Adynovate/Adynovi for Hemophilia

Last updated July 22, 2022, by Teresa Carvalho, MS

Fact-checked by Joana Carvalho, PhD


What is Adynovate/Adynovi for Hemophilia?

Adynovate or Adynovi (rurioctocog alfa pegol) is an injectable factor replacement therapy for the treatment and prevention of bleeding episodes in patients with hemophilia A.

The treatment was initially developed by Baxter, now part of Takeda Pharmaceuticals.

How does Adynovate/Adynovi work?

Adynovate/Adynovi is based off Advate, an artificially produced version of coagulation factor VIII (FVIII) — a protein required for blood clotting that is missing or is defective in hemophilia A patients.

The difference between the two therapies is that Adynovate/Adynovi contains polyethylene glycol (PEG), a nontoxic and nonimmunogenic molecule that allows it to remain in the blood for a longer period of time.

By mimicking FVIII, Adynovate/Adynovi allows blood clots to form, effectively stopping or preventing bleeds. Like Advate, Adynovate/Adynovi may also be used to prevent excessive bleeding during surgery.

Who can take Adynovate/Adynovi?

Adynovate was first approved by the U.S. Food and Drug Administration (FDA) in 2015 as an on-demand treatment to control bleeding episodes and as a routine prophylactic, or preventive, treatment to reduce the number of bleeds in adults and children ages 12 and older with hemophilia A. In 2018, it was approved in Europe for the same indication and sold under the brand name Adynovi.

In 2016, the FDA extended Adynovate’s approval to children under age 12 and also approved it to control bleeds occurring during surgery in both adults and children.

Who should not take Adynovate/Adynovi?

Adynovate/Adynovi should not be used by patients who have had previous severe and potentially life-threatening allergic reactions to:

  • Advate
  • mouse or hamster proteins
  • other components of the treatment

The therapy is not indicated for the treatment of von Willebrand disease, another inherited bleeding disorder.

How is Adynovate/Adynovi administered?

Adynovate/Adynovi is available as a white to off-white powder supplied in single-use bottles containing 250, 500, 750, 1,000, 1,500, 2,000, and 3,000 international units (IU).

Dosing is based on a patient’s body weight, so it may change if patients gain or lose weight. The treatment is injected directly into a vein. Injection frequency depends on the type of bleed and the patient’s clinical condition.

For prophylactic treatment, the medication should be given at the following doses:

  • 40 to 50 IU per kilogram of body weight (IU/kg), twice weekly, in the case of adults and adolescents ages 12 and older
  • 55 IU/kg, twice weekly, in the case of children under age 12, up to a maximum of 70 IU/kg

For the control and prevention of bleeds, patients should receive the following doses:

  • 10 to 20 IU/kg, given every 12–24 hours until the bleed is resolved, in the case of minor bleeds
  • 15 to 30 IU/kg, given every 12–24 hours until the bleed is resolved, in the case of moderate bleeds
  • 30 to 50 IU/kg, given every 8–24 hours until the bleed is resolved, in the case of major bleeds

For minor surgical procedures, a single dose of 30 to 50 IU/kg should be given one hour before surgery and then repeated after 24 hours if needed to control bleeding. For major surgical procedures, a single dose of 40 to 60 IU/kg should be given before surgery, and then every eight to 24 hours ( six to 24 hours for patients under age 12) to maintain FVIII levels in the desired range until healing is complete.

Adynovate/Adynovi should be injected directly into a vein over five minutes or less, at a maximum infusion rate of 10 mL per minute.

Adynovate/Adynovi powder should be stored in the fridge, but the medication should reach room temperature before administering it. It can be kept at room temperature for up to three months, but should not be put back in the fridge. The medication should be stored in its original package to be protected from light.

The medication should be reconstituted, or diluted, with 2 or 5 mL of sterile water before injection. After reconstitution, Adynovate/Adynovi should be administered right away or within three hours, but should not be put on the fridge.

Patients should not self-inject Adynovate/Adynovi unless they have been trained by an experienced healthcare provider.

Adynovate/Adynovi in clinical trials

Phase 1 and Phase 2/3 trials

The safety and pharmacological properties of Adynovate/Adynovi were first assessed in a Phase 1 trial (NCT01599819) in 19 patients. This was followed by a pivotal Phase 2/3 trial (NCT01736475) enrolling 159 previously treated patients that evaluated the safety, effectiveness, and pharmacological properties of Adynovate/Adynovi when given as a prophylactic or on-demand therapy.

Results of the trials showed the mean half-life of Adynovate/Adynovi was 1.4- to 1.5-times longer than that of Advate. Of note, half-life is the period of time it takes for a compound’s dose to drop to half of that originally administered.

The median annual bleed rate (ABR) on prophylaxis was 1.9, while patients treated on-demand had a median ABR of 41.5. The study also found that about 40% of the patients on prophylaxis were bleed-free. Results also showed that about 96% of bleeding episodes were successfully treated with one or two infusions.

Phase 3 trials

A Phase 3 trial (NCT02210091) evaluated the safety, effectiveness, and pharmacological properties of Adynovate/Adynovi in previously treated children younger than age 12. Results of the study showed that 38% of the patients had zero bleeds, and up to 91% of all bleeds were successfully treated with one or two injections. No inhibitors were detected during the study, which found a significant reduction in pain, as well as an increase in the children’s physical activity.

Another Phase 3 study (NCT01913405) evaluated the effectiveness and safety of Adynovate/Adynovi in 21 previously treated patients undergoing surgery. Results of the trial demonstrated “excellent” overall effectiveness before and during surgery in all 24 procedures with available assessments.

Common side effects of Adynovate/Adynovi

The most common adverse events associated with Adynovate/Adynovi are:

  • headache
  • diarrhea
  • rash
  • nausea
  • dizziness
  • urticaria

Allergic reactions

Patients may develop a severe allergic reaction to the treatment. Patients who have had severe allergic reactions to Adynovate/Adynovi, Advate, mouse or hamster proteins, or any component of the treatment should not use it. If symptoms occur, the medication should be stopped, and patients should get emergency treatment immediately.

Development of inhibitors

Development of FVIII neutralizing antibodies (inhibitors) may occur, which may render Adynovate/Adynovi less effective. Patients should be monitored for FVIII levels and the development of inhibitors. A patient’s healthcare team should be informed right away if bleeding does not stop after the treatment.

Use in pregnancy and breastfeeding

It is still unknown if Adynovate/Adynovi can affect the developing fetus or pass to breast milk. Patients who are pregnant, plan to become pregnant, or breastfeed should inform their healthcare team.

 


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