WASKYRA Suspension for solution for infusion Ref.[116110] Active ingredients: Etuvetidigene autotemcel

For autologous use only. For single-dose intravenous use only.

2.1 Recommended Dose

The minimum recommended dose of WASKYRA is 7 × 10⁶ CD34+ cells/kg based on patient's body weight at the time of infusion.

The maximum volume of WASKYRA to be administered should remain <20% of the patient's estimated plasma volume.

2.2 Patient Preparation before WASKYRA Infusion

Mobilisation and apheresis:

• Mobilize hematopoietic stem and progenitor cells (HSPC) using G-CSF with plerixafor according to established protocols.
• Perform apheresis to collect CD34+ cells required for WASKYRA manufacturing following the mobilization procedure.
• Collect and cryopreserve a back-up supply of CD34+ stem cells containing at least 3 x 10⁶ CD34+ cells/kg from the patient. Complete this collection before initiating reduced intensity conditioning and WASKYRA infusion.
• Store the back-up collection for potential rescue treatment in the following scenarios: WASKYRA compromise after reduced intensity conditioning initiation but before scheduled infusion, primary engraftment failure, or prolonged bone marrow aplasia following WASKYRA treatment.

Pre-treatment and conditioning:

• Administer rituximab (anti-CD20 monoclonal antibody) approximately 22 days before WASKYRA administration to deplete autoreactive B-cells and provide pre-emptive treatment for potential lymphoproliferative disorder due to Epstein Barr Virus infection which is a risk factor in WAS patients.
• Administer busulfan and fludarabine for reduced intensity conditioning before infusion of WASKYRA to promote engraftment of the genetically modified autologous CD34+ cells.
• Do not begin conditioning until the complete set of infusion bag(s) constituting the dose of WASKYRA has been received and stored at the administration site. Confirm availability of the back-up collection.

Premedication:

Administer intravenous chlorpheniramine (0.2 mg/kg, max. dose 10 mg), or an equivalent 15-30 minutes before the infusion of WASKYRA to reduce the possibility of an allergic reaction to the infusion.

2.3 Administration

Receipt:

WASKYRA is shipped in the vapor phase of liquid nitrogen (<-130°C) from the manufacturing site to the qualified treatment center for the infusion. The Lot Information Sheet and the Chain of Custody documentation travels with the cryoshipper.

Upon arrival check the temperature on the display of the cryoshipper, open it using the proper DPI, and confirm the patient code, batch number and number of bags against product label(s).

Transfer WASKYRA from the vapor phase of liquid nitrogen at less than -130°C (-202°F) to the treatment center vapor phase of liquic nitrogen storage (<-130°C) until ready for thaw and administration.

In the event of issues, contact Fondazione Telethon ETS at: 1-888-212-6928.

Preparation for infusion:

WASKYRA contains human blood cells that are genetically modified with a replication-incompetent, self-inactivating lentiviral vector (LVV). Follow universal precautions and local biosafety guidelines for handling and disposal of WASKYRA to avoid potential transmission of infectious diseases.

Checking prior to thawing:

• Do not remove the metal cassette from cryogenic storage or thaw WASKYRA until the patient is ready to be infused. Coordinate the timing of WASKYRA thaw and infusion. Confirm the infusion time in advance and adjust the start time for thaw so that the treatment is available for infusion when the patient is ready.
• Ensure the correct number of infusion bags are present. When more than one bag of WASKYRA is provided, thaw one bag of WASKYRA at a time. If more than one infusion bag is provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag.
• Open the metal cassette and inspect the overwrap bag and infusion bag for any breaches of integrity before thawing. If an infusion bag is compromised, follow the local guidelines for handling of waste of human-derived material and contact Marketing Authorization Holder immediately.
• Prior to thawing WASKYRA, it must be verified that the patient identity matches the unique patient information reported on the packaging labels and Lot Information Sheet (LIS). WASKYRA is solely for autologous use. Do not thaw or infuse WASKYRA if the information on the patient-specific label on the infusion bag does not match the intended patient.
• Confirm that the infusion bag is within the expiration date.

Thawing:

1. After carefully removing from the metal cassette, thaw the infusion bag in its sealed overwrap bag at 37°C (98.6°F) in a controlled thawing device until there is no visible ice in the infusion bag.

2. Once thawing is complete, the bag should be removed immediately from the thawing device.

3. The overwrap bag should be carefully opened to remove the infusion bag which should be kept at room temperature (20°C – 25°C) until infusion. Gently massage the infusion bag to resuspend the cells. The content of the infusion bag should be inspected for any remaining visible cellular aggregates. Small clumps of cellular material should disperse with gentle manual mixing. Do not shake the bag.

4. To maintain product viability, as soon as possible after thawing is complete, it is recommended that WASKYRA is administered immediately.

Note: Do not sample, alter, irradiate or refreeze WASKYRA.

Administration:

Prior to WASKYRA infusion, confirm that the patient's identity matches the essential unique patient information on the infusion bag(s) labels.

Administer WASKYRA as an intravenous infusion using a central venous catheter, per the qualified treatment site's standard procedures for cell therapy products.

When more than one bag of WASKYRA is needed, prior to infusion ensure that the volume of WASKYRA to be infused is compatible with the recommended limit of DMSO, i.e., the total volume of DMSO administered should remain <1% of the patient's estimated plasma volume. The maximum volume of WASKYRA to be administered should therefore remain <20% of the patient's estimated plasma volume.

1. Ensure that the administration set consists of a blood transfusion set equipped with a 200 μm filter.

2. Infuse each bag by gravity within 2 hours of thaw, including any interruption during the infusion, to maintain maximum product viability.

3. Infuse contents of each bag within 30 minutes with a maximum infusion rate of 5 mL/kg/h.

4. At the end of the infusion, flush all WASKYRA remaining in the infusion bag and any associated tubing with sodium chloride 9 mg/mL (0.9%) solution for injection to ensure that as many cells as possible are infused into the patient. Consider the infusion volume in relation to the age and weight of the patient.

Monitor vital signs (blood pressure, heart rate, and oxygen saturation) and the occurrence of any symptom prior to the start of the infusion, approximately every ten minutes during the infusion and every hour, for 3 hours, after the infusion.

• 50 mL infusion bag, overwrap, and metal cassette (NDC XXXXX-XXXX-X).
• Match the identity of the patient with the patient identifiers, and Lot Information Sheet upon receipt.
• Store WASKYRA in the vapor phase of liquid nitrogen at less than -130°C (-202°F) until ready for thaw and administration.
• Thaw WASKYRA prior to infusion [see Dosage and Administration (2)].
• Do not re-freeze after thawing.
• Do not irradiate WASKYRA, as this could lead to inactivation.