SKYSONA Dispersion for infusion Ref.[49634] Active ingredients: Elivaldogene autotemcel

Skysona must be administered in a qualified treatment centre by a physician(s) with experience in HSC transplantation and in the treatment of patients with neurological disorders.

Posology

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

The minimum recommended dose of Skysona is 5 × 10⁶ CD34+ cells/kg. In clinical studies doses up to 38.2 × 10⁶ CD34+ cells/kg have been administered.

Mobilisation and apheresis

Patients are required to undergo HSC mobilisation followed by apheresis to obtain CD34+ stem cells which will be used for medicinal product manufacturing (see section 5.1 for description of the mobilisation regimen used in clinical studies).

The patient’s weight at first apheresis collection should be used to calculate the final dose.

The minimum target number of CD34+ cells to be collected is 12 × 10⁶ CD34+ cells/kg. If the minimum dose of Skysona 5 × 10⁶ CD34+ cells/kg is not met after initial medicinal product manufacturing, the patient may undergo one or more additional cycles of mobilisation and apheresis, separated by at least 14 days, in order to obtain more cells for additional manufacture.

A back-up collection of CD34+ stem cells of ≥1.5 × 10⁶ CD34+ cells/kg is required. These cells must be collected from the patient and be cryopreserved prior to initiating conditioning and infusion with Skysona. The back-up collection may be needed for rescue treatment if there is: 1) compromise of Skysona after initiation of conditioning and before Skysona infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with Skysona (see section 4.4).

Pre-treatment conditioning

The treating physician should confirm that Skysona therapy is appropriate for the patient before conditioning is initiated (see section 4.4).

Myeloablative conditioning must be administered before infusion of Skysona (see section 5.1 for a description of the conditioning regimens used in clinical studies).

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

Skysona administration

See Method of Administration below and section 6.6 for details on Skysona administration and handling.

After Skysona administration

Any blood products required within the first 3 months after Skysona infusion should be irradiated.

Special populations

Previous gene therapy administration

Skysona has not been studied in patients previously treated with a gene therapy medicinal product. There is no experience treating a patient more than once with Skysona.

Renal impairment

Skysona has not been studied in patients with renal impairment. Patients should be assessed for renal impairment to ensure Skysona therapy is appropriate. No dose adjustment is required.

Hepatic impairment

Skysona has not been studied in patients with hepatic impairment. Patients should be assessed for hepatic impairment to ensure Skysona therapy is appropriate. No dose adjustment is required.

Female patients

The safety and efficacy of Skysona in female patients have not been established. No data are available.

Paediatric population

The safety and efficacy of Skysona in children aged up to 3 years have not been established. No data are available.

Patients seropositive for human immunodeficiency virus (HIV)

Skysona has not been studied in patients with HIV-1, HIV-2, HTLV-1, and HTLV-2. A negative serology test for HIV is necessary to ensure acceptance of apheresis material for Skysona manufacturing. Apheresis material from patients with a positive test for HIV will not be accepted for Skysona manufacturing.

Method of administration

Skysona is for intravenous use only.

For detailed instructions on preparation, administration, accidental exposure and disposal of Skysona, see section 6.6.

After completion of the conditioning, there must be a minimum of 48 hours of washout before Skysona infusion.

Before infusion, it must be confirmed that the patient’s identity matches the unique patient information on the Skysona infusion bag(s). The total number of infusion bags to be administered should also be confirmed with the Lot Information Sheet (see section 4.4).

Skysona infusion should be completed as soon as possible and no more than 4 hours after thawing. Each infusion bag should be administered in less than 60 minutes. In the event that more than one infusion bag is provided, all infusion bags must be administered consecutively. The entire volume of each infusion bag should be infused.

Standard procedures for patient management in line with HSC transplantation should be followed after Skysona infusion.

No data from clinical studies are available regarding overdose of Skysona.

6 months.

Once thawed: maximum 4 hours at room temperature (20ºC–25ºC).

Store in the vapour phase of liquid nitrogen at ≤ -140°C until ready for thaw and administration.

Keep infusion bag(s) in the metal cassette(s).

Do not re-freeze after thawing.

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

Approximately 20 mL in a fluoro ethylenepropylene infusion bag(s), each packed in a transparent pouch inside a metal cassette.

Skysona is shipped from the manufacturing facility to the infusion centre storage facility in a cryoshipper, which may contain multiple metal cassettes intended for a single patient. Each metal cassette contains one infusion bag with Skysona. One lot of drug product may be packaged in either one or two 20 mL bags, depending on the total number of cells present. Multiple lots may be administered to the patient as a single dose.

Irradiation could lead to inactivation of the product.

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

• This medicinal product contains genetically modified human blood cells. Healthcare professionals handling Skysona should take appropriate precautions (wearing gloves, protective clothing and eye protection) to avoid potential transmission of infectious diseases.
• Keep the infusion bag(s) in the metal cassette(s) and store in the vapor phase of liquid nitrogen at ≤ -140°C until ready for thaw and administration.

Preparation for the infusion:

• Remove each metal cassette from liquid nitrogen storage and remove each infusion bag from the metal cassette.
• Confirm that Skysona is printed on the infusion bag(s).
• Confirm that patient identity matches the unique patient identification information located on the Skysona infusion bag(s) and on the Lot Information Sheet. Skysona is intended solely for autologous use. Do not infuse Skysona if the information on the patient-specific label on the infusion bag does not match the intended patient.
• Ensure that you have the correct number of infusion bags and confirm each infusion bag is within the expiry date using the accompanying Lot Information Sheet.
• Each infusion bag should be inspected for any breaches of integrity before thawing and infusion. If an infusion bag is compromised, follow the local guidelines for handling of waste of humanderived material and contact bluebird bio immediately.

Thawing:

• If more than one infusion bag is provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag.
• Do not sample, alter, irradiate, or refreeze the medicinal product.
• Thaw Skysona at 37°C in a water bath or dry bath. Thawing of each infusion bag takes approximately 2 to 4 minutes. Do not over thaw the medicinal product. Do not leave the medicinal product unattended and do not submerge the infusion ports in a water bath.
• After thaw, mix the medicinal product gently by massaging the infusion bag until all of the contents are uniform.

Administration:

• Expose the sterile port on the infusion bag by tearing off the protective wrap covering the port.
• Access the medicinal product infusion bag and infuse per the administration site’s standard procedures for administration of cell therapy products. Do not use an in-line blood filter or an infusion pump.
• Infuse Skysona as soon as possible and store for no more than 4 hours at room temperature (20ºC–25ºC) after thawing.
• Administer each infusion bag of Skysona via intravenous infusion over a period of less than 60 minutes.
• Flush all Skysona remaining in the infusion bag and any associated tubing with at least 50 mL of sodium chloride 9 mg/mL (0.9%) solution for injection to ensure as many cells as possible are infused into the patient.

Precautions to be taken for the disposal of the medicinal product

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

Accidental exposure

In case of accidental exposure, local guidelines on handling of human derived materials should be followed, which may include washing of the contaminated skin and removal of contaminated clothes. Work surfaces and materials which have potentially been in contact with Skysona must be decontaminated with appropriate disinfectant.