Atidarsagene Autotemcel Dosage

Usual Pediatric Dose for:

Leukocytoclastic Vasculitis

Additional dosage information:

Renal Dose Adjustments
Liver Dose Adjustments
Precautions
Dialysis
Other Comments

Usual Pediatric Dose for Leukocytoclastic Vasculitis

Dosing is based on metachromatic leukodystrophy subtype and patient weight at time of infusion:

Pre-symptomatic late infantile (PSLI): 4.2 x 10(6) to 30 x 10(6) CD34+ cells/kg IV once as a single dose
Pre-symptomatic early juvenile (PSEJ): 9 x 10(6) to 30 x 10(6) CD34+ cells/kg IV once as a single dose
Early symptomatic early juvenile (ESEJ): 6.6 x 10(6) to 30 x 10(6) CD34+ cells/kg IV once as a single dose

Comments:

Administer each infusion bag IV within 30 minutes via a central venous catheter; calculate the infusion rate based on the volume in each bag.
Complete infusion within 2 hours of thawing product.
Mobilization, apheresis, and myeloablative conditioning are required prior to administering this drug.
Confirm that hematopoietic stem cell (HSC) gene therapy is appropriate for the patient before starting pre-treatment procedures.
Refer to the manufacturer's Lot Information Sheet for additional information pertaining to the dose.
Safety and efficacy have not yet been established in children with the late juvenile form of MLD.

Use: For the treatment of children with PSLI, PSEJ, or ESEJ metachromatic leukodystrophy

Renal Dose Adjustments

Data not available. This drug has not been studied in pediatric patients with renal dysfunction.

Comments:

Assess children for renal impairment to ensure HSC transplantation is appropriate.

Liver Dose Adjustments

Data not available. This drug has not been studied in pediatric patients with liver dysfunction.

Comments:

Assess children for liver impairment to ensure HSC transplantation is appropriate.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have been established in pediatric patients as young as 8 months of age.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

For one-time, single-dose IV use only.
For autologous use only: Ensure patient identity matches patient identifiers on the drug infusion bag(s).
General advice is provided below; consult the manufacturer product information for detailed instructions on the receipt, preparation, and administration of this drug.

Preparation for treatment:

Screen patients for specified infectious diseases before collecting cells for drug manufacturing.
Obtain CD34+ cells via HSC mobilization followed by apheresis; refer to the manufacturer product information for detailed instructions.
Administer myeloablative conditioning (i.e., busulfan) after this drug has been received and a back-up collection of CD34+ cells has been confirmed.

Infusion of this drug:

Allow a minimum washout period of 24 hours after completion of myeloablative conditioning before infusing this drug.
Intravenously administer the contents of each thawed infusion bag via a central venous catheter within 30 minutes using a gravity or infusion pump; the infusion rate is based on volume of the bag.
Complete the infusion of each bag within 2 hours of thawing the product.
Do NOT use a leukocyte-depleting filter during infusion.
If more than one infusion bag is required to deliver dose, do not administer more than 1 bag per hour.

After treatment:

Irradiate any required blood products within the first 3 months after infusion of this drug.
Patients should not donate blood, organs, tissues, or cells at any time in the future after treatment.

Storage requirements:

Store in the vapor phase of liquid nitrogen at less than -130C (-202F) until ready for thaw and infusion.
Do not refreeze this product after thawing.

Reconstitution/preparation techniques:

Consult the manufacturer product information and the Lot Information Sheet provided with product.
This drug should be thawed and gently mixed before infusion.
Coordinate the timing of thawing and infusion; do not thaw the next infusion bag (if provided) until the previous infusion bag has been fully administered.
Do not shake, sample, alter, or irradiate this product.
Do not wash, spin down, and/or resuspend this drug in new media prior to infusion.

General:

This drug is manufactured for each patient individually and intended for one-time administration to add functional copies of the ARSA gene into the patient's own HSC.
Follow universal precautions and local biosafety guidelines for handling and disposal of this drug to avoid potential transmission of infectious diseases.
Contact the manufacturer of this drug, Orchard Therapeutics, if a blood clot or malignancy is diagnosed.
Review the manufacturer product information for busulfan prior to myeloablative conditioning.

Monitoring:

Cardiovascular: For thrombosis or thrombotic events (after treatment)
Hematologic: For thrombocytopenia and bleeding (until platelet recovery is achieved); absolute neutrophil counts (after infusion)
Hepatic: For liver impairment (prior to therapy to ensure HSC transplantation is appropriate); for signs/symptoms of veno-occlusive disease and assessment of liver function tests (during the first month after infusion)
Hypersensitivity: For signs/symptoms of hypersensitivity reactions (during infusion)
Infectious: For signs/symptoms of serious infection (after conditioning regimen and after drug infusion)
Neurologic: For signs/symptoms of encephalitis (after treatment)
Oncologic: For hematologic malignancies (annually after treatment for at least 15 years)
Renal: For renal impairment (prior to therapy to ensure HSC transplantation is appropriate)

Patient advice:

Understand that due to the risk of manufacturing failure, a collection of unmanipulated CD34+ cells must be collected and cryopreserved; these cells may also be used in the event of neutrophil engraftment failure.
Prior to treatment: Know the risks associated with mobilization and myeloablative conditioning agents, and the potential risk for hypersensitivity reactions that may occur with drug infusion.
After treatment monitor for signs and symptoms of (and seek immediate medical attention for): Blood clots, bleeding, encephalitis/neurological deterioration, infection, and liver problems.
Due to the risk of insertional oncogenesis, recognize that lifelong monitoring is required, including assessment for hematologic malignancies (annually) for at least 15 years after treatment.
Do not donate blood, organs, tissues, or cells at any time in the future.