Lenmeldy Dosage

Dose

LENMELDY is provided as a single dose for infusion containing a suspension of CD34 +cells in one to eight infusion bags. Table 1 provides the minimum and maximum recommended dose of LENMELDY based on MLD disease subtype:

The dose administered is calculated based on the child’s weight at time of LENMELDY infusion using the information provided on the Lot Information Sheet. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose.

Preparation before LENMELDY Infusion

Mobilization, apheresis, and myeloablative conditioning are required prior to LENMELDY infusion. Before initiating these procedures, confirm that hematopoietic stem cell (HSC) gene therapy is appropriate for the child.

Screen children for hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotrophic virus 1 & 2 (HTLV-1/HTLV-2), human immunodeficiency virus 1 & 2 (HIV-1/HIV-2), cytomegalovirus (CMV), and mycoplasma infection in accordance with clinical guidelines before collection of cells for manufacturing.

Mobilization and Apheresis

Children are required to undergo HSC mobilization followed by apheresis to obtain CD34 +cells for LENMELDY manufacturing. In clinical trials of LENMELDY, granulocyte-colony stimulating factor (G-CSF) with or without plerixafor was used for mobilization.

For the manufacture of LENMELDY, a collection of a minimum of 8.0 × 10 6CD34 +cells/kg of autologous cells is required based on a weight at time of apheresis collection. Collection of the minimum number of CD34 +cells required for manufacture may be achieved using one or more cycles of mobilization.

A collection of unmanipulated back-up CD34 +cells of at least 2.0 × 10 6CD34 +cells/kg is required. These cells must be collected from the child and be cryopreserved prior to myeloablative conditioning. The back-up collection may be needed for rescue treatment if there is: 1) compromise of LENMELDY after initiation of conditioning but before infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with LENMELDY. The back-up cells may be collected either through mobilized peripheral blood (mPB) apheresis or bone marrow collection.

Myeloablative Conditioning

Myeloablative conditioning must be administered before infusion of LENMELDY. In clinical trials of LENMELDY, busulfan was used for myeloablative conditioning. There is no data available supporting the use of alternative conditioning agents with LENMELDY.

Do not begin myeloablative conditioning until LENMELDY has been received and stored at the treatment center and the availability of the back-up collection of CD34 +cells has also been confirmed. After completion of the myeloablative conditioning, allow a minimum of 24 hours of washout before LENMELDY infusion.

Receipt and Storage of LENMELDY

• LENMELDY is shipped to the treatment center in the vapor phase of liquid nitrogen at less than -130°C (-202°F) along with the corresponding Lot Information Sheet. Two shippers would be used in the event that 5-8 bags are manufactured.
  
  
• Confirm patient identifiers on the product labels and the Lot Information Sheet.
  
  
• If there are any concerns about the product or packaging upon receipt, contact Orchard Therapeutics at 1-888-878-0185.
  
  
• Keep the infusion bag(s) in the metal cassette(s) and transfer LENMELDY from the transport vapor phase of liquid nitrogen shipper to the treatment center’s own vapor phase of liquid nitrogen storage at less than -130°C (-202°F). Store in the vapor phase of liquid nitrogen at less than -130°C (-202°F) until ready for thaw and administration.
  

Preparation of LENMELDY for Infusion

Coordinate the timing of LENMELDY thaw and infusion. Confirm the infusion time in advance and adjust the start time of LENMELDY thaw such that it will be available for infusion when the child and healthcare providers are ready to initiate LENMELDY administration as soon as possible after thaw. Each bag of LENMELDY should be infused via a central venous catheter and must be infused within 2 hours, post-thawing.

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

Ensure the correct number of infusion bags are present. Use the corresponding Lot Information Sheet to confirm the number of LENMELDY bags shipped to the treatment center. A maximum of eight bags may be provided per child, which would take a maximum of approximately 16 hours to complete the infusion process. If more than one infusion bag is provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag. The following steps must be repeated for each LENMELDY infusion bag immediately prior to thaw.

1. Remove the metal cassette from the vapor phase of liquid nitrogen storage.
   
   
2. Confirm that "LENMELDY" is printed on the infusion bag label.
   
   
3. Confirm that the child's identity matches the unique patient identifiers located on the LENMELDY infusion bag. Do not infuse LENMELDY if the information on the patient-specific label on the infusion bag does not match the intended patient, and contact Orchard Therapeutics at 1-888-878-0185.
   
   
4. Use the accompanying Lot Information Sheet to confirm that the infusion bag is within the expiration date.
   
   
5. Inspect the infusion bag for any breaches of integrity before thawing and infusion. If an infusion bag is compromised, follow the local guidelines and contact Orchard Therapeutics immediately at 1-888-878-0185.
   
   
6. Thaw LENMELDY in the overwrap bag at 37°C (98.6°F) in a controlled thawing device. Once thawing is complete, the bag should be removed immediately from the thawing device. The overwrap bag should be carefully opened to remove the infusion bag which should be kept at room temperature until infusion.
   
   
7. After thawing, mix the contents gently by massaging the infusion bag to homogenize the cell suspension and disperse any remaining cell aggregates. If visible cell aggregates remain, continue to gently mix the contents of the bag. Most cell aggregates should disperse with gentle manual mixing. Do not shake the bag. Do not wash, spin down and/or resuspend LENMELDY in new media prior to infusion.
   

• Do not sample, alter, irradiate, or refreeze LENMELDY.
  

Administration

LENMELDY is for autologous use only. The child’s identity must match the patient identifiers on the LENMELDY cassette(s) and infusion bag(s). Do not infuse LENMELDY if the information on the patient-specific label does not match the intended patient. LENMELDY must not be irradiated or infused using a leukodepleting filter.

1. Before infusion, confirm that the child’s identity matches the unique patient identifiers on the LENMELDY infusion bag.Use the Lot Information Sheet to confirm the total number of infusion bags to be administered.
   
   
2. Prime the tubing of the infusion set with 0.9% sodium chloride solution prior to infusion.
   
   
3. Expose the sterile port on the infusion bag by tearing off the protective wrap covering the port.
   
   
4. Access the infusion bag and infuse LENMELDY as soon as possible after thawing and complete the infusion within 2 hours after thawing.
   
   
5. Administer each infusion bag of LENMELDY as an intravenous infusion via a central venous catheter within 30 minutes via gravity or infusion pump. An infusion flow rate should be calculated based on the volume in each infusion bag.
   
   
6. After the entire content of the infusion bag is infused, flush all LENMELDY remaining in the infusion bag and any associated tubing with 0.9% sodium chloride solution using a rinse volume that is equal to or greater than the priming volume of any intravenous infusion set used to ensure that as many cells as possible are infused into the child.
   
   
7. If more than one infusion bag is provided, administer the content of each infusion bag completely before proceeding to thaw (following Section 2.2steps 1-7) and infuse (following Section 2.3steps 1-6) the content of the next infusion bag. If more than one infusion bag is necessary, do not administer more than one bag of product per hour.
   

After LENMELDY Administration

Standard procedures for patient management after HSC transplantation should be followed after LENMELDY infusion.

• Irradiate any blood products required within the first 3 months after LENMELDY infusion.
  
  
• Children treated with LENMELDY should not donate blood, organs, tissues, or cells at any time in the future.