaxis to prevent bleeding. The number of annual bleeding episodes was reduced, on average, by more than half, from 5.4 to 2.6 episodes per year.

• Reactions to the infusion including allergic reactions sometimes happen. Symptoms may include hives, itching, a rash, sneezing, coughing, shortness of breath, a runny nose, watery eyes, tingling throat, nausea, diarrhea, lowered blood pressure, a fever, and chills. We will treat these and slow or pause the infusion as needed. If you have a severe allergic reaction (anaphylaxis) the infusion will stop.
• Liver toxicity (hepatotoxicity) usually doesn’t cause symptoms, but may be found on blood tests in the weeks and months after ROCTAVIAN administration. You may need to start oral corticosteroid treatment (prednisone) or another medication that dampens your immune system response.
• Blood clots: Sometimes ROCTAVIAN can increase factor VIII activity above the normal range, posing an increased risk for blood clots (thromboembolism). We will check factor VIII activity in your follow-up blood work.
• Cancer is a theoretical risk because ROCTAVIAN can also insert into the DNA of other human body cells. Although no cancers caused by ROCTAVIAN have been reported at this writing, we monitor for signs of liver cancer (hepatocellular carcinoma) if you have risk factors such as hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, or advanced age.

Because this therapy is so new, it’s not clear how many health insurance providers cover this therapy. We encourage you to talk with your insurance company and care team. Boston Children’s Financial Services staff will guide you through the insurance approval process.