Consumer medicine information

Obizur

Susoctocog alfa

BRAND INFORMATION

Brand name

Obizur

Active ingredient

Susoctocog alfa

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Obizur.

What is in this leaflet

Read this leaflet carefully before you start using OBIZUR.

This leaflet answers some common questions about OBIZUR. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of using your medicine against the benefit that it will have for you.

If you have any concerns about having this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What OBIZUR is used for

OBIZUR is a recombinant DNA derived, anti-haemophilic factor used for the treatment of bleeding episodes in adults with acquired haemophilia A.

It is possible that your doctor may give you OBIZUR for another reason.

Ask your doctor if you have any questions about why you are being given OBIZUR.

How does OBIZUR work

Under normal physiological conditions, factor VIII is essential for blood clotting and therefore the control of bleeding.

Acquired haemophilia is a bleeding disorder that is not present at birth but develops suddenly at some point in life due to an abnormality in the immune system. In patients with acquired haemophilia A, factor VIII is not working properly because the patient has developed antibodies which neutralise this blood clotting factor, and this prevents blood from clotting.

OBIZUR belongs to a group of medicines called anti-haemophilic agents.

OBIZUR is a man-made clotting factor. It is similar to the naturally occurring protein in the body.

OBIZUR works by temporarily replacing the inhibited human clotting factor VIII, so that blood can clot normally.

Before you are given OBIZUR

When you must not be given OBIZUR

OBIZUR should not be given to you if you are:

  • allergic to any products of porcine or hamster origin;.
  • allergic to any ingredients in this product which are listed at the end of the leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath, wheezing or difficulty breathing;
  • swelling of the face, lips, tongue or other parts of the body;
  • rash, itching or hives on the skin

If you are not sure, talk to your doctor before using OBIZUR.

Do not use this medicine in children. The safety and effectiveness in children have not been established.

Do not use this medicine if the expiry date printed on the pack has passed or if the packaging shows sign of tampering.

Before you are given OBIZUR

You should tell your doctor if you:

  • have or have had any medical problems;
  • have any allergies, including allergies to products that are of porcine or hamster origin;
  • have had heart problems or blood clot in the past or you have any other conditions that make you at risk of developing blood clots;
  • are on a controlled sodium diet;
  • are breast feeding (it is not known if OBIZUR passes into your milk and if it can harm your baby);
  • are pregnant or planning to become pregnant (it is not known if OBIZUR may harm your unborn baby).

If you are breast feeding or if you are pregnant or planning to have a baby, ask your doctor for advice before using OBIZUR.

Taking other medicines

Tell your doctor or pharmacist if you are using any other medicines including any that you obtained without a prescription from your pharmacy, supermarket or health food shop.

Your doctor or pharmacist has more information on medicines to be careful with or to avoid while being given OBIZUR.

How OBIZUR is given

How much is given

Your doctor will decide the dose of OBIZUR you will receive. Each individual will receive a different amount, which may vary between treatments.

The dose you receive will be based on:

  • body weight;
  • your condition, e.g. in which sites the bleeding occurs (knees, muscle, etc.).

As a general guide, an initial first dose of 200 U per kilogram (U/kg) bodyweight is recommended.

The frequency and duration of treatment will depend on how well OBIZUR is working for you. Your doctor will adjust the dose and frequency of OBIZUR injections until the bleeding stopped.

How OBIZUR is given

OBIZUR is usually given in a hospital so that you are under the care of a healthcare professional.

OBIZUR is given by a slow injection directly into your vein.

Use aseptic technique to prepare OBIZUR for injection.

Use only the water for injections supplied with the pack to prepare OBIZUR for injection.

Do not mix OBIZUR with any other medicines or solvent.

Always inspect the solution after it is prepared for use and before injection. The solution should be clear and colourless.

Do not inject if the solution is discoloured or cloudy or contains particles.

Use the solution straight away or within 3 hours after it is prepared.

Do not refrigerate the solution after it is prepared.

Use a new syringe and needle for each injection.

Do not mix OBIZUR with other medicines.

If you are given too much (overdose)

As OBIZUR will be given to you by a doctor/nurse, it is unlikely that you will be given an overdose.

Your healthcare professional will regularly monitor your condition and test your blood to prevent overdose.

Immediately telephone your doctor or the National Poisons Information (telephone 131 126), or go to accident and emergency at your nearest hospital, if you think that you or anyone else may have been given too much OBIZUR.

Do this even if there are no signs of discomfort or poisoning.

While you are using OBIZUR

Things you must do

You will have your blood tested after the initial OBIZUR injection and also regularly after subsequent injections to see how your treatment is working. This is to check your blood level of factor VIII to confirm that you have received adequate treatment. Your doctor will also check if the bleeding is adequately controlled.

Your doctor may do additional blood tests to check if you have developed antibodies to OBIZUR treatment.

Monitor your bleeding and tell your doctor or nurse if your bleeding gets worse.

Tell your doctor or pharmacist immediately if you experience any of the following during the OBIZUR injection:

  • shortness of breath; wheezing; difficulty breathing; chest pain or discomfort;
  • changes in facial skin colour, puffiness or swelling of your face, lips, tongue, or other parts of the body, rash or hives.

The above list includes signs and symptoms of a severe allergic response to the medicine. The use of OBIZUR should be stopped immediately if any of the above occurs during injection.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well after using OBIZUR.

All medicines can have side effects. Sometimes they are serious, most of the time they are not.

You may need medical attention if you get some of these side effects.

Do not be alarmed by this list of possible side effects, you may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

The following list includes the common side effects for OBIZUR:

  • antibodies against OBIZUR detected in blood test results.

A rapid increased production of antibodies in response to subsequent treatment with OBIZUR have also been reported.

Tell your doctor or pharmacist of any suspected undesirable effect that is not mentioned in this leaflet.

Other side effects not listed above may occur in some patients.

After using OBIZUR

Storage

Keep out of the reach and sight of children.

Store OBIZUR at 2°C - 8°C in a refrigerator. Do not freeze.

Keep OBIZUR in the pack until it is time to use it. This will protect the vials from light. If the vials are not stored in the pack, the product may not keep well.

Do not store the solution in the fridge after the powder is mixed with the diluent.

Disposal

OBIZUR is for single use in single patient only.

Discard any unused solution left in the vial at the end of your infusion.

Dispose the used vials and all materials in an appropriate container. Medicines should not be disposed of via wastewater or household waste. These measures will help to protect the environment.

If your doctor tells you to stop using OBIZUR or the expiry date has passed, ask your pharmacist or your Haemophilia Treatment Centre what to do with any medicine that is left over.

Ask your doctor, pharmacist or Haemophilia Treatment Centre if you have any questions about how to dispose OBIZUR.

Product Description

What OBIZUR looks like

OBIZUR is a white powder supplied in a glass vial with a diluent prefilled syringe for reconstitution.

After reconstitution, the solution is clear, colourless and free from foreign particles.

OBIZUR is packed in cartons of 1, 5 and 10 single-packs.

Each single pack contains:

  • 1 vial of OBIZUR powder for injection;
  • 1 prefilled syringe of water for injections (used as the diluent to dissolve the OBIZUR powder);
  • 1 vial adapter (to help with transferring the diluent to prepare the solution for injection).

Not all pack sizes may be marketed.

Ingredients

Active ingredient:

  • susoctocog alfa.

Inactive ingredients:

  • sodium chloride;
  • sucrose;
  • sodium citrate dihydrate;
  • calcium chloride dihydrate;
  • trometamol;
  • water for injections (diluent).

Sponsor

OBIZUR is supplied in Australia by:

Takeda Pharmaceuticals Australia Pty Ltd
Level 39
225 George Street
Sydney NSW 2000
Australia
Telephone: 1800 012 612
www.takeda.com/en-au

Australian registration numbers

AUST R 236475

Date of preparation

This leaflet was prepared in
November 2020.

OBIZUR® is a registered trademark of Baxalta Incorporated.

TAKEDA® and the TAKEDA Logo® are registered trademarks of Takeda Pharmaceutical Company Limited.

Published by MIMS January 2021

BRAND INFORMATION

Brand name

Obizur

Active ingredient

Susoctocog alfa

Schedule

Unscheduled

 

1 Name of Medicine

Susoctocog alfa (bhk).

2 Qualitative and Quantitative Composition

Each Obizur vial contains nominally 500 units (U) of susoctocog alfa, which is a B domain deleted recombinant derived antihaemophilic factor VIII (rpFVIII), porcine sequence.
After reconstitution, Obizur contains nominally 500 U/mL susoctocog alfa.
Each vial of Obizur is labelled with the actual rpFVIII activity expressed in units determined by a one stage clotting assay, using a reference rpFVIII material calibrated against the World Health Organization (WHO) 8th International Standard for human factor VIII concentrates. The specific activity of Obizur is in the range of 11,000-18,000 units per milligram of protein. The potency values of Obizur determined by the chromogenic assay vary and are approximately 20-50% lower than those of the one-stage clotting assay.
Susoctocog alfa is expressed in a genetically engineered baby hamster kidney (BHK) cell line and secreted into the cell culture medium, and the protein is purified using a series of chromatography and filtration steps. The production process includes two dedicated viral clearance steps - a solvent/detergent treatment step for viral inactivation and a nanofiltration step through a series of two 15 nanometre filters for removal of viruses. No additives of human or animal origin are used in the formulation of Obizur.

Excipient(s) with known effect.

Each vial of Obizur contains maximally 4.4 mg (198 mM) sodium per mL of reconstituted solution (see Section 4.4 Special Warnings and Precautions for Use).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder and diluent for solution for injection.
Obizur is formulated as a white, sterile, non-pyrogenic, lyophilised powder for intravenous injection after reconstitution with the diluent.
The diluent, water for injections, is a clear and colourless solution, practically free from visible particles.

4 Clinical Particulars

4.1 Therapeutic Indications

Obizur, antihaemophilic factor (recombinant), porcine sequence, is a recombinant DNA derived, antihaemophilic factor indicated for the treatment of bleeding episodes in adults with acquired haemophilia A.
Safety and efficacy of Obizur have not been established in patients with baseline anti-porcine factor VIII inhibitor titre greater than 20 Bethesda Units (BU).
Obizur is not indicated for the treatment of congenital haemophilia A or von Willebrand disease.

4.2 Dose and Method of Administration

Treatment with Obizur under the supervision of a physician experienced in the treatment of bleeding disorders is recommended.
For prescribed doses of Obizur, "units" should be written in full.
The product is for single use in one patient only. Discard any residue.
Dosage, frequency, and duration of treatment with Obizur depends on the severity of bleeding episode, target factor VIII levels, and the patient's clinical condition.
Parenteral drug products should be inspected for particulate matter and discolouration prior to administration. Do not administer if particulate matter or discoloration is found; contact Takeda Customer Service.

Dose.

Dose, dosing frequency, and duration of treatment with Obizur depend on the location and severity of bleeding episode, target factor VIII levels, and the patient's clinical condition. Monitor replacement therapy in cases of major surgery or life-threatening bleeding episodes.
Each vial of Obizur has the recombinant porcine factor VIII potency in units stated on the vial.
Patients may vary in their pharmacokinetic (e.g. half-life, in vivo recovery) and clinical responses. Titrate dose and frequency based on factor VIII recovery levels and individual clinical response.
A guide for dosing Obizur for the treatment of bleeding episodes is provided in Table 1. Maintain the factor VIII activity within the target range. Plasma levels of factor VIII should not exceed 200% of normal or 200 units per dL.

Reconstitution.

Use aseptic technique during the reconstitution procedure.
If the patient needs more than one vial of Obizur per injection, reconstitute each vial according to the following instructions:
1. Bring the Obizur vial and the prefilled diluent syringe to room temperature.
2. Remove the plastic cap from the Obizur vial.
3. Wipe the rubber stopper with an alcohol swab (not supplied) and allow it to dry prior to use.
4. Peel back the cover of the vial adapter package. Do not touch the luer-lock (tip) in the center of the vial adapter. Do not remove the vial adapter from the plastic package.
5. Place the vial adapter package on a clean surface with the luer-lock pointing up.
6. Snap off the tamper resistant cap of the prefilled syringe.
7. While firmly holding the vial adapter package, connect the prefilled syringe to the vial adapter by pushing the syringe tip down onto the luer lock in the center of the vial adapter, and turning it clockwise until the syringe is secured. Do not over tighten.
8. Remove the plastic package.
9. Place the Obizur vial on a clean, flat, hard surface. Place the vial adapter over the Obizur vial and firmly push the filter spike of the vial adapter through the center of the rubber circle until the clear plastic cap snaps onto the vial.
10. Push the plunger down to slowly inject all of the diluent from the syringe into the Obizur vial.
11. Gently swirl (in a circular motion) the Obizur vial without removing the syringe until all of the powder is fully dissolved. The reconstituted solution should be inspected visually for particulate matter before administration. Do not use if particulate matter or discoloration is observed.
12. With one hand hold the vial and vial adapter, and with the other hand firmly grasp the barrel of the prefilled syringe and in a counterclockwise motion unscrew the syringe from the vial adapter.
13. Use Obizur within 3 hours after reconstitution when stored at room temperature.

Administration.

For intravenous injection only.
Inspect the reconstituted Obizur solution for particulate matter and discoloration prior to administration. The solution should be clear and colourless in appearance. Do not administer if particulate matter or discolouration is observed.
Do not administer Obizur in the same tubing or container with other medicinal products for infusion.
1. Once all vials have been reconstituted, connect a large syringe to the vial adapter by gently pushing the syringe tip down onto the luer-lock in the center of the vial adapter, and turning clockwise until the syringe is secured.
2. Invert the vial; push the air in the syringe into the vial and withdraw the reconstituted Obizur into the syringe.
3. Unscrew the large syringe counterclockwise from the vial adapter, and repeat this process for all reconstituted vials of Obizur until the total volume to be administered is reached.
4. Administer the reconstituted Obizur intravenously at a rate of 1 to 2 mL per minute.

4.3 Contraindications

Obizur is contraindicated in:
patients who have had life-threatening hypersensitivity reactions to Obizur or its components (including traces of hamster proteins);
congenital haemophilia A with inhibitors (CHAWI), see Section 4.8 Adverse Effects (Undesirable Effects), Immunogenicity.

4.4 Special Warnings and Precautions for Use

Initial dosing below the recommended 200 U/kg has been associated with lack of efficacy. (See Section 4.2 Dose and Method of Administration.)

Hypersensitivity reactions.

Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the injection site, chills, flushing, generalised urticarial, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) are possible and may progress to severe anaphylaxis (including shock).
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 may result in lack of response to Obizur.
It is recommended to test for anti-rpFVIII antibodies prior to initiation of treatment with Obizur. Treatment may be started at physician's discretion prior to receiving the result of this test. Treatment decisions can be further supported by monitoring factor VIII levels.
Monitor patients for the development of antibodies to Obizur by appropriate assays (see Section 4.8 Adverse Effects (Undesirable Effects)). 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 to porcine factor VIII are suspected and there is a lack of clinical response, consider other therapeutic options.

Monitoring laboratory tests.

Perform one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and maintained (see Section 4.2 Dose and Method of Administration).
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 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.

Others.

High and sustained factor VIII activity in blood may predispose to thromboembolic events. Those with pre-existing cardiovascular disease and the elderly are at particular risk.
Obizur contains maximally 4.4 mg (198 mM) sodium per 500 unit (nominal) vial. This should be taken into consideration by patients on a controlled sodium diet.

Use in the elderly.

Of the 29 subjects within the trial, the average age was 70 years of age. Nineteen subjects were 65 years of age or older. Clinical studies suggest that Obizur is safe and effective in the adult population (see Section 4.8 Adverse Effects (Undesirable Effects); Section 5.1 Pharmacodynamic Properties, Clinical trials). While no differences were observed between geriatric and adult responses to Obizur, these findings are inconclusive given the small number of subjects enrolled in either group.
Dose adjustments in the geriatric population have not been studied. Specific hazards associated with the concomitant use of Obizur with other drugs in the elderly population have not been studied in the clinical trial.

Paediatric use.

The safety and efficacy of Obizur have not been established in paediatric patients.
Use in children [from 0 (birth) to < 18 years] with congenital or in rare cases acquired haemophilia is currently not approved, also see Section 4.3 Contraindications.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions of Obizur with other medicinal products are known.
No interaction studies have been performed with Obizur. Further, no interactions of Obizur with other medicinal products have been reported.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effects of Obizur on fertility have not been established.
(Category B2)
There are no adequate or well-controlled studies with Obizur, or other recombinant factor VIII products, in pregnant women. Studies in pregnant animals have not been conducted with susoctocog alfa. Therefore, Obizur should only be used in pregnant women if clearly needed.
 It is not known whether Obizur is excreted into human milk. Because many drugs are excreted into human milk, caution should be exercised if Obizur is administered to breastfeeding mothers.

4.7 Effects on Ability to Drive and Use Machines

There is no information of the effects of Obizur on the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions from clinical trials.

In the clinical trial of Obizur for acquired haemophilia A, 29 adult subjects were evaluable for safety. Of the 29 adult subjects, ten were between the ages of 42 and 65, and 19 were 65 years of age or older. Ten (34%) subjects were female.
In the clinical trial, serious adverse drug reactions (ADRs) occurred in 9 subjects. Two subjects (6.9%) developed anti-porcine factor VIII inhibitors (> 0.6 BU) that were considered an adverse reaction (AR) to Obizur by the investigator. Seven subjects (24.1%) developed anamnestic reactions with a rise ≥ 10 BU in human factor VIII and/or recombinant factor VIII, porcine sequence inhibitors. See Table 2.

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 titre was ≥ 0.6 BU/mL.
Of the 29 subjects treated with Obizur, 19 subjects did not have a detectable anti-porcine factor VIII inhibitor titer at baseline (< 0.6 BU/mL). Of the 19 subjects, 12 subjects had no detectable anti-porcine factor VIII titer post-treatment, 5 subjects had an increase in titer (≥ 0.6 BU/mL), and 2 subjects had no post-treatment samples analysed. Seven subjects developed anamnestic reactions with a rise ≥ 10 BU/mL in human factor VIII and/or recombinant factor VIII, porcine sequence inhibitors. Of the 10 subjects with detectable anti-porcine factor VIII inhibitor titer at baseline, which can be considered to be cross reactive with anti-human factor VIII inhibitors, 8 subjects had no detectable anti-porcine factor VIII titer post-treatment (< 0.6 BU/mL based on the last reported result), 2 subjects experienced an increase in titre (≥ 0.6 BU/mL).
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 neutralising 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.
In the clinical study of Obizur in patients with congenital haemophilia A with factor VIII inhibitors (CHAWI) undergoing surgery, out of 8 adult patients evaluable for safety analysis a total of 5 subjects experienced anamnestic reactions.

Post-marketing adverse reactions.

No adverse reactions other than those reported during clinical trials have been observed in the post-marketing setting.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

No symptoms of overdose have been reported.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor VIII, porcine sequence.
ATC code: B02BD14.

Mechanism of action.

Patients with acquired haemophilia A have normal factor VIII genes but develop auto-antibodies against their own factor VIII (i.e. inhibitors). These auto-antibodies neutralise circulating human factor VIII and create a functional deficiency of this pro-coagulant protein. Acquired haemophilia A 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 normalise the aPTT during treatment; however aPTT normalisation should not be used as a measure of efficacy. Once susoctocog alfa is activated, the resulting molecule has a comparable activity to the endogenous human activated factor VIII.

Clinical trials.

The efficacy of Obizur for the treatment of serious bleeding episodes in subjects with acquired haemophilia 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 haemophilia A, having auto-immune inhibitory antibodies to human factor VIII, and experiencing serious bleeding episodes that required hospitalisation. Subjects with a prior history of bleeding disorders other than acquired haemophilia A, anti-porcine factor VIII antibody titre > 20 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 acquired haemophilia A, 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 postsurgical bleeding episodes, 2 intracranial episodes, 2 surgeries, 1 retroperitoneal haemorrhage, and 1 periorbital bleed. Haemostatic 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 3 for definitions).
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 antihaemorrhagic agents prior to the first Obizur treatment, 16/17 (94%) had eventual treatment success reported. Eleven subjects were reported to have received antihaemorrhagics (e.g. 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 utilised 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.

5.2 Pharmacokinetic Properties

Pharmacokinetic (PK) data on Obizur are limited and were obtained from 5 subjects in a safety and efficacy study of Obizur for the treatment of serious bleeding episodes in subjects with acquired haemophilia with autoimmune inhibitory antibodies to human factor VIII was investigated in a prospective, open-label trial (N = 29). The trial was conducted in 18 Caucasian, African-American, and 5 Asian subject(s) experiencing serious bleeding requiring hospitalisation.
All blood draws were done while the subject was in a non-bleeding state. For each subject t1/2, Tmax, Amax, AUC from time 0 to last measurement (AUC0-t), AUC0-inf, CL, and the volume of distribution at steady state are presented. Mean values for each parameter are also presented.
For the final dose PK analysis, the % relative factor VIII activity data from the one-stage assays are presented as baseline-corrected values. The individual and summary PK parameters are presented in Table 4.
The summary parameters indicate a maximal activity of Obizur (Tmax) at about 26 minutes, with a mean terminal half time (t1/2) of 3.5 hours after dosing. The data are consistent with Obizur following first order elimination.

5.3 Preclinical Safety Data

Genotoxicity.

Genotoxicity studies have not been conducted which is acceptable for a biotechnology-derived product such as Obizur.

Carcinogenicity.

Carcinogenicity studies have not been conducted which is acceptable for a biotechnology derived product such as Obizur.

6 Pharmaceutical Particulars

6.1 List of Excipients

Polysorbate 80, sodium chloride, calcium chloride dihydrate, sucrose, trometamol, sodium citrate dihydrate, water for injections (diluent).

6.2 Incompatibilities

Incompatibility studies have not been performed with Obizur. In the absence of compatibility studies with Obizur, this medicinal product should not be mixed with other medicinal products.

6.3 Shelf Life

3 years.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C-8°C). Do not freeze.
Do not use beyond the expiration date.

Storage after reconstitution.

The reconstituted product should be used immediately, but no longer than 3 hours after reconstitution.

6.5 Nature and Contents of Container

Each pack of Obizur contains 1, 5 or 10 each of the following:
powder vial(s) of 500 units susoctocog alfa;
diluent prefilled syringe(s) of 1 mL water for injections;
vial adapter(s) with filter.
Both the powder vial and the diluent prefilled syringe are supplied in type 1 glass with butyl rubber stopper.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Susoctocog alfa is a purified glycoprotein with an approximate molecular weight of 170 kDa, containing a 90 kDa heavy chain and a 80 kDa light chain. The B-domain normally present in naturally occurring porcine factor VIII has been replaced with a twenty-four amino acid linker.

CAS number.

1339940-90-7.

7 Medicine Schedule (Poisons Standard)

Unscheduled (Exempted).

Summary Table of Changes