Active Ingredient: Atidarsagene autotemcel
Atidarsagene autotemcel is indicated for the treatment of metachromatic leukodystrophy (MLD) characterized by biallelic mutations in the arylsulfatase A (ARSA) gene leading to a reduction of the ARSA enzymatic activity:
For this indication, competent medicine agencies globally authorize below treatments:
For:
In case that patient age in years is ≤ 7, intravenous, between 3,000,000 cells atidarsagene autotemcel per kilogram of body weight and 30,000,000 cells atidarsagene autotemcel per kilogram of body weight, one dose.
Atidarsagene autotemcel is intended for autologous use and should only be administered once.
The dose of atidarsagene autotemcel must be determined based on the patient’s body weight at the time of infusion.
The minimum recommended dose of atidarsagene autotemcel is 3 × 106 CD34+ cells/kg. In clinical studies, doses up to 30 × 106 CD34+ cells/kg have been administered.
The maximum volume of atidarsagene autotemcel to be administered should remain <20% of the patient’s estimated plasma volume.
The autologous CD34+ cells are isolated from mobilised peripheral blood (mPB). This is achieved by apheresis procedure(s) following peripheral blood mobilisation.
For manufacture of atidarsagene autotemcel, the patient must be able to donate a minimum of 8 × 106 CD34+ cells/kg, considering that the optimal range is between 20-30 × 106 CD34+ cells/kg.
The minimum CD34+ cell quantity may be achieved using one or more cycles of apheresis.
If, after medicinal product manufacturing, the minimum dose of atidarsagene autotemcel of 3 × 106 CD34+ cells/kg is not achieved, the patient may undergo a further mobilisation protocol with one or more cycles of apheresis, in order to obtain more cells for additional manufacture.
A back-up collection of HSPC containing at least 2 × 106 CD34+ cells/kg is also required for use as rescue treatment should the quality of atidarsagene autotemcel be compromised after initiation of myeloablative conditioning and before atidarsagene autotemcel infusion, failure of primary engraftment, or prolonged bone marrow aplasia after treatment with atidarsagene autotemcel.
These cells must be collected from the patient and be cryopreserved according to institutional procedures prior to myeloablative conditioning. The back-up cells may be harvested either through mPB apheresis or bone marrow harvest.
Patients are required to undergo HSPC mobilisation with Granulocyte colony-stimulating factor (G-CSF) with or without plerixafor followed by apheresis to obtain CD34+ stem cells for medicinal product manufacturing.
The treating physician should confirm that autologous HSPC gene therapy administration is clinically appropriate for the patient before myeloablative conditioning is initiated.
A myeloablative conditioning is required before infusion of atidarsagene autotemcel to promote efficient engraftment of the genetically modified autologous CD34+ cells.
Busulfan is the recommended conditioning medicinal product.
Myeloablative conditioning should not begin until the complete set of infusion bag(s) constituting the dose of atidarsagene autotemcel has been received and stored at the qualified treatment centre, and the availability of the back-up collection is confirmed.
Concurrently with the conditioning regimen, and prior to treatment with atidarsagene autotemcel, it is recommended that patients receive prophylaxis for veno-occlusive disease (VOD) and related endothelial injury complications i.e. transplant-associated thrombotic microangiopathy (TA-TMA) or atypical haemolytic uremic syndrome (aHUS), in line with local guidelines.
Depending on the myeloablative conditioning regimen administered, prophylaxis for seizures should also be considered. Phenytoin is not recommended as it may increase busulfan clearance.
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. Routine monitoring of most common viruses subject to re-activation is recommended as per local guidelines. Infection control measures and isolation procedures should be employed during the hospitalization according to local standards.
It is recommended that pre-medication with intravenous chlorpheniramine (0.25 mg/kg, max. dose 10 mg), or equivalent medicinal products, be administered 15-30 minutes before the infusion of atidarsagene autotemcel to reduce the possibility of an infusion reaction.
Administer as an intravenous infusion via a central venous catheter.
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