Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: CSL Behring GmbH, D-35041 Marburg, Germany
Hemgenix is indicated for the treatment of severe and moderately severe Haemophilia B (congenital Factor IX deficiency) in adult patients without a history of Factor IX inhibitors.
Treatment should be initiated under the supervision of a physician experienced in the treatment of Haemophilia and/or bleeding disorders. This medicinal product should be administered in a setting where personnel and equipment are immediately available to treat infusion related reactions (see sections 4.4 and 4.8).
Hemgenix should only be administered to patients who have demonstrated absence of Factor IX inhibitors. In case of a positive test result for human Factor IX inhibitors, a re-test within approximately 2 weeks should be performed. If both the initial test and re-test results are positive, the patient should not receive Hemgenix.
In addition, before administration of Hemgenix, baseline testing of liver health and assessment of preexisting neutralising anti-AAV5 antibody titre should be performed; see section 4.4.
The recommended dose of Hemgenix is a single dose of 2 × 1013 gc/kg body weight corresponding to 2 mL/kg body weight, administered as an intravenous infusion after dilution with sodium chloride 9 mg/mL (0.9%) solution for injection (see section 4.2 below and section 6.6).
Hemgenix can be administered only once.
The onset of effect from etranacogene dezaparvovec treatment may occur within several weeks post-dose (see section 5.1). Therefore, haemostatic support with exogenous human Factor IX may be needed during the first weeks after etranacogene dezaparvovec infusion to provide sufficient Factor IX coverage for the initial days post-treatment. Monitoring of the Factor IX activity (e.g. weekly for 3 months) is recommended post-dose to follow the patient’s response to etranacogene dezaparvovec.
When using an in vitro activated partial thromboplastin time (aPTT)-based one-stage clotting assay for determining Factor IX activity in patients' blood samples, plasma Factor IX activity results can be affected by both the type of aPTT reagent and the reference standard used in the assay. This is important to consider particularly when changing the laboratory and/or reagents used in the assay (see section 4.4). Therefore the same assay and reagents are recommended to be used to monitor Factor IX activity over time.
In case increased plasma Factor IX activity levels are not achieved, decrease, or bleeding is not controlled or returns, post-dose testing for Factor IX inhibitors is recommended along with Factor IX activity testing.
No dose adjustments are recommended in elderly patients. Limited data are available in patients aged 65 years and older (see section 5.1).
No dose adjustments are recommended in patients with any level of renal impairment.
The safety and efficacy of etranacogene dezaparvovec in patients with severe renal impairment and endstage renal disease have not been studied (see section 5.2).
No dose adjustments are recommended in patients with hepatic disorders (see sections 4.3 and 5.2).
The safety and efficacy of etranacogene dezaparvovec in patients with severe hepatic impairment have not been studied. Etranacogene dezaparvovec is contraindicated in patients with acute or uncontrolled chronic hepatic infections, or in patients with known advanced liver fibrosis, or cirrhosis (see section 4.3). This medicinal product is not recommended for use in patients with other significant hepatic disorders (see sections 4.4 and 5.2).
No dose adjustments are recommended in HIV-positive patients. Limited data are available in patients with controlled HIV infection.
The safety and efficacy of etranacogene dezaparvovec in children aged 0 to 18 years have not been studied. No data are available.
Hemgenix is administered as a single-dose intravenous infusion after dilution of the required dose with sodium chloride 9 mg/mL (0.9%) solution for infusion. Etranacogene dezaparvovec must not be administered as an intravenous push or bolus.
For instructions on dilution of the product prior to administration, see section 6.6.
The diluted product should be administered at a constant infusion rate of 500 mL/hour (8 mL/min).
For detailed instructions on preparation, handling, measures to take in case of accidental exposure and disposal of Hemgenix, see section 6.6.
There are no clinical study data regarding overdose with etranacogene dezaparvovec.
24 months.
After dilution:
Once diluted with sodium chloride 9 mg/mL (0.9%) solution for injection (see section 6.6), Hemgenix can be stored at 15°C-25°C in the infusion bag protected from light. However, the administration of etranacogene dezaparvovec dose to the patient should be completed within 24 hours after the dose preparation.
The stability after dilution was established for Polyethylene/Polypropylene (PE/PP) copolymer, Polyvinyl chloride (PVC)-free infusion bags with sodium chloride 9 mg/mL (0.9%) solution for injection.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Store in the original package in order to protect from light.
Dilute before use.
For storage conditions after dilution of the medicinal product, see section 6.3.
10 mL solution in a Type I glass vial with stopper (chlorobutyl rubber), aluminium seal with a flip-off cap.
Hemgenix is supplied in a vial containing 10 mL.
The total number of vials in each finished pack corresponds to the dosing requirement of the individual patient, depending on the body weight, and is provided on the package.
Precautions to be taken before handling or administering the medicinal product:
This medicinal product contains genetically modified organisms (GMOs). Personal protective equipment, including gloves, safety goggles, protective clothing and masks, should be worn while preparing and administering etranacogene dezaparvovec.
Preparation of etranacogene dezaparvovec prior to administration:
1. Use aseptic techniques during the preparation and administration of etranacogene dezaparvovec.
2. Use etranacogene dezaparvovec vial(s) only once (single-use vial(s)).
3. Verify the required dose of etranacogene dezaparvovec based on the patient’s body weight. The total number of vials in each finished pack corresponds to the dosing requirement for each individual patient based on the body weight.
4. Etranacogene dezaparvovec must be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection prior to administration.
5. Add the Hemgenix dose directly into the sodium chloride 9 mg/mL (0.9%) solution for injection. Do not add the Hemgenix dose into the air in the infusion bag during diluting.
6. Gently invert the infusion bag(s) at least 3 times to mix the solution and ensure even distribution of the diluted product.
7. To avoid foaming:
8. To reduce the risk of spillage and/or aerosol formation, the infusion bag(s) should be provided connected to an infusion tubing prefilled with sterile sodium chloride 9 mg/mL (0.9%) solution for injection.
9. The infusion tubing prefilled with sterile sodium chloride 9 mg/mL (0.9%) solution for injection should be connected to the main intravenous infusion line also primed with sterile sodium chloride 9 mg/mL (0.9%) solution for injection prior to use.
10. Use only sodium chloride 9 mg/mL (0.9%) solution for injection since the stability of etranacogene dezaparvovec has not been determined with other solutions and diluents.
11. Do not infuse the diluted etranacogene dezaparvovec solution in the same intravenous line with any other products.
12. Do not use a central line or port.
Administration:
13. Diluted etranacogene dezaparvovec should be visually inspected prior to administration. The diluted etranacogene dezaparvovec should be a clear, colourless solution. If particulates, cloudiness or discoloration are visible in the infusion bag, do not use etranacogene dezaparvovec.
14. Use the product after dilution as soon as possible. You must not exceed the storage time of the diluted product beyond that provided section 6.3.
15. Use an integrated (in-line) 0.2 µm filter made out of polyethersulfone (PES).
16. The diluted etranacogene dezaparvovec solution must be administered into a peripheral vein by a separate intravenous infusion line through a peripheral venous catheter.
17. Etranacogene dezaparvovec solution should be infused closely following the infusion rate(s) provided in section 4.2. The administration should be completed within ≤24 hours after the dose preparation (see section 4.2).
18. After the entire content of the infusion bag(s) is infused, the infusion line must be flushed at the same infusion rate with sodium chloride 9 mg/mL (0.9%) solution for injection to ensure all etranacogene dezaparvovec is delivered.
Measures to take in case of accidental exposure:
In case of accidental exposure local guidance for pharmaceutical waste must be followed.
Work surfaces and materials which have potentially been in contact with etranacogene dezaparvovec must be decontaminated with appropriate disinfectant with viricidal activity (e.g. a chlorine releasing disinfectant like hypochlorite containing 0.1% available chlorine (1000 ppm)) after usage.
Precautions to be taken for the disposal of the medicinal product:
Unused medicinal product and disposable materials that may have come in contact with Hemgenix (solid and liquid waste) must be disposed of in compliance with the local guidance for pharmaceutical waste. Caregivers should be advised on the proper handling of waste material generated from contaminated medicinal ancillaries during Hemgenix use.
Work surfaces and materials which have potentially been in contact with etranacogene dezaparvovec must be decontaminated with appropriate disinfectant with viricidal activity (e.g. a chlorine releasing disinfectant like hypochlorite containing 0.1% available chlorine (1000 ppm)) after usage and then autoclaved, if possible.
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