eladocagene exuparvovec (Upstaza)

The Scottish Medicines Consortium (SMC) has completed its initial assessment of the evidence for the above product using the ultra-orphan framework:

Indication under review: 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.

Key points:

• Severe AADC deficiency is a rare genetic disorder associated with debilitating symptoms, significant impairment in normal motor development milestones, and a high risk of death in young children. Eladocagene exuparvovec is the first medicine licensed for severe AADC deficiency.
  
  
• In three open-label, single-arm studies in children with severe AADC deficiency, eladocagene exuparvovec treatment resulted in patients achieving key motor milestones (with most achieving head control and sitting unassisted); the number who achieved these key motor milestones appeared to increase over time. Total Peabody Developmental Motor Scales - Second Edition (PDMS-2) scores also improved from baseline. These suggested that improvements in motor development were deemed clinically meaningful. There were also improvements in neurological symptoms and scores that assess cognitive development.
  
  
• There are limited data available in small numbers of patients. There is a lack of efficacy and safety data for eladocagene exuparvovec in children over the age of 12 years, as well as adults. There are limited longer-term efficacy and safety data. All three studies were carried out in Taiwan, meaning generalisability to Scottish clinical practice is uncertain.
  
  
• Patients’ health related quality of life (HRQoL) could not be clinically assessed. However, carers’ HRQoL was assessed retrospectively in a subset of carers and these findings were promising. Health state utilities were also used in the economic case with appropriate values used from a sample of the general population.
  
  
• The costs of eladocagene are high relative to the expected health outcomes, and there are considerable uncertainties in the economic case which may result in the true cost of eladocagene being considerably higher or lower than the base case estimates.

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From 15 April 2024 eladocagene exuparvovec (Upstaza) can be prescribed within the ultra-orphan pathway while further evidence on its effectiveness is generated. At the end of the data collection period the company will provide an updated submission for reassessment to allow a decision on its routine use in NHSScotland.