Last updated July 21, 2022, by Teresa Carvalho, MS
✅ Fact-checked by Joana Carvalho, PhD
What is Advate for hemophilia?
How does Advate work?
Advate contains a substance called octocog alfa — a recombinant, or lab-made form of clotting factor VIII (FVIII). This is the clotting protein that is missing or defective in people with hemophilia A.
The clotting factor that makes up Advate is able to replace naturally produced FVIII, allowing for the control and prevention of bleeds in hemophilia A patients.
Who can take Advate?
The therapy was originally approved by the U.S. Food and Drug Administration (FDA) in 2003 to treat children and adults with hemophilia A. It is used for the control and prevention of bleeds, and to prevent excessive bleeding during surgery.
In 2011, Advate was approved in the U.S. as a routine prophylactic treatment to prevent and lower the frequency of bleeding episodes.
The treatment is approved in more than 50 nations, including Australia and Canada, as well as in countries in Europe, South America, and Asia.
Who should not take Advate?
Advate should not be used by patients who have allergic reactions, including severe and potentially life-threatening reactions to:
- mouse or hamster proteins
- other constituents of the product, such as mannitol, trehalose, sodium chloride, histidine, Tris, calcium chloride, polysorbate 80, and/or glutathione
The therapy is not indicated for the treatment of von Willebrand disease, another inherited bleeding disorder.
How is Advate administered?
Advate is available as a white to off-white powder supplied in single-use bottles containing 250, 500, 1,000, 1,500, 2,000, 3,000, and 4,000 international units (IU).
The treatment is injected directly into a vein. Injection frequency depends on the type of bleed and the physician’s recommendation. For prophylactic, or preventive, treatment, patients should be given:
- a dose from 20 to 40 IU per kilogram of body weight (IU/kg), every other day (three to four times a week)
- a dose aimed at maintaining FVIII levels at 1% or higher, which may be given once every three days
For the control and prevention of bleeds, patients should receive:
- a dose from 10 to 20 IU/kg, given every 12–24 hours (8–24 hours for patients under age 6), in the case of minor bleeds
- a dose from 15 to 30 IU/kg, given every 12–24 hours (8–24 hours for patients under age 6), in the case of moderate bleeds
- a dose from 30 to 50 IU/kg, given every 8–24 hours (6–12 hours for patients under age 6), in the case of major bleeds
For minor surgical procedures, a single dose of 30 to 50 IU/kg of Advate should be given one hour before surgery, and then repeated every 12–24 hours if needed to control bleeding. For major surgical procedures, a single dose of 40 to 60 IU/kg of Advate should be given before surgery, and then every 8–24 hours (6–24 hours for patients under age 6) to maintain FVIII levels in the desired range until healing is complete.
Advate should be stored in the refrigerator, but patients should wait for the medication to reach room temperature before injection. It can be kept at room temperature, for up to six months, but in such cases, it should not be put back in the refrigerator.
The medication should be reconstituted, or diluted, with 2 or 5 mL of sterile water before injection. After reconstitution, Advate should be administered within three hours.
Patients should not self-inject Advate unless they have been trained by an experienced healthcare provider.
Advate in clinical trials
Phase 2/3 trials
Advate’s original approval was based on the results of Phase 2/3 clinical trials evaluating its safety and efficacy on bleed treatment and prevention in previously treated hemophilia patients.
A main study involving 111 patients compared Advate with another approved therapy, called Recombinate, to assess if the two medicines were equivalent.
The study evaluated the number of bleeding episodes and rated Advate’s effectiveness in stopping bleeds on a scale from none to excellent. Advate’s effectiveness was considered excellent or good in 86% of 510 new bleeding events. Additionally, 81% of these episodes required only a single treatment with Advate.
Phase 4 trial
The approval of Advate as a routine prophylactic treatment came after the results of a Phase 4 study comparing two preventive regimens to an on-demand treatment plan. A total of 53 patients with severe or moderately severe hemophilia A were included in this study.
Results showed that Advate significantly reduced the median annual bleeding rate — from 44 bleeds per patient per year to one bleed per patient per year — when compared with an on-demand regimen. The study also found that 42% of patients had zero bleeding episodes over one year on prophylaxis treatment with Advate.
Data from 12 clinical trials (Phase 1 through 4) were analyzed to assess the safety and tolerability of Advate in treating severe hemophilia A in children and adults. The study covered data over more than 10 years and included 418 patients.
Most adverse events associated with Advate were not serious, the results showed. Among those considered serious, the most common were related to the development of inhibitors (neutralizing antibodies) against FVIII, device-related infection, and fever. No deaths or cases of hypersensitivity reactions were observed.
The trial’s primary goal is to describe joint health in individuals receiving Advate in a routine clinical practice settings using any treatment dosage. Secondary goals include evaluating long-term results, annualized (joint) bleeding rates, and safety.
According to an interim analysis of this study, which included seven-year data from 711 patients, prophylactic Advate was superior to on-demand treatment at lowering the number of spontaneous and joint bleeds.
This study is expected to be completed in January 2025.
Common side effects of Advate
The most common adverse events (side effects) associated with Advate include:
- upper respiratory tract infection
- common cold symptoms
- runny nose
- joint pain
- limb injury
Patients may develop a severe allergic reaction to treatment. Advate is contraindicated, or not recommended, for people with known allergies to mouse or hamster proteins or to other therapy components. If symptoms occur, Advate should be discontinued and patients should get emergency treatment immediately.
Development of inhibitors
Patients also may develop neutralizing antibodies against FVIII, making Advate less effective. This issue occurs mainly in those who have not been previously treated or received a correct dose. Monitoring should be done to check for the possible development of inhibitors. Those taking Advate should talk with their healthcare team right away if bleeding does not stop after treatment.
Use in pregnancy and breastfeeding
It is currently unknown if Advate can affect a developing fetus during pregnancy or be passed to a nursing infant via breast milk. Patients who are pregnant, plan to become pregnant, or breastfeed should talk with their healthcare team.
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