The National Institute for Health and Care Excellence (NICE) has issued draft guidance that recommends Kuvan (sapropterin), alongside a low-phenylalanine diet, for treating children younger than 18 who have phenylketonuria (PKU).
NICE estimates that about 75 children with PKU in England would be eligible for treatment, out of a total eligible population of about 308 people.
The draft guidance is open for comments through March 16. The committee will meet to consider the responses on April 7.
“Sapropterin [Kuvan] allows patients to manage their condition more easily, reduces symptoms, and provides peace of mind about blood phenylalanine levels,” Meindert Boysen, said in a press release. Boysen is deputy chief executive and director of the Centre for Health Technology Assessment at NICE.
PKU is caused by mutations that impair the body from breaking down an amino acid called phenylalanine. This causes phenylalanine to build up in the body, which can cause irreversible brain damage, especially in children.
Typical management for PKU is a low-phenylalanine diet, which restricts intake of most natural proteins (such as fish, meat, eggs, cheese, seeds, pulses, bread, flour, and pasta), together with dietary supplements.
Kuvan, by BioMarin, is designed to help lower phenylalanine levels by stimulating the enzyme that breaks down this amino acid. The goal of treatment with Kuvan is to reduce phenylalanine levels in the body, allowing dietary restrictions to be relaxed as much as possible.
According to the NICE committee, evidence from clinical trials demonstrates that Kuvan treatment reduces blood phenylalanine levels in people with PKU. However, because only short-term evidence is available, there is some question as to how well the therapy works. For example, the committee was uncertain to what extent Kuvan can reduce the reliance on a low-phenylalanine diet.
NICE also pointed to a difficulty in estimating the treatment’s cost effectiveness due to limitations with the economic analyses presented. Nonetheless, the committee acknowledged that Kuvan could prevent long-term and irreversible brain damage in children.
Accounting for the benefits and costs of treatment, the committee concluded that Kuvan in children with PKU is likely within the range that NICE considers an effective use of National Health Service (NHS) resources.
“Even though the evidence for a substantial reduction in the protein-restricted diet is lacking, when combined with concerns for long-term irreversible brain damage and impact on quality of life, [Kuvan] can be recommended as an option in children, alongside a protein-restricted diet,” Boysen said.
Childhood is a critical period for brain development, which is why children with PKU are at more risk of long-term brain injury than adults. Adults also require a higher dose of the therapy than is used for children.
Because of these factors, along with uncertainties about how much Kuvan reduces the need for a phenylalanine-restricted diet, the lack of data on quality-of-life improvements, and limitations of the cost effectiveness analyses, Kuvan treatment in adults was not deemed a cost-effective use of NHS resources.
“Because of the weight-based dosing, and without the effect assumed for children, there is very limited scope for the drug to be considered cost-effective in adults,” Boysen said.
A possible exception, Boysen noted, is the use of Kuvan during pregnancy, since PKU can cause damage to a developing fetus if the condition is poorly controlled. However, the committee was unable to make a recommendation on the use of Kuvan during pregnancy because of a lack of data. The committee requested more evidence in this population to be considered at its next meeting.
“We urge the company to work with us to try to find constructive solutions to the uncertainties highlighted in the draft guidance, particularly where it concerns [pregnant people],” Boysen said.