• Phenylketonuria (PKU) is a rare metabolic disease resulting in raised
blood phenylalanine levels which can reach neurotoxic concentrations.
The condition is characterised by poor neurocognitive and neuromotor
development with subsequent impairment of intelligence and social
functioning. Management is by dietary restriction of phenylalanine.

• There are likely to be between 30 and 80 patients within NHS North East
who might be suitable and eligible for treatment with sapropterin for PKU.

• Sapropterin is the first drug treatment available for PKU. It is an epimer of
an endogenous enzyme substrate. Clinical studies in paediatric and adult
patients have demonstrated that for some patients it can lead to important
reductions in blood phenylalanine levels.

• The clinical studies of sapropterin used an enriched patient selection
process which will reduce the validity unless this can be replicated in
practice. A common outcome measure was the proportion of patients
achieving a reduction of 30% in phenylalanine levels from baseline. This
rate has been arbitrarily selected and in practice the proportion of patients
achieving a specific target is likely to be of greater interest.

• Safety data from relatively short-term studies do not indicate any important
safety concerns with treatment. Most adverse effects consist of a mild
gastrointestinal type, or headache.

• Sapropterin is designated an orphan drug. It is an expensive treatment,
with typical annual costs in the range £20,000 to £50,000 depending on
the actual dose. This is several times more expensive than usual
management with special dietary foods and supplements. Sapropterin is
unlikely to meet conventional criteria for cost-effectiveness in terms of cost
per quality adjusted life year.

• The drug will be supplied at no cost until the patient response has been
determined (28 days supply). The drug will be preferentially supplied to
patients via homecare arrangements at no additional cost.

• There are some special populations that may potentially gain greater
benefits from treatment, for example in maternal PKU, or young patients
with poor control despite dietary intervention. Studies in these groups
specifically have not been conducted.