Upstaza

/ Medison

Patients will receive a total dose of 1.8 × 10^11 vg delivered as four 0.08 mL (0.45 × 10^11 vg) infusions (two per putamen).
The posology is the same for the entire population covered by the indication.

Clinical, molecular, and genetically confirmed diagnosis of aromatic L-amino acid decarboxylase (AADC) deficiency with a severe phenotype, in patients aged 18 months and older.

Hypersensitivity to the active substance(s) or to any of the excipients

Monitoring
Patients undergoing gene therapy should be closely monitored for procedure-related complications, complications related to their underlying disease, and risks associated with general anaesthesia during the peri-operative period. Patients may experience exacerbations of symptoms of their underlying AADC deficiency as a result of surgery and anaesthesia. Autonomic and serotonergic symptoms of AADC may persist after treatment with eladocagene exuparvovec.
Cerebrospinal fluid leaks
Cerebrospinal fluid (CSF) leaks occur when there is a tear or hole in the meninges surrounding the brain or spinal cord, allowing the CSF to escape. Upstaza is administered by bilateral intraputaminal infusion using burr holes, therefore, CSF leak may occur postoperatively. Patients undergoing eladocagene exuparvovec treatment should be carefully monitored after administration for CSF leaks, particularly in relation to the risk of meningitis and encephalitis.
Dyskinesia
AADC-deficient patients may have increased sensitivity to dopamine due to their chronic dopamine deficiency. Dyskinesia has been reported in 26/30 patients after treatment with eladocagene exuparvovec. The occurrence of dyskinesia is due to dopamine sensitivity and generally starts 1 month after the administration of gene therapy and gradually decreases over several months. Events of dyskinesia were managed with routine medical care, such as antidopaminergic treatment (eg, risperidone).
Risk of viral shedding
The risk of shedding is considered to be low due to very limited systemic distribution of eladocagene exuparvovec. As a precautionary measure, patients/caregivers should be advised to handle waste material generated from dressings and/or any secretions (tears, blood, nasal secretions, and CSF) appropriately, which may include storage of waste material in sealed bags prior to disposal and patients/caregivers wearing gloves for dressing changes and waste disposal, especially in case of pregnancy, breast-feeding, or immunodeficiency of caregivers. These handling precautions should be followed for 14 days after administration of eladocagene exuparvovec.
Blood, organ, tissue, and cell donation
Patients treated with Upstaza must not donate blood, organs, tissues, and cells for transplantation.
See prescribing information for full details.

Very common: Initial insomnia, Dyskinesia, Anaemia, Cerebrospinal fluid leakage, Pneumonia, Hypokalaemia, Irritability, Hypotension, Upper gastrointestinal haemorrhage, Diarrhoea, Decubitus ulcer, Pyrexia, Breath sounds abnormal.
Common: Feeding disorders, Irritability, Salivary hypersecretion, Gastroenteritis, Dyskinesia, Cyanosis, Hypovolemic shock, Respiratory failure, Mouth ulceration, Dermatitis diaper, Rash, Hypothermia, Tooth extraction.
See prescribing information for full details.

No interaction studies have been performed. No interaction is expected due to very limited systemic distribution of eladocagene exuparvovec.
See prescribing information for full details.

Based on the lack of systemic exposure and negligible biodistribution to the gonads, the risk for germline transmission is low.
Pregnancy: There are no data from the use of eladocagene exuparvovec in pregnant women
Lactation: It is unknown whether eladocagene exuparvovec is excreted in human milk. Eladocagene exuparvovec is not absorbed systemically following intraputaminal administration, and no effect on the breastfed newborns/infants are anticipated.
See prescribing information for full details.

There is no clinical experience with overdose of eladocagene exuparvovec. Symptomatic and supportive treatment, as deemed necessary by the treating physician, is advised in case of overdose. Close clinical observation and monitoring of laboratory parameters (including complete blood count with differential, and comprehensive metabolic panel) for systemic immune response are recommended.

Store and transport frozen at ≤ -65° C