atidarsagene autotemcel: clinical use

Prescribing considerations

• Confirm biallelic ARSA mutations, reduced enzyme activity, disease subtype and licensed clinical-stage criteria.
• Repeat neurological, motor and age-appropriate neurocognitive assessment before collection and conditioning to exclude rapid progression.
• Use only in a qualified centre with HSCT and gene-therapy expertise; secure suitable back-up stem cells before conditioning.
• Assess organ function, active infection, thyroid status, acid–base status and relevant viral or mycoplasma testing.
• Discuss conditioning-related gonadal toxicity and fertility-preservation options with parents or carers.

Contraindications and cautions

• Hypersensitivity to atidarsagene autotemcel or an excipient.
• Previous haematopoietic stem-cell gene therapy.
• Any contraindication to the required mobilisation or myeloablative medicines.

Monitoring

• Patient identity, product traceability and batch records; retain required traceability information for 30 years after product expiry.
• Vital signs and hypersensitivity during and after infusion, particularly without previous DMSO exposure.
• Blood counts, neutrophil and platelet engraftment, transfusion needs and signs of infection or catheter complications.
• Acid–base status, thyroid function and structure, immunoglobulin G and anti-ARSA antibodies.
• Neurological and developmental course, with long-term surveillance for leukaemia, lymphoma and other delayed effects.
• Avoid PCR-based HIV screening after treatment because the lentiviral vector can cause false-positive nucleic-acid results.

Clinical pharmacology

Autologous CD34-positive haematopoietic stem and progenitor cells are transduced ex vivo with a lentiviral vector carrying human ARSA cDNA. Engrafted cells and their myeloid descendants supply functional ARSA to haematopoietic and nervous-system tissues through cross-correction; conventional pharmacokinetic measures are not applicable.

Formulation and product differences

• The product is a cryopreserved, patient-specific dispersion for intravenous infusion supplied in one or more bags; it is not interchangeable between patients.
• It contains DMSO, sodium chloride and human albumin, must not be mixed with other medicines and must be used promptly after thawing.