Final NICE rejection for Biomarin's childhood rare disease drug

After a year of negotiations NICE has confirmed that it is still unable to recommend Biomarin’s Batten disease drug, saying that the company is unable to address concerns about long-term effectiveness.

Brineura (cerliponase alfa) is designed to treat children with Batten disease, also known as neuronal ceroid lipofuscinosis type 2 (CLN2) – a very rare inherited condition affecting between one and six babies each year in the UK.

In its earlier draft guidance, published last year, NICE’s independent committee had agreed that, although Brineura is not a cure for Batten disease, it is an important development for treating the condition and it has shown substantial short-term benefits in slowing the rate at which it progresses.

But NICE said that in the negotiations since then, Biomarin was unable to price Brineura at a level that would have addressed the problems highlighted during its assessment of the drug.

Costing over £500,000 per person for each year’s treatment, Brineura is an enzyme replacement therapy administered directly into the brain via a surgically implanted permanent access device.

In the absence of long-term evidence about its effectiveness in stabilising the disease and preventing death, the independent committee considered that the drug was not value for money within the context of a highly specialised service.

The committee asked Biomarin to engage with NHS England to develop a managed access agreement to address the long-term clinical and financial uncertainties, and to negotiate with NHS England terms that could allow the drug to be made available.

“We and NHS England have been very clear with the company about what would be needed in order for us to be able to recommend cerliponase alfa,” said Meindert Boysen, director of the Centre for Health Technology Evaluation at NICE. “However, despite being given ample opportunity to come up with a workable solution, regrettably the company has not been able to do so.”

The committee concluded that it is not possible within the NHS to manage complex components of the confidential commercial arrangement proposed by the company.

“Once these elements are excluded, the cost-effectiveness estimates for cerliponase alfa are far higher than NICE normally considers acceptable for highly specialised technologies,” said Boysen.

Batten disease is a progressive condition caused by the deficiency of the enzyme tripeptidyl peptidase 1. This results in the abnormal storage of proteins and lipids in neurons and other cells, preventing them from functioning normally.

Symptoms in children with CLN2 begin from around the age of 2 and can then progress rapidly with the onset of seizures, decline in speech, loss of mobility, involuntary muscle spasms, progressive dementia and visual impairment leading to blindness.

There is currently no cure or life-extending treatments for CLN2 and clinical management is limited to symptom relief and supportive and palliative care.

The majority of children with CLN2 live to between 8 years and early adolescence; the average life expectancy is 10 years. It is estimated that in the UK there are around 30 to 50 children living with the condition.