Treatment to help control bleeding in acquired hemophilia A (AHA)
Treatment to help control bleeding in acquired hemophilia A (AHA)
Study Design
The efficacy and safety of OBIZUR for the treatment of serious bleeding episodes in adult subjects with acquired hemophilia A that required hospitalization were investigated in a prospective, open-label trial (N=29). Subjects with a prior history of bleeding disorders other than AHA, anti-porcine FVIII antibody titer >20 Bethesda Units (BU), or in whom the bleeding episode was judged likely to resolve on its own, were excluded. All subjects in the study received immunosuppressive therapy to treat their autoimmune disease. One subject was considered evaluable at study entry; however, it was later determined that this subject did not have AHA, leaving 28 subjects evaluable for efficacy. An initial dose of 200 units per kg OBIZUR was administered to subjects for the treatment of life- or limb-threatening initial bleeding episodes. Hemostatic response was assessed using a prespecified rating scale that was based on subjective clinical assessments combined with objective Factor VIII activity levels achieved. An assessment of effective or partially effective was considered as a positive response.
*Per an interventional, prospective, open-label clinical trial measuring the hemostatic response of OBIZUR at specified time points based on 1) a prespecified rating scale per clinical assessments and 2) objective FVIII activity levels achieved.1
†A positive response is one that was deemed to be either effective or partially effective; that is, bleeding stopped or reduced, with clinical improvement and achievement of specified FVIII trough levels.1
‡Determined by the investigator based on his/her ability to discontinue OBIZUR or reduce the dose and/or dosing frequency.
Indication
OBIZUR, Antihemophilic Factor (Recombinant), Porcine Sequence, is a recombinant DNA derived, antihemophilic factor indicated for the on-demand treatment and control of bleeding episodes in adults with acquired hemophilia A...
OBIZUR, Antihemophilic Factor (Recombinant), Porcine Sequence, is a recombinant DNA derived, antihemophilic factor indicated for the on-demand treatment and control of bleeding episodes in adults with acquired hemophilia A...
Detailed Important Risk Information
CONTRAINDICATIONS
OBIZUR is contraindicated in patients
- Who have had life-threatening hypersensitivity reactions to OBIZUR or its components (including traces of hamster proteins).
- With congenital hemophilia A with inhibitors due to the high incidence of anamnestic reactions to human factor VIII (hFVIII) and porcine factor VIII (pFVIII).
OBIZUR Important Information
Indication
OBIZUR, Antihemophilic Factor (Recombinant), Porcine Sequence, is a recombinant DNA derived, antihemophilic factor indicated for the on-demand treatment and control of bleeding episodes in adults with acquired hemophilia A.
Limitations of Use:
- Safety and efficacy of OBIZUR has not been established in patients with baseline anti-porcine factor VIII inhibitor titer greater than 20 BU
- OBIZUR is not indicated for the treatment of von Willebrand disease
Detailed Important Risk Information
CONTRAINDICATIONS
OBIZUR is contraindicated in patients
- Who have had life-threatening hypersensitivity reactions to OBIZUR or its components (including traces of hamster proteins).
- With congenital hemophilia A with inhibitors due to the high incidence of anamnestic reactions to human factor VIII (hFVIII) and porcine factor VIII (pFVIII).
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions can occur with OBIZUR. OBIZUR contains trace amounts of hamster proteins. Early signs of allergic reactions, which can progress to anaphylaxis, include angioedema, chest-tightness, dyspnea, hypotension, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if allergic or anaphylactic-type reactions occur.
Inhibitory Antibodies
Inhibitory antibodies to OBIZUR have occurred in patients treated with OBIZUR. Lack of efficacy could be due to inhibitory antibodies to OBIZUR.
Anamnestic reactions with rise in human factor VIII and/or recombinant factor VIII porcine sequence inhibitors have also been reported in patients treated with OBIZUR. These anamnestic rises also may result in a lack of efficacy.
Consider evaluating for presence of anti-recombinant porcine factor VIII (anti-rpFVIII) antibodies prior to initiation of treatment with OBIZUR. In instances where positive anti-rpFVIII antibody results are detected after treatment with OBIZUR is initiated, factor VIII levels may be used to decide whether treatment with OBIZUR should be continued.
Monitor patients for the development of antibodies to OBIZUR by appropriate assays. If the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled after OBIZUR administration, suspect the presence of an anti-porcine factor VIII antibody.
If such inhibitory antibodies are suspected and there is a lack of efficacy, consider management options such as discontinuing OBIZUR and initiating other therapeutics such as a factor VIII bypassing agent.
Monitoring Laboratory Tests
- Perform one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and maintained
- Monitor factor VIII activity 30 minutes and 3 hours after initial dose
- Monitor factor VIII activity 30 minutes after subsequent doses
- Monitor the development of inhibitory antibodies to OBIZUR. Perform a Nijmegen Bethesda inhibitor assay with recombinant porcine factor VIII as substrate for recombinant porcine factor VIII antibodies if expected plasma factor VIII activity levels are not attained or if bleeding is not controlled with the expected dose of OBIZUR. Use Bethesda Units (BU) to report inhibitor levels. Contact Takeda at 1-877-TAKEDA-7 (1-877-825-3327)1-877-TAKEDA-7 (1-877-825-3327) if additional information is needed regarding testing.
ADVERSE REACTIONS
Common adverse reactions observed in greater than 5% of subjects in the clinical trial were development of inhibitors to porcine factor VIII.
Please click here for OBIZUR full Prescribing Information
To report suspected adverse reactions, contact Takeda at 1-877-TAKEDA-7 (1-877-825-3327)1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-10881-800-FDA-1088 or www.fda.gov/medwatch