WASKYRA Dispersion for infusion Ref.[116230] Active ingredients: Etuvetidigene autotemcel

Source: European Medicines Agency (EU)  Revision Year: 2026  Publisher: Fondazione Telethon ETS, Via Varese 16/B, 00185 Rome, Italy

4.1. Therapeutic indications

Waskyra is indicated for the treatment of patients aged 6 months and older with Wiskott-Aldrich Syndrome (WAS) who have a mutation in the WAS gene for whom haematopoietic stem cell (HSC) transplantation is appropriate and no suitable human leukocyte antigen (HLA)-matched related haematopoietic stem cell donor is available.

4.2. Posology and method of administration

Waskyra must be administered in a qualified treatment centre by a physician with experience in haematopoietic stem cell transplantation (HSCT) and trained for administration and management of patients treated with the medicinal product.

Before mobilisation, apheresis and reduced intensity conditioning are initiated, it must be confirmed that haematopoietic stem cell (HSC) transplantation is appropriate for the patient.

Physicians should refer to the SmPCs of medicinal products used for pre-treatment, peripheral blood mobilisation and conditioning to ensure appropriate guidance to the patient.

Posology

Waskyra is intended for autologous use only and should be administered once (see section 4.4).

Treatment consists of a single dose for infusion containing a dispersion of viable CD34+ cells in one or more infusion bags.

The dose of Waskyra to be administered is defined based on the patient's body weight at the time of infusion.

The minimum recommended dose is 7 × 106 CD34+ cells/kg of body weight.

The maximum volume of Waskyra to be administered should remain <20% of the patient's estimated plasma volume (see section 4.4 and section 6.6).

See the accompanying Lot Information Sheet (LIS) for additional information pertaining to dose.

Pre-treatment and conditioning

The treating physician should confirm that autologous HSPC gene therapy administration is clinically appropriate for the patient before rituximab and conditioning is initiated (see section 4.4).

Conditioning should not begin until the complete set of infusion bag(s) constituting the dose of Waskyra has been received and stored at the administration site, and the availability of the back-up collection is confirmed.

Peripheral blood mobilisation and apheresis

The autologous CD34+ cells are isolated from mobilised peripheral blood. This is achieved by apheresis procedure(s) following peripheral blood mobilisation.

To obtain CD34+ cells for medicinal product manufacturing and for autologous back up, patients are required to undergo haematopoietic stem and progenitor cell (HSPC) mobilisation with granulocyte-colony stimulation factor (G-CSF) and plerixafor followed by leukapheresis.

A total HSPC collection target of 40 × 106 CD34+ cells/kg is recommended for medicinal product manufacture. In addition to this, at least 3 × 106 CD34+ cells/kg should be collected as autologous back-up The back-up cells may be harvested either through mobilised peripheral blood apheresis or bone marrow harvest.

Pre-treatment with Rituximab and reduced intensity conditioning regimen

Busulfan and fludarabine are the recommended conditioning medicinal products.

 Days
before the
treatment
infusion
Dosing regimenDose
RituximabDay-22
(+/- 1 day)
The infusion of a single dose of
IV Rituximab, a monoclonal
antibody anti-CD20, is
recommended at Day –22 (+/- 1
day) before the infusion of
Waskyra, with the aim to deplete
B cells pre-treatment.

Infusion rate is in accordance
with the summary of product
characteristics (SmPC)

To reduce the occurrence of
potential adverse reactions,
Rituximab infusion should be
preceded by appropriate
premedication with IV
antihistaminic medicinal product,
paracetamol, and steroids,
following standard procedures.
These should be repeated after 6
hours.
375 mg/m²
BusulfanDay-4 to
Day-2
Patients will receive body
weight-based doses of IV
busulfan.

Patients are scheduled to receive
a total of 8 doses, given every
6 hours from Day-4 to Day-2. If
the target AUC of
48 000 ng/mL*h (± 10%) is not
achieved with 8 doses, additional
doses may be administered.
Dosing will be stopped if the
target AUC was reached prior to
the eighth dose.

Dose adjustment will be
performed according to busulfan
PK levels to achieve the target
cumulative AUC of
48 000 ng/mL*h (± 10%).

The Waskyra cell infusion will
be scheduled to allow a washout
time of at least 24 hours from the
last dose of busulfan.
The starting dose of busulfan is
based on patient's weight
according to the following
scheme:

• 1 mg/kg/dose (<9 kg);
• 1.2 mg/kg/dose (9 - 16 kg);
• 1.1 mg/kg/dose (>16 - 23 kg);
• 0.95 mg/kg/dose (>23 - 34 kg);
• 0.8 mg/kg/dose (>34 kg).

The subsequent doses of
busulfan should be estimated
from pharmacokinetics (PK)
sampling and adjusted
accordingly. The busulfan PK
analysis should be performed by
serial blood sampling before and
after the infusion of at least two
separate doses usually the first
and fifth dose.

Special attention should be kept
on the busulfan dosing in order
to achieve the target cumulative
AUC of 48 000 ng/ml*h (± 10%).
A dose adjustment should be
performed if the total predicted
AUC shows more than 10%
deviation from the target
(total predicted
AUC is <43 200 ng/mL*h or
>52 800 ng/mL*h).

The number of doses of Busulfan
may be decreased if the
cumulative predicted AUC is too
high.
FludarabineDay-4 and
Day-3
Fludarabine is administered IV
once daily in Day-4 and Day-3.

The infusion rate should be in
accordance with the fludarabine
Summary of Product
Characteristics (SmPC).
30 mg/m²/day

AUC = area under the curve; IV=intravenous; PK=pharmacokinetic; m² = square meter

Prevention and management of infections during pre-treatment

Prophylactic and empiric use of anti-infectives (bacterial, fungal, viral) should be considered for the prevention and management of infections especially during the neutropenic period following conditioning (see section 4.4). Infection control measures and isolation procedures should be employed during the hospitalisation according to local standards.

Premedication

Antiallergic medicinal products, such as intravenous chlorpheniramine, are recommended be administered 15-30 minutes before the infusion of Waskyra to reduce the possibility of an allergic reaction to the infusion.

Special populations

Elderly

Waskyra has not been studied in patients >65 years of age.

Patients seropositive for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)

Waskyra has not been studied in patients with HIV-1, HIV-2, active HBV, or active HCV. Patients should be screened for HIV-1, HIV-2, HBV, and HCV and any other infectious agents in accordance with local guidelines before collection of cells for manufacturing.

Patients with serious haematological disorders

Waskyra has not been studied in patients with evidence of myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukemia, or other serious hematological disorders. Treatment with Waskyra is not recommended in these patients.

Paediatric population

The safety and efficacy of Waskyra in patients < 6 months of age have not yet been established. No data are available.

Method of administration

Waskyra is for intravenous infusion only.

Prior to Waskyra infusion, it must be confirmed that the patient's identity matches the essential unique patient information on the Waskyra infusion bag(s) labels and accompanying documentation. When more than one bag of Waskyra is needed, only one bag of medicinal product should be infused at a time. The total number of infusion bags to be administered must also be confirmed with the patient specific information on the Lot Information Sheet (LIS) (see section 4.4).

Waskyra infusion will be scheduled to allow a washout time of at least 24 hours from the last dose of busulfan.

The timing of thaw and infusion of Waskyra should be coordinated. The infusion start time should be confirmed in advance and adjusted for thaw so that Waskyra is available for infusion when the patient is ready. To maintain product viability, as soon as thawing is complete, it is recommended that Waskyra is administered immediately. Administration must be completed within 2 hours from the time of thawing.

Administration

Administer the product as an intravenous infusion via a central venous catheter. When more than one bag of Waskyra is provided, one bag of medicinal product should be thawed at a time.

Each bag should be infused at an infusion rate which does not exceed 5 mL/kg/h, within approximately 30 minutes. The recommended administration set consists of a blood transfusion set equipped with a 200 μm filter.

Patients should be monitored closely prior to, during, and after infusion. Vital signs (blood pressure, heart rate, and oxygen saturation) and the occurrence of any symptom should be checked every ten minutes during the infusion and every hour, for 3 hours, after the infusion (see section 4.4).

Patients should be monitored frequently by complete blood count for at least 6 weeks after infusion or until recovery of haematopoiesis and infections managed according to standard guidelines and medical judgement (see section 4.4).

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

4.9. Overdose

No data from clinical trials are available regarding overdose of Waskyra.

6.3. Shelf life

6 months.

Once thawed, maximum 2 hours at room temperature (20°C - 25°C). For products formulated at 2 × 106 cells/mL, the maximum time at room temperature should be 45 minutes.

6.4. Special precautions for storage

Waskyra infusion bags must be stored in the vapour phase of liquid nitrogen (< -130°C) and must remain frozen until the patient is ready for treatment to ensure viable cells are administered to the patient.

Keep the infusion bag(s) in the metal cassette(s). Do not unseal the overwrap bag before thawing. Do not re-freeze after thawing.

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

6.5. Nature and contents of container

50 mL ethylene vinyl acetate (EVA) infusion bag(s) with two available spike ports, packed in an EVA overwrap bag placed inside a metal cassette.

Waskyra is shipped from the manufacturing facility to the treatment centre storage facility in a cryoshipper, which may contain multiple metal cassettes intended for a single patient.

Each metal cassette contains one infusion bag of Waskyra.

6.6. Special precautions for disposal and other handling

Precautions to be taken before handling or administering the medicinal product:

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

  • This medicinal product contains genetically modified human blood cells. Healthcare professionals handling Waskyra should take appropriate precautions (wearing gloves, protective clothing and eye protection) to avoid potential transmission of infectious diseases.
  • Waskyra must remain at < -130°C at all times, until the content of the bag is thawed for infusion.

Definition of the dose to be administered:

  • Careful consideration must be given to the volume of infusion in relation to age and weight of the patient. When the dose of Waskyra to be infused represents more than one bag, it should be ensured prior to infusion that the volume of medicinal product 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. Therefore, the maximum volume of Waskyra to be administered should remain <20% of the patient's estimated plasma volume (see section 4.4).

Preparation for the infusion:

  • A patient may have multiple infusion bags. Each infusion bag is provided inside an overwrap bag, which is contained in a metal cassette.
  • The overwrapped infusion bag(s) must be kept inside the metal cassette(s) in the vapour phase of liquid nitrogen at < -130°C until ready to thaw and infuse.
  • Account for all infusion bags and confirm each infusion bag is within the expiry date.

Checking prior to thawing:

  • Do not remove the metal cassette from cryogenic storage or thaw Waskyra until the patient is ready to be infused. The timing of thaw of the infusion bag(s) containing Waskyra and of the infusion should be coordinated. 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.
  • 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. The total number of infusion bags to be administered must also be confirmed with the patient specific information on the Lot Information Sheet (LIS).

Thawing:

  • After careful removal from the metal cassette, thaw the infusion bag in its sealed overwrap bag at 37°C in a controlled thawing device until there is no visible ice in the infusion bag.
  • Once thawing is complete, the bag should be removed immediately from the thawing device. To maintain product viability, as soon as thawing is complete, it is recommended that Waskyra is administered immediately. Administration must be completed within 2 hours from the time of thawing.
  • 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.
  • The infusion bag should not be washed, spun down, sampled and/or resuspended in new media prior to infusion.
  • Waskyra should not be irradiated as irradiation could lead to inactivation of the product.
  • If more than one infusion bag is provided for the patient treatment dose, the next bag should only be thawed after the content of the preceding bag has been fully infused.

Administration:

  • Waskyra should be administered as an intravenous infusion via a central venous catheter, per the administration site's standard procedures for cell therapy products.
  • The recommended administration set consists of a blood transfusion set equipped with a 200 μm filter.
  • Each bag should be infused by gravity within 2 hours of thaw, including any interruption during the infusion, to maintain maximum product viability.
  • The maximum infusion rate is 5 mL/kg/h, and the content of each bag should be infused within approximately 30 minutes.
  • When more than one bag of Waskyra is needed, one bag of medicinal product should be thawed at a time.
  • Patients not previously exposed to DMSO should be observed closely. Vital signs (blood pressure, heart rate, and oxygen saturation) and the occurrence of any symptom should be monitored for up to 3 hours following the infusion.
  • 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. Careful consideration must be given to the volume of infusion in relation to the age and weight of the patient.

Precautions to be taken for the disposal of the medicinal product:

  • Unused medicinal products and all material that has been in contact with Waskyra (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling human-derived material.

Accidental exposure:

  • In case of accidental exposure, local guidelines on handling of human-derived material should be followed. Work surfaces and materials which have potentially been in contact with Waskyra must be decontaminated with appropriate disinfectant.

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