Working together to bring hope to more patients with rare diseases

Pulmonary arterial hypertension (PAH) is a rare disease affecting around 7,000 people in the UK. It is an incurable and progressive illness that affects the blood vessels supplying the lungs, making it harder for the heart to pump blood there. Eventually, patients can struggle to breathe, even at rest.

Left untreated, the prognosis is poor with an average life expectancy after diagnosis of two to three years. Thankfully, advances in PAH treatment have had a dramatic effect, with seven-year survival increasing from around 30 per cent to 60 per cent.

Dr Gerry Coghlan, who developed the pulmonary hypertension service at the Royal Free Hospital in London, says: “Being able to access medicines that help to slow the progression of the disease allows patients and their carers to live a normal life for as long as possible.”

However, many PAH patients in England struggle to get the right medication and treatment when they need it, says Dr Coghlan. “Access is based on measures that don’t really reflect the latest evidence and current understanding of PAH,” he says. “The system is really struggling.” For people living with the condition, quick access to the right medicines is a matter of life or death.

By working together, the NHS, patients, clinicians and the research-based pharmaceutical industry can create a system that works to the benefit of people affected by rare conditions

PAH is an exemplar of the current landscape for the treatment of rare diseases in the UK. Scientific advances in our understanding of rare diseases such as PAH have led to a wave of medicine innovation, offering new hope to patients. The number of medicines being developed and approved in Europe for treating rare diseases is increasing every year. Also new initiatives, leading to earlier diagnosis, are enabling treatment to start sooner, bringing hope to people affected by the condition.

But public health systems like the NHS are struggling with the rising number of applications for funding. The regulatory system has evolved to encourage the development and availability of medicines to treat rare conditions, but NHS funding processes are struggling to keep pace and make them rapidly available to patients.

The systems for deciding what medicines will be funded for use on the NHS vary around the UK, with different bodies tasked with assessing whether new medicines represent good value for taxpayers’ money. In England this responsibility lies primarily with the National Institute for Health and Care Excellence (NICE). In Scotland the role is taken by Scottish Medicines Consortium and in Wales by the All Wales Medicines Strategy Group.

Assessing the value for money of medicines developed for small groups of patients has a number of innate challenges. Most new therapies for rare diseases will have small patient populations and may have few existing treatments with which they can be compared. Although NICE is internationally recognised as a gold standard in assessing the value of medicines, its standard methods were designed nearly 20 years ago for different types of medicines, for larger groups of patients.

Because of these challenges, Scotland and Wales have recently amended their reimbursement processes for rare diseases. One key change made by them emphasises the importance of both the patient and the clinician’s experience of treating, or living with, rare conditions which decision-makers may often not be familiar with. The assessment processes also take into account issues around interpreting data, which can only be obtained from small patient populations.

In England there are two main mechanisms when a new medicine for a rare disease is assessed by NICE. Firstly, the same technology appraisal process used by NICE to assess conditions with larger patient numbers can be applied. This can be problematic when looking at medicines to treat smaller patient numbers as cost effectiveness, which NICE assesses, can be difficult to quantify.

Secondly, the Highly Specialised Technologies programme, which was specifically designed for patient populations of around 500 people or fewer across the country, can be used. This programme recognises challenges inherent in standard NICE processes being used for assessment of medicines in conditions with small patient populations. However, most medicines for rare conditions are not eligible for this programme.

NICE currently uses a one-size-fits-all evaluation approach by applying a fixed cost-effectiveness threshold to judge all medicines. But the NICE Quality Adjusted Life Years threshold in standard technology appraisals can be discriminatory for evaluating some medicines for rare diseases, due to limited data and uncertainty in the figures produced when there are small patient numbers.

The good news is that NICE has committed to undertaking a review of its methods over the next year. This is a major opportunity for patients and other stakeholders to engage and ensure meaningful change can be delivered for rare disease patients.

Jayne Spink, chief executive at Genetic Alliance UK, says: “Patient groups and clinicians feel that in populations with a rare disease, where there are small groups of patients, there should be a more holistic interpretation of value, as in Scotland through its orphan medicines process.”

A solution is needed for the medicines that are not suitable for assessment using methodologies designed for larger patient populations and which are not eligible for assessment under NICE’s Highly Specialised Technology programme. These medicines are currently falling between cracks in the system.

New approaches between pharmaceutical innovators and the NHS are likely to be needed, which address some of the uncertainty about the cost effectiveness of medicines for small and very small groups of patients.

Drawing on international examples, the UK could seek to provide patients with access to life-changing treatments as close to them being licensed and made available to patients as soon as possible. Any data gaps could then be filled by gathering real-life experience to generate the additional cost and impact data that might be required, and to enable further assessment, incorporating this real-world data, at a later date. This type of conditional reimbursement is already practised for some cancer medicines.

Carina Righetti, director of market access and external affairs at Actelion UK, concludes: “Novel approaches like these could help patients with rare diseases by giving them faster access to new, transformative treatments. The system must also be future-proofed to ensure that it can respond to scientific innovations.

“By working together, the NHS, patients, clinicians and the research-based pharmaceutical industry can create a system that works to the benefit of people affected by rare conditions.”

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