Years Later, Families in England are Still Fighting for NHS Coverage of Batten Disease Drug

Families in England affected by Batten disease are struggling to access effective treatments in their home country.

Nicole and Jessica Rich are two young girls who live with their families in Newcastle, in the far north of England — just about an hour’s drive from the Scottish border. They also both have Batten disease, a rare neurological condition that can be extremely difficult to treat. Until last year, both had been receiving cerliponase alfa in institutions in London and Hamburg, Germany. That is, until NICE (the National Institute for Health and Care Excellence) ruled that cerliponase alfa hadn’t proven sufficiently effective in treating its target patients, and recommended against National Health Service funding of the treatment.

About Batten Disease

Batten disease” is a bad nickname, because “Batten disease” is actually a group of closely related but highly rare neurological diseases more properly called neuronal ceroid lipofuscinosis. Yes, I can see why “Batten disease” stuck — for brevity’s sake, I will continue to refer to it as such.

There are four main types of Batten disease. Each type has a unique genetic mutation associated with it, giving rise to differing symptoms and ages of onset. Most subtypes first show symptoms in early childhood, though adults can sometimes be affected. Despite their differences, however, most forms of Batten disease are similarly characterized by seizures, loss of vision, delayed development, and eventually the loss of previously acquired skills, dementia, uncontrolled movement, and early mortality.

It is estimated that as many as 4 children in every 100,000 are born with, or develop, some form of Batten disease. Currently, no treatment exists that has been proven to halt or reverse the symptoms of Batten disease, though some treatments can provide palliative benefits. One such treatment is cerliponase alfa, sometimes called by its trade name, “Brineura.”

About Cerliponase Alfa (Brineura)

Brineura is made by BioMarin Pharmaceutical, an American biotechnology company based in California. It received its first approval from the American Food and Drug Administration (FDA) in early 2017, and then received another approval, this time from the European Commission, just a few months later.

In both cases, Brineura was approved on an expedited basis, receiving approval through the FDA’s priority review and the European Commission’s accelerated assessment pipelines. These paths to approval exist to direct administrative attention to drugs that, if approved, could significantly improve on the safety or effectiveness of existing treatment methods.

Brineura is designed for patients with CLN2 disease, a subtype of Batten disease that typically shows its first symptoms in late infancy or early childhood (ages approximately 6-7). Patients with CLN2 are deficient in an enzyme called tripeptidyl peptidase 1 (TPP1), an enzyme that plays a general role in breaking down larger proteins into their constituent amino acids. Because of patients’ low levels of functional TPP1, proteins start to accumulate in their cells, eventually creating significant health concerns. CLN2 patients frequently develop seizures, before gradually losing the ability to walk and speak. Eventually, patients may require a feeding tube and rely almost entirely on their caretakers. Mortality is expected between the ages of 6 and 12 for most cases.

Brineura is an enzyme replacement therapy, delivering laboratory-synthesized TPP1 enzymes to CLN2 patients. The treatment is delivered through intraventricular infusion — meaning the enzymes are piped directly into the brain through a reservoir called an intraventricular access device that is surgically implanted in the skull. Every other week, patients receive a recommended 300mg infusion, followed immediately by electrolyte infusion through the same port. The process takes about 4.5 hours each time.

The stated purpose of the drug is to slow the loss of walking ability in late infantile CLN2 patients 3 years of age and older. The therapy is expensive, as many orphan drugs are — carrying a shocking annual price tag of over $700,000.

NICE Argues Against Brineura

When the Rich family was told NICE would not be recommending Brineura for the NHS, they were at a loss. Regular trips between clinical trial sites in London and Hamburg had already proven to be exhausting. Now the family had to deal with the fact that their national healthcare system disagreed with the cost-effectiveness of Brineura.

NICE acknowledged that Brineura had proven to be effective in providing short-term relief of ambulatory function loss, but argued that there was insufficient “long-term clinical evidence” of the drug’s effectiveness. NICE added that, due to this lack of clinical evidence, “assumptions about long-term disease stabilization and mortality” were uncertain. In light of this, and the $700,000 price tag, NICE recommended against NHS coverage of the drug.

Families affected were shocked, and many more were outraged. “Children with Batten Disease do not have time,” a post on the Nicole & Jessica’s Batten Journey Facebook page noted. BioMarin does have a long-term safety study planned to assess Brineura over a minimum of 10 years, but for children with Batten disease, that’s most of a lifetime.

The reality is that NICE doesn’t want to pay for NHS distribution of Brineura without long-term data. However, for the Riches, that means the annual cost of almost $1.5 million for their daughters’ treatments would be almost entirely on them. Other families like them are caught in no-man’s land as well, waiting for something to budge. As you may have guessed, most simply discontinue treatment.

NICE refusing to recommend Brineura for NHS coverage seems poorly considered, in light of the fatal nature of CLN2. The evaluation of risk posed by a drug versus its potential benefits is a guiding principle of early access programs that exist in the United States and Europe, so there is absolutely a precedent that potential long-term safety risks are of lesser concern than potential clinical benefits — especially when weighed against the life expectancy of a fatal illness.

What it really seems to come down to is cost. NICE doesn’t believe that the quality of life benefit afforded by Brineura is worth the $700,000 price tag. It’s hardly the first time it’s happened, as well — NICE have recommended against NHS coverage of several other rare disease drugs in the last ten years alone, all on the basis of cost-effectiveness.

As the Rich family point out, however, the annual cost of Brineura is offset by the rareness of Batten disease, and especially CLN2. “If they did pay the [now £550k] which is the top marketed price, with 17 children that’s £8.5million per year,” or roughly $10 million. “That would be 0.0012% of the NHS budget.”

If you think Brineura should be covered by the National Health Service, you can sign this petition to make your voice heard. If you live in the United Kingdom, there may be other ways you can help. As always, you can share your thoughts with Patient Worthy!

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