Obizur

Antihemophilic factor (AHF) recombinant porcine sequence injection is used to treat serious bleeding episodes in patients with acquired hemophilia A. The bleeding episode may be due to an injury or surgery. Antihemophilic factor recombinant porcine sequence is a manmade protein to replace the AHF produced naturally in the body to help form blood clots to stop bleeding.

Acquired Hemophilia A, also called classic hemophilia, is a condition that develops where the body does not make enough AHF. If you do not have enough AHF and you become injured, your blood will not form clots properly. You might bleed into and damage your muscles and joints. AHF injection is given to increase the levels of AHF in the blood.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

• Powder for Solution

Mechanism Of Action

OBIZUR temporarily replaces the inhibited endogenous factor VIII that is needed for effective hemostasis in patients with acquired hemophilia A.

Pharmacodynamics

Patients with acquired hemophilia A (AHA) have normal factor VIII genes but develop autoantibodies against their own factor VIII (i.e., inhibitors). These autoantibodies neutralize circulating human factor VIII and create a functional deficiency of this procoagulant protein. AHA results in a prolonged clotting time as measured by the activated partial thromboplastin time (aPTT) assay, a conventional In vitro test for biological activity of factor VIII. Treatment with OBIZUR should normalize the aPTT during treatment; however aPTT normalization should not be used as a measure of efficacy.

Clinical Studies

The efficacy of OBIZUR for the treatment of serious bleeding episodes in subjects with acquired hemophilia A was investigated in a prospective, open-label trial (N=29). The trial was conducted in 18 Caucasian, 6 African-American, and 5 Asian subjects diagnosed with acquired hemophilia A (AHA), having auto-immune inhibitory antibodies to human factor VIII, and experiencing serious bleeding episodes that required hospitalization. Subjects with a prior history of bleeding disorders other than AHA, anti-porcine factor VIII antibody titer > 20 Bethesda Units (BU), or in whom the bleeding episode was judged likely to resolve on its own were excluded. 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. Patients were treated with OBIZUR until resolution of bleeding or dosing was continued at the physician's discretion according to the clinical assessment. These bleeding episodes included 19 intramuscular or joint bleeding episodes, 4 post-surgical bleeding episodes, 2 intracranial episodes, 2 surgeries, 1 retroperitoneal hemorrhage, and 1 periorbital bleed. Hemostatic response was assessed by the study site investigator at specified time points after initiation of OBIZUR treatment using a pre-specified 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 (see Table 2 for definitions).

Table 2 : Response to OBIZUR Treatment Evaluation

Of the 28 subjects evaluable for efficacy, all subjects had a positive response to treatment for the initial bleeding episodes at 24 hours after dosing. A positive response was observed in 95% (19/20) of subjects evaluated at 8 hours and 100% (18/18) at 16 hours.

In addition to response to treatment, the overall treatment success was determined by the investigator based on his/her ability to discontinue or reduce the dose and/or dosing frequency of OBIZUR. A total of 24/28 (86%) had successful treatment of the initial bleeding episode. Of those subjects treated with OBIZUR as first-line therapy, defined as no immediate previous use of anti-hemorrhagic agents prior to the first OBIZUR treatment, 16/17 (94%) had eventual treatment success reported. Eleven subjects were reported to have received anti-hemorrhagics (eg. rFVIIa, activated prothrombin-complex concentrate, tranexamic acid) prior to first treatment with OBIZUR. Of these 11 subjects, eight had eventual successful treatment (73%).

The median dose per infusion to successfully treat the primary bleeding episode was 133 units per kg and a median total dose of 1523 units per kg. In the initial 24 hour period, a median of 3 infusions (median dose 200 U/kg) were utilized in the clinical study. When treatment was required beyond 24 hours, a median of 10.5 infusions (median dose 100 U/kg) were given for a median of 6 days to control a bleeding episode.

Common adverse reactions observed in greater than 5% of subjects in the clinical trial were development of inhibitors to porcine factor VIII.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction (AR) rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety and efficacy of OBIZUR was evaluated in a multi-center, prospective, open-label, clinical trial that investigated adult patients with acquired hemophilia A. Twenty-nine adult subjects were enrolled in the study, received at least one dose of OBIZUR and were evaluable for safety [see Clinical Studies]. Of the 29 adult subjects, 10 were between the ages of 40 and 65, and 19 were 65 years of age or older (18 Caucasian, 6 African-American, and 5 Asian). Ten (34%) subjects were female.

The most frequently reported adverse reaction in patients with acquired hemophilia A was the development of inhibitors to porcine factor VIII.

Immunogenicity

All subjects were monitored for development of inhibitory antibodies to OBIZUR using the Nijmegen modification of the Bethesda inhibitor assay. A subject was considered to have developed an OBIZUR inhibitor if the titer was ≥ 0.6 Bethesda Units (BU)/mL.

Of the 29 subjects treated with OBIZUR, 19 subjects were negative for anti-porcine factor VIII antibodies at baseline. Five of the 19 (26%) developed anti-porcine factor VIII antibodies following exposure to OBIZUR. Of the 10 subjects with detectable anti-porcine factor VIII antibodies at baseline, 2 (20%) experienced an increase in titer and eight (80%) experienced a decreasing to a non-detectable titer.

All subjects were also monitored for development of binding antibodies to baby hamster kidney (BHK) protein by a validated sequential ELISA (enzyme-linked immunosorbent assay). No patients developed de novo anti-BHK antibodies.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to OBIZUR with the incidence of antibodies to other products may be misleading.

Read the entire FDA prescribing information for Obizur (Antihemophilic Factor (Recombinant), Porcine Sequence] Powder for Intravenous Injection)

Obizur is a prescription medication used to treat bleeding episodes in adults with acquired hemophilia A (acquired Factor VIII [FVIII] deficiency).

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Obizur falls into category C. No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Obizur should be given to a pregnant woman only if clearly needed.

Take Obizur exactly as prescribed.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional. Dose and frequency will be adjusted on the basis of the severity and location of acute bleeding episodes and patient’s clinical condition.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight

The dose and frequency of Obizur will be adjusted on the basis of the severity and location of acute bleeding episodes and patient’s clinical condition.

• Store Obizur at refrigeration temperature of 2° to 8°C [36° to 46°F]. Do not freeze.
• Store vials in the original package to protect from light.
• Do not use beyond the expiration date printed on the carton or vial.
• Use Obizur within 3 hours after reconstitution. Discard any unused reconstituted product if not used within 3 hours after reconstitution.
• Do not use Obizur if the reconstituted solution is cloudy or has particulate matter.

• If you have an allergy to Obizur (antihemophilic factor (recombinant [porcine sequence])) or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are allergic to hamsters, talk with the doctor.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Obizur with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.