Obizur® (antihemophilic factor [recombinant], porcine sequence) is a recombinant analog of porcine factor VIII (FVIII) produced in BHK (baby hamster kidney) cells. It is a lyophilized powder for solution to use as an intravenous injection. Obizur is indicated for the on-demand treatment and control of bleeding episodes in adult patients with acquired hemophilia A (AHA). It was initially approved by the US Food and Drug Administration (FDA) on October 24, 2014. Obizur is manufactured by Baxalta Incorporated, a Takeda company.1,2 

Acquired Hemophilia A and Its Impact

Acquired hemophilia A is a bleeding disease with fatal potential that primarily affects geriatric individuals. It is a disease in which the body develops autoantibodies, which are specialized inhibitor proteins that attack coagulation FVIII, an important blood-clotting protein. Because the malfunction of this protein inhibits blood clotting, people with this condition frequently experience abnormal bleeding into the skin, muscles, or other soft tissues, as well as postoperative bleeding. Pregnancy, immune system diseases, cancer, and allergic reactions to specific medicines are among the known causes of AHA. However, the reasons for 50% of cases remain unknown.3

Mechanism of Action

In patients with AHA, Obizur temporarily restores the suppressed endogenous FVIII required for successful hemostasis. Patients with AHA have normal FVIII genes but produce autoantibodies against their own FVIII (ie, inhibitors). These autoantibodies neutralize circulating human FVIII, resulting in a procoagulant protein deficit. The activated partial thromboplastin time (aPTT) assay, a standard in vitro test for FVIII biological activity, shows that AHA causes a longer clotting time. During treatment with Obizur, the aPTT should normalize, but aPTT normalization must not be utilized as a marker of efficacy.4

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Efficacy in Trials and Trial Results

Obizur was approved by the FDA after a global, prospective, controlled, multicenter phase 2/3 open-label clinical trial evaluated its efficacy in treating serious bleeding events in adults with AHA (29 cases evaluated for safety and 28 for efficacy). At 24 hours following the initial infusion, all participants treated with Obizur demonstrated a positive reaction, which was defined as an effective or partially effective response with bleeding stopped or decreased and clinical improvement. The initial bleeding episode was successfully treated in 86% of cases. The ability to discontinue or modify the dose and/or dosing frequency of Obizur was used by the investigators to measure overall treatment effectiveness.5

Warnings, Precautions, and Adverse Reactions

Hypersensitivity reactions, including anaphylaxis, are possible. There are traces of hamster proteins in the product. Angioedema, chest tightness, hypotension, lethargy, nausea, vomiting, paresthesia, restlessness, wheezing, and dyspnea are initial signs of allergic reactions that might escalate to anaphylaxis. Obizur should be immediately stopped in such cases.6

Antibodies to Obizur have been found, as well as anamnestic reactions associated with an increase in human and/or porcine FVIII inhibitors. Patients should be monitored for the formation of antibodies to Obizur using suitable assays. If the plasma FVIII level does not rise as expected after Obizur treatment, the presence of an antiporcine FVIII antibody should be suspected. Obizur should be terminated and the patient should be started on other treatments, such as an FVIII bypassing drug, in cases with suspected inhibitory antibodies and an absent clinical response.7 In clinical trial data, the most common adverse reaction observed was the development of inhibitors to porcine FVIII, which was noted in more than 5% of cases.1

References

  1. Obizur. Prescribing information. Baxalta US Inc.; 2021. Accessed January 3, 2022.
  2. FDA approves Baxter’s Obizur [antihemophilic factor (recombinant), porcine sequence], for acquired hemophilia A. News release. Baxter; October 24, 2014.
  3. Obizur antihemophilic factor (recombinant) for the treatment of acquired haemophilia A. Clinical Trials Arena. Accessed January 3, 2022.
  4. Obizur (antihemophilic factor- recombinant, porcine sequence kit. DailyMed. Updated October 26, 2021. Accessed January 3, 2022.
  5. Obizur [antihemophilic factor (recombinant), porcine sequence]. CenterWatch. Accessed January 3, 2022.
  6. Product monograph including patient medication information: Obizur. Takeda Canada Inc. Updated September 22, 2021. Accessed January 3, 2022.
  7. Obizur [antihemophilic factor (recombinant), porcine sequence]. Takeda. Accessed January 3, 2022.

Reviewed by Hasan Avcu, MD, on 1/3/2022.

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