BEQVEZ Concentrate for solution for infusion Ref.[113529] Active ingredients: Fidanacogene elaparvovec

Treatment should be administered in a qualified treatment centre by a physician experienced in the treatment of haemophilia. It is recommended that this medicinal product is administered in a setting where personnel and equipment are available to treat possible infusion-related reactions (see section 4.4).

A prophylactic dose of factor IX replacement should be given prior to fidanacogene elaparvovec infusion (see section 4.4).

Patient selection

Eligibility for treatment should be confirmed within 8 weeks prior to infusion by the following test results:

• negative for AAVRh74var pre-existing antibodies should be assessed by a CE-marked in vitro diagnostic (IVD) with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used.
• absence of clinically significant liver disease (see sections 4.3 and 4.4).
• negative for factor IX inhibitors by history and test <0.6 Bethesda Units (BU).
• absence of active infections, either acute (such as acute respiratory infections or acute hepatitis) or uncontrolled chronic (such as active chronic hepatitis B, hepatitis C, or human immunodeficiency virus infection [HIV]) (see section 4.3).

Posology

The recommended dose of BEQVEZ is a single-dose of 5 × 10¹¹ vector genomes per kg (vg/kg) of body weight.

To determine the patient’s dose, the following calculation steps are needed:

Calculation of patient’s dose weight:

The dose of BEQVEZ is based on the patient’s body mass index (BMI) in kg/m².

Table 1. Patient’s dose weight adjustment according to BMI:

Note:

• The intermediate calculation of height (m²) should NOT be rounded.
• Dose weight should be rounded to 1 decimal place.

Calculation of patient’s dose volume in millilitres (mL):

Patient’s dose weight in kilograms (kg) × target dose per kilogram (5 × 10¹¹ vg/kg) = dose in vg to be administered

Dose in vg to be administered ÷ Actual concentration (vg/mL)* = patient’s dose volume in mL

^* See the accompanying LIS for information pertaining to the actual concentration of vg per vial.

Special populations

Hepatic impairment

The safety and efficacy of fidanacogene elaparvovec in patients with severe hepatic impairment have not been studied. Fidanacogene elaparvovec is contraindicated in patients with advanced hepatic fibrosis or advanced hepatic cirrhosis (see section 4.3), and not recommended for use in patients with other significant hepatobiliary disorders (see section 4.4).

Patients who are HCV positive/HBV positive/HIV positive

No dose adjustment is needed in patients who are hepatitis C virus (HCV) positive, hepatitis B virus (HBV) positive and/or human immunodeficiency virus (HIV) positive. Limited data are available in patients with controlled HIV infections and a past medical history of active HCV and HBV (see sections 4.3 and 4.4).

Renal impairment

No dose adjustment is needed in patients with renal impairment. The safety and efficacy of BEQVEZ have not been studied in patients with clinically relevant renal impairment (creatinine >2.0 mg/dL).

Elderly

The safety and efficacy of fidanacogene elaparvovec in patients ≥63 years old have not been established. No dose adjustment is needed in elderly patients.

Paediatric population

The safety and efficacy of fidanacogene elaparvovec in children and adolescents under 18 years of age have not yet been established. No data are available.

Method of administration

For intravenous use after dilution.

BEQVEZ is administered as a single-dose intravenous infusion over approximately 60 minutes in an appropriate infusion volume (see section 6.6).

Do not infuse as an intravenous push or bolus. In the event of an infusion reaction during administration, the infusion rate should be slowed or stopped to ensure patient tolerability. If the infusion is stopped, it may be restarted at a slower rate when the infusion reaction is resolved (see section 4.4).

Before administration, it must be confirmed that the patient’s identity matches the unique patient information (i.e., lot number) on the vials, inner cartons, outer cartons, and accompanying documentation. The total number of vials to be administered must also be confirmed with the patient-specific information on the LIS.

For detailed instructions on preparation, administration, measures to take in case of accidental exposure and disposal of medicinal product, see section 6.6.

No data from clinical studies are available regarding overdose of fidanacogene elaparvovec. Close clinical observation and monitoring of laboratory parameters (including clinical chemistry and haematology) for systemic immune response are recommended (see section 4.4). Symptomatic and supportive treatment, as deemed necessary by the treating physician, is advised in the case of overdose.

Unopened frozen vials:

3 years.

Unopened thawed vials:

Frozen vials in the inner carton will take up to 1-hour to thaw at room temperature (up to 30°C). The total time at room temperature between removing vials from frozen storage until the beginning of dose preparation should be no more than 3 hours.

Once thawed, the medicinal product should not be re-frozen and may be stored refrigerated at 2°C to 8°C in the inner carton for 24 hours.

Diluted solution for infusion:

Following dilution in sodium chloride 9 mg/mL (0.9%) solution for injection with 0.25% human serum albumin (HSA), chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 30°C. The administration of fidanacogene elaparvovec dose to the patient should be completed within 24 hours after dose preparation.

Store at −90°C to −60°C and transport at −100°C to −60°C. Original packages removed from frozen storage (−90°C to −60°C) may be kept at room temperature (up to 30°C) for up to 5 minutes for transfer between ultra-low temperature environments.

Store upright in the original package in order to protect from light.

For storage conditions after thawing and dilution of the medicinal product, see section 6.3.

BEQVEZ is supplied in a 2 mL cyclic olefin copolymer vial with an elastomeric stopper and plastic snapfit cap. Each vial contains sufficient volume to ensure 1 mL of extractable volume.

The total number of vials in each finished pack corresponds to the dosing requirement of the individual patient, depending on the body weight and actual concentration, and is provided on the package and LIS. The finished pack will consist of vials, which are included in the inner carton, and placed in the outer carton (patient-specific pack).

Precautions to be taken before handling or administering the medicinal product

BEQVEZ should be transported within the facility in closed, break-proof, and leak-proof containers.

This medicinal product contains genetically modified organisms.

BEQVEZ should be handled aseptically under sterile conditions.

Personal protective equipment (including gloves, safety goggles, laboratory coat and sleeves) should be worn while handling or administering BEQVEZ.

Thawing

• Store in the original package to avoid direct sunlight and ultraviolet light exposure.
• Store BEQVEZ upright in the original package.
• Remove inner carton from the outer carton.
• Thaw BEQVEZ vials in the upright orientation in the inner carton for 1-hour at room temperature (15°C to 30°C).
• Vials may be gently swirled but not shaken or inverted.
• The total time at room temperature between removing vials from frozen storage until the beginning of dose preparation should be no more than 3 hours.
• Visually inspect vials for particulates and discolouration before use. Ensure that visible ice crystals are not present in the solution. Do not use vials that contain visible particulates. The thawed solution in the vial should appear clear to slightly opalescent, colourless to slightly brown solution.
• Vials should not be re-frozen.

Preparation prior to administration

This medicinal product is prepared for intravenous infusion by diluting in sodium chloride 9 mg/mL (0.9%) solution for injection with 0.25% human serum albumin (HSA).

Preparation of diluent solution (sodium chloride 9 mg/mL (0.9%) solution for injection with 0.25% HSA)

• HSA used for preparation of this medicinal product must be commercially available. Either 20% w/v or 25% w/v HSA is recommended.
• Calculate the volume of HSA required to achieve a final concentration of 0.25% w/v HSA in a 200 mL final infusion volume.
• Calculate the volume of medicinal product required for the patient-specific treatment.
  • See the accompanying LIS for information pertaining to the concentration of vector genomes per vial, and for the medicinal product calculation steps.
  • Note: The vector genomes concentration on the LIS is the actual concentration of each vial which should be used for dose preparation calculations.
• Calculate the volume of sodium chloride 9 mg/mL (0.9%) solution for injection required to achieve a final infusion volume of 200 mL when combined with the medicinal product and HSA.
• Combine the calculated volume of HSA with the calculated volume of sodium chloride 9 mg/mL (0.9%) solution for injection in an appropriate intravenous infusion container.
• Mix the diluent solution gently. Do not shake. Incubate the diluent solution in the infusion container at room temperature (15°C to 30°C) for at least 10 minutes prior to adding BEQVEZ.

Preparation of solution for infusion

• Visually inspect thawed product for particulate matter prior to administration. Do not use vials that contain visible particulates.
• Each vial is for single use only.
• Extract the calculated volume of BEQVEZ from the vials using aseptic technique and sterile componentry.
• Combine the extracted volume of BEQVEZ with the diluent solution (0.9% sodium chloride with 0.25% HSA) for a total infusion volume of 200 mL.
• Gently mix the solution for infusion. Do not shake.
• The solution for infusion should be equilibrated to ambient temperature before administration to the patient.

Administration of solution for infusion

• For intravenous use.
• Do not infuse as an intravenous push or bolus.
• An in-line 0.2 μm intravenous filter may be used for administration.
• The solution for infusion should be administered to the patient over approximately 60 minutes.
• In the event of an infusion reaction during administration, the infusion rate should be slowed or stopped (see section 4.4).

Measures to take in case of accidental exposure

Accidental exposure to BEQVEZ must be avoided. In the event of exposure to skin, the affected area must be thoroughly cleaned with soap and water according to local procedures. In the event of exposure to eyes, the affected area must be thoroughly flushed with water for at least 15 minutes.

Precautions to be taken for the disposal of the medicinal product

Unused medicinal product and disposable materials that may have come in contact with BEQVEZ (e.g., vials, all materials used for injection, including needles and any unused product) must be disposed of in compliance with the local guidance for pharmaceutical waste.

All spills of BEQVEZ must be wiped with absorbent gauze pad and the spill area must be disinfected using a bleach solution followed by alcohol wipes. All clean-up materials must be double bagged and disposed of per local guidelines for handling of pharmaceutical waste.