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Upstaza is a brand name for Eladocagene Exuparvovec. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Upstaza is indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L-amino acid decarboxylase (AADC) deficiency with a severe phenotype (see section 5.1).
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should be administered in a centre which is specialised in stereotactic neurosurgery, by a qualified neurosurgeon under controlled aseptic conditions. 45 × 1011 vg) infusions (two per putamen). The posology is the same for the entire population covered by the indication.
3 Special populations Paediatric population The safety and efficacy of eladocagene exuparvovec in children aged below 18 months have not yet been established. No data are available. There is limited experience in patients aged 12 years and older.
The safety and efficacy of eladocagene exuparvovec in these patients have not been established. 1. No dose adjustment should be considered. Hepatic and renal impairment The safety and efficacy of eladocagene exuparvovec in patients with hepatic and renal impairment have not been evaluated.
4). Method of administration Intraputaminal use. Preparation Upstaza is a sterile solution for infusion that requires thawing and preparation by the hospital pharmacy prior to administration. 6. Neurosurgical administration Upstaza is a single use vial administered by bilateral intraputaminal infusion in one surgical session at two sites per putamen.
Four separate infusions of equal volumes are performed to the right anterior putamen, right posterior putamen, left anterior putamen, and left posterior putamen. 6. The target infusion sites are defined per standard stereotactic neurosurgical practice.
Upstaza is administered as a bilateral infusion (2 infusions per putamen) with an intracranial cannula. The final 4 targets for each trajectory should be defined as 2 mm dorsal to (above) the anterior and posterior target points in the mid-horizonal plane (Figure 1).
Figure 1 Four target points for infusion sites • After stereotactic registration is complete, the entry point on the skull should be marked. Surgical access through the skull bone and dura should be performed. 4 • The infusion cannula is placed at the designation point in the putamen using stereotactic tools based on the trajectories planned.
Of note, the infusion cannula is placed and infusion performed separately for each putamen. 8 × 1011 vg). 08 mL of Upstaza across the planned trajectory to optimise distribution across the putamen. • After the first infusion, the cannula is withdrawn and then re-inserted at the next target point, repeating the same procedure for the other 3 target points (anterior and posterior of each putamen).
5 years at the time of dosing. 7 years). Twenty-six patients treated in the clinical studies enrolled in a long-term follow-up study. 5 years). 7%) patients and was prevalent during the first 2 months post-treatment. Tabulated list of adverse reactions The adverse reactions are reported in Table 1.
The adverse reactions are listed by system organ class and frequency using the following convention: very common (≥ 1/10), common ≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
4). Of the 37 events of dyskinesia, 35 events were mild to moderate and 2 were severe. The majority of events resolved in approximately 2 months, and all resolved within 7 months from symptom onset. The mean time to onset of events of dyskinesia was 25 days after receiving gene therapy.
Events of dyskinesia were managed with routine medical care, such as anti-dopaminergic treatment. In the post-marketing setting, events of dyskinesia taking longer than 7 months to resolve have been observed. Immunogenicity Patients with titres of anti-AAV2 antibodies <1:1200 were allowed to participate in the clinical studies.
However, all patients that received eladocagene exuparvovec had anti-AAV2 titres at or below 1:50 before treatment. Following treatment, most subjects (n = 20) were positive for anti-AAV2 antibodies at least once within the first 12 months.
In general, antibody levels stabilised or declined with time. There was no specific follow-up program to capture potential immunogenicity reactions in any of the clinical studies, but presence of anti-AAV2 antibodies in the clinical studies was not reported to be associated with increase in severity, number of adverse reactions, or with decreased efficacy.
Experience with eladocagene exuparvovec in patients with anti-AAV2 antibody levels > 1:50 prior to treatment is not available. The immune response to the transgene and the cellular immune response were not measured. Cerebrospinal fluid leaks Three patients who received eladocagene exuparvovec in clinical studies experienced CSF leaks.
Proper aseptic techniques should always be used for the preparation and infusion of Upstaza. 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.
8). Autonomic and serotonergic symptoms of AADC may persist after treatment with eladocagene exuparvovec. Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
5 Immunogenicity Experience with eladocagene exuparvovec in patients with anti-AAV2 antibody levels > 1:50 prior to treatment is not available. 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. 8). 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.
1). 2). 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.
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Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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• After standard neurosurgical closure procedures, the patient then undergoes a postoperative brain imaging (magnetic resonance imaging [MRI] or computerized tomography [CT]) to ensure there are no complications (ie, bleeding). • The patient must reside within the vicinity of the hospital where the procedure was performed for a minimum of 48 hours following the procedure.
The patient may return home, post-procedure, based on treating physician’s advice. The post-treatment care should be managed by neurosurgeon and the referring neurologist. The patient should have a follow-up 7 days after surgery to ensure that no complications have developed.
A second follow-up visit should take place 2 weeks later (ie, 3 weeks after the surgery) to monitor post-surgical recovery and occurrence of adverse events. • Patients will be offered to enrol in a registry in order to further evaluate the long-term safety and effectiveness of the treatment under normal conditions of clinical practice.
One patient reported two separate events as serious adverse events potentially related to the surgical procedure whereas all other events were nonserious. 8 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
These handling precautions should be followed for 14 days after administration of eladocagene exuparvovec. It is recommended that patients/caregivers wear gloves for dressing changes and waste disposal, especially in case of pregnancy, breast-feeding, or immunodeficiency of caregivers.
Blood, organ, tissue, and cell donation Patients treated with Upstaza must not donate blood, organs, tissues, and cells for transplantation. Sodium and potassium content This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
This medicinal product contains less than 1 mmol potassium (39 mg) per dose, that is to say essentially ‘potassium-free’.