Girl loses High Court battle over NICE review of BioMarin’s PKU drug


An 11-year-old girl with the rare disease phenylketonuria (PKU) has lost a legal battle in the High Court over a decision by NICE to deny NHS access to the only approved drug in the UK.

The legal team representing Gail Cotter of Chelmsford in Essex challenged NICE in the courts over its decision to review BioMarin’s PKU therapy Kuvan (sapropterin) using its standard appraisal process, rather than its Highly Specialised Technology (HST) programme.

HST gives much more flexibility on cost when considering whether new drugs are cost-effective for NHS use, raising the threshold for cost-effectiveness from £30,000 per quality-adjusted life year (QALY) to £100,000.

Lawyers for the family argued that Kuvan would have been recommended for NHS use if it had an HST review, that NICE’s decision to use its standard process for the drug was “irrational”, and that there should be a judicial review of the appraisal process.

In return, NICE’s counsel maintained that it was possible for Kuvan to get a green light under the standard process if BioMarin was prepared to move on the price it would charge the NHS for the drug. However that became impossible because the drugmaker withdrew its drug from the appraisal process.

The defence argued that “in practice manufacturers are often willing to offer very substantial discounts to the NHS, sometimes as much as 80% off list price, because the NHS is such a big customer,” according to court documents.

The High Court dismissed the application for a judicial review, concluding that it was “not irrational”, after hearing arguments from both sides on a complex set of technical issues.

That included whether the target patient group for Kuvan is “distinct for clinical reasons” and could be selected for treatment with the drug, and whether it would be delivered only through a “highly specialised service” via very few NHS treatment centres.

The judge in the case – Mr Justice Cavanagh – concluded that “in an ideal world, there would be no restrictions on the availability on the NHS of very useful drugs such as Kuvan, but we do not live in an ideal world.”

 “It is NICE's responsibility to decide which drugs to recommend for use in NHS England, against the background of a finite budget,” he continued. “This means, unavoidably, that NICE must make difficult decisions which will disappoint people who have every good reason to hope that a drug or treatment will be recommended for use.”

PKU – caused by an inability to metabolise the amino acid phenylalanine in the diet – is currently managed with a combination of a stringent dietary regime that avoids foods like eggs, meat, fish and cheese, along with artificial protein and amino acid supplements and blood tests.

Without strict controls, the amino acid accumulates in the body and can lead to irreversible brain damage.

Kuvan replaces an enzyme that is deficient in PKU patients, reducing what is generally a massive burden on families to meet the dietary restrictions, whilst also reducing the risk of brain damage.

The verdict was greeted with dismay by Eric Lange, chairman of the National Society for Phenylketonuria (NSPKU), who said: “The NHS has accepted that Kuvan is a safe and effective drug for PKU.  It is completely unacceptable that the UK is one of the only countries in the world where this treatment is unavailable.”

Lange added: “We urge BioMarin and the NHS to work together to get a deal for patients as soon as possible. Both sides need to resolve this situation urgently.”

The case was viewed as a pivotal challenge of NICE’s handling of rare disease drugs, which according to the charity Genetic Alliance UK is “opaque” and needs reform.

Speaking a few weeks back, its chief executive Jayne Spink pointed out that NICE guidance has been published on only eleven rare disease medicines since 2013 using HST, which is “a fraction of the number of drugs licensed for rare conditions in that period.”