Adynovate (rurioctocog alfa pegol) is an injectable factor replacement therapy marketed by Takeda Pharmaceuticals for the treatment and prevention of bleeding episodes in patients ages 12 and older with hemophilia A.
The treatment was first approved by the U.S. Food and Drug Administration (FDA) in 2015 as Adynovate. In 2018, it was approved in Europe under the name Adynovi.
How does Adynovate work?
Adynovate is based on Advate, an artificially produced version of coagulation factor VIII (FVIII) — a protein required for blood clotting that is defective in hemophilia A patients.
The difference between the two therapies is that Adynovate contains polyethylene glycol (PEG), a non-toxic and non-immunogenic molecule that allows it to remain in the blood for a longer period of time.
By mimicking FVIII, Adynovate allows blood clots to form, effectively stopping or preventing bleeds. Like Advate, Adynovate also may be used to prevent excessive bleeding during surgery.
Adynovate in clinical trials
The safety and pharmacological properties of Adynovate were first assessed in a Phase 1 trial (NCT01599819) in 19 patients. This was followed by a pivotal Phase 2/3 trial (NCT01736475) in 159 previously-treated patients that evaluated the safety, effectiveness, and pharmacological properties of Adynovate when given as a prophylactic (preventive) or on-demand therapy.
Results of the trials showed the mean half-life of Adynovate 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 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.
A Phase 3 trial (NCT02210091) evaluated the safety, effectiveness, and pharmacological properties of Adynovate 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 in previously-treated patients undergoing surgery. Results of the trial from 15 patients demonstrated “excellent” overall effectiveness before and during surgery in all cases, with no related adverse events. Following surgery, all treatments were rated as “excellent” except for one minor (dental) procedure, which was rated as “good.”
An ongoing Phase 3 trial (NCT02615691), scheduled to run through 2023, is investigating Adynovate’s safety, immunogenicity — ability to trigger an immune response — and hemostatic effectiveness, or its ability to stop bleeds. This study involved previously untreated and minimally treated children younger than 6 with severe hemophilia A.
Adynovate is available in single-use bottles containing approximately 250, 500, 750, 1,000, 1,500, 2,000, or 3,000 international units (IU). Dosage is based on a patient’s body weight, so it may change if patients gain or lose weight.
For minor bleeds, a 10 to 20 IU/Kg dose should be given and repeated every 12 to 24 hours until the bleed is resolved. In moderate bleeding cases, patients should take a 15 to 30 IU/Kg-dose that has to be repeated every 12 to 24 hours until the bleeds are solved. For major bleeding, patients should take a dose of 30 to 50 IU/Kg and repeat every eight to 24 hours until bleeding stops.
The most common adverse events associated with Adynovate are headache, diarrhea, rash, nausea, dizziness, and urticaria, which is a skin rash of round, red welts.
Patients who have previously had severe allergic reactions to Adynovate, Advate, mouse or hamster proteins, or any component of the treatment should not use it.
Development of FVIII neutralizing antibodies (inhibitors) may occur, which may render Adynovate less effective.
Last updated: Jan. 28, 2022, by Teresa Carvalho MS
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