fosdenopterin (Nulibry)

Indication under review: for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A

Key points:

• MoCD Type A is a rare, rapidly progressive, chronic, fatal inherited metabolic condition, characterised by a deficiency in molybdenum cofactor (MoCo). This results in a build-up of sulphite in the brain and leads to irreversible neurotoxicity, with symptoms including seizures, feeding difficulties, missed developmental milestones, psychomotor abnormalities, and neurological impairment.
  
  
• Fosdenopterin is a substrate replacement therapy which restores MoCo-dependent enzyme activity and reduces accumulation of neurotoxic compounds. Evidence from an integrated efficacy analysis suggested that fosdenopterin is associated with benefits in outcomes such as overall survival, normalisation of urine S-sulfocysteine (SSC) levels, and median time to sustained non-oral feeding.
  
  
• The clinical evidence was limited by small sample size, retrospective/observational and prospective/interventional studies that are prone to bias, and differences in baseline characteristics and dosing. There is therefore uncertainty in the magnitude of benefit of fosdenopterin.
  
  
• If given early enough, fosdenopterin may offer the potential for patients to participate in normal daily activities. Whilst patients receiving fosdenopterin may not be able to engage with activities to the extent of healthy persons, quality of life may be improved compared to those who do not receive fosdenopterin for MoCD Type A.
  
  
• The health economic evaluation indicated that fosdenopterin is associated with a discounted quality-adjusted life year (QALY) gain of 9.96 QALYs compared to standard of care. However, limitations including issues of utility values, outcome data, overall survival extrapolations and model structure increased uncertainty in the economic results. The treatment’s cost in relation to its health benefits is high.

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Scottish Government Medicines Policy Branch will notify Health Boards when this medicine is available for prescribing within the ultra-orphan pathway.  Meantime any requests to access treatment should be considered through local non-formulary processes.