This year, Rare Disease Day is marked on 29 February and, over the past decade, we have seen significant strides in the development of treatments for rare diseases. Despite this, many rare disease patients have no licensed treatment options and face high levels of unmet need.

A new report from the BIA, Evaluating patient access to rare disease treatments – with research provided by PwC – has assessed the progress the UK has made in providing faster and broader access to rare disease treatments and the opportunities for the UK to drive further improvements in this space.

Rare diseases are classified as diseases that impact fewer than 1 in 2,000 of the population. There are over 7,000 known rare diseases and, while individually these diseases are rare, collectively they are estimated to affect over 3.5 million individuals in the UK. People living with rare diseases face many challenges, from difficulties in getting a diagnosis to the impact on their mental health. Treatments for rare diseases can alleviate many of these challenges and in recent years we have seen some new rare disease treatments being made available to patients in the UK. Despite this progress, 95% of rare diseases have no approved treatment.

One of the challenges faced by developers of rare disease medicines is securing sustainable patient access to these treatments in different markets, including the UK. Because of the unique challenges associated with rare disease medicines, also termed ‘orphan drugs’, there are often obstacles to generating robust evidence of cost-effectiveness. These inherent hurdles are created by the low patient numbers of each disease and the difficulties that this presents in terms of the understanding and diagnosis of these diseases, as well as uncertainty around the evidence base generated from clinical trials.

The BIA’s Rare Disease Industry Group (RDIG) has been making the case for many years for changes that would help to overcome these obstacles and secure broader and faster patient access to rare disease treatments in the UK. This has involved working closely with the UK’s health technology assessment (HTA) body, the National Institute for Health and Care Excellence (NICE).

In 2019, NICE announced that it would be embarking on a wide-ranging review of its methods and processes for HTAs. To help inform the review, BIA worked with PwC to develop a report that made the case for a new way forward for evaluating medicines for rare and ultra-rare diseases in England. The report, titled A Rare Chance for Reform, identified key areas where reform would help to lift the barriers faced by orphan drugs.

‘There are over 7,000 known rare diseases and… collectively, they are estimated to affect over 3.5 million individuals in the UK’

The NICE methods review concluded in January 2022 and while it brought about some positive changes, it failed to match the ambition set out at the start of the review and the promise of a ‘high ambition’ methods review that featured in the government’s Life Sciences Vision. In particular, the specific challenge of rarity was not adequately resolved by the changes NICE introduced.

Three years on, the BIA and PwC worked together again to conduct a comprehensive assessment of the changes that have been made since the previous report was published.

These include the changes introduced by NICE in the methods review, as well as other recent initiatives to improve access to medicines. Drawing on focus groups, interviews and extensive desk research, the report presents an analysis of the progress that has been made in the UK and the challenges that remain.

On the NICE methods review, our analysis found that a number of changes had been introduced that could support improved access to rare disease treatments, including greater acceptance of uncertain evidence bases and the consideration of a broader range of quality-of-life measures. However, orphan drugs and some ultraorphan drugs continue to be assessed through the single technology appraisal (STA) process, which has a cost-effectiveness threshold of £20,000-£30,000. This compares with a threshold of £100,000-£300,000 in the highly specialised technologies (HST) process, which is used to assess ultra-orphan drugs that meet the entry criteria. As such, many orphan and ultra-orphan drugs routed to STA face significant challenges in demonstrating their cost-effectiveness under the lower threshold.

Since 2020, there have also been several other initiatives to improve access to medicines in the UK. This includes the Innovative Medicines Fund (IMF), which was launched in 2022 to provide £340m of funding per year to support faster access to innovative drugs while further data is collected through managed access agreements (MAAs). However, to date, no MAAs have been agreed upon through the IMF. Industry stakeholders have reported that one of the key reasons why the IMF is not delivering on its stated objectives is that it places a significant risk on drug companies by requiring them to continue to cover the full cost of treatment in perpetuity in the event of a negative recommendation at the end of the MAA.

For many chronic rare diseases, this could involve funding a lifetime of treatment, which in many cases would be commercially unsustainable. The BIA has called for changes to the IMF that would help to establish greater risk-sharing between industry and the NHS.

The report also looked at how the UK compares to its European counterparts, finding that the UK lags behind France and Germany on the degree of availability of treatments for rare diseases. Data from the European Federation of Pharmaceutical Industries and Associations (EFPIA)’s 2022 W.A.I.T Indicator showed that 59% of rare disease drugs approved by the European Medicines Agency (EMA) had been reimbursed in England between 2018 and 2021, as well as 55% in Scotland. This compares to 86% in Germany and 77% in France, although it ranks above Spain, at 52%.

On speed of access, drugs in England and Scotland took 398 and 488 days, on average respectively to appear on the reimbursement list following MA. While this is faster than many other comparators, including France and Spain, it is significantly slower than the average in Germany of 78 days.

Recently, both NICE and the MHRA have announced new ways to increase their collaboration with other HTA bodies and regulators to speed up patients’ access to new medicines, including through the new International Recognition Procedure. To help inform this collaboration, the report identifies successful examples of processes and schemes that help to facilitate access to rare disease drugs in comparable OECD countries that could become international best practice, including in the UK.

There are interesting examples of other marketing authorisation (MA) processes, HTA approaches and specialised schemes that help to facilitate orphan drug access.

The US is a particularly notable example of innovative MA processes, since there are a range of mechanisms in place to accelerate MA of orphan drugs, either by increasing communication with the US Food and Drug Administration (FDA), allowing earlier MA approval through surrogate endpoints, or reducing the regulatory review timeline itself through the use of priority review vouchers, which can either be granted by the FDA or purchased from manufacturers that have received it.

‘The UK has an opportunity to improve patient access to rare disease patients through the uptake of best practices both domestically and internationally’

There are a range of approaches to HTAs as well. Although Australia approaches HTAs in a similar way to NICE, it does not make use of a formal ICER threshold. This provides greater flexibility during the assessment but is perhaps at the expense of transparency in decisions. Germany and France operate HTA processes that place greater weight on the incremental health benefit of the drug, which benefits orphan drugs in particular given they often have a higher price per patient relative to other drugs and have a more limited evidence base, which can make proving their cost-effectiveness more challenging.

Additionally, there are notable examples of dedicated mechanisms to support access to orphan drugs, such as the Liste-en-Sus in France and the Life Saving Drug Program in Australia, both of which have demonstrated evidence of success in the form of providing access to a number of orphan drugs since launch.

These systems and approaches are not without their own challenges, but they provide useful context as ecosystems with elements that support access to orphan drugs. These learnings are especially important for the UK, with increasing collaboration with other regulatory and HTA bodies.

The findings in our report demonstrate that the UK has an opportunity to improve patient access to rare disease patients through the uptake of best practices both domestically and internationally. In the context of increasing international collaboration, the UK has an opportunity to demonstrate leadership in improving the lives of people affected by rare diseases. With a close network of patient advocacy groups, specialist NHS centres and clinicians, and leading scientists and academics, the UK can work collaboratively to build on the strong foundations this community has developed. The BIA RDIG is committed to working collaboratively with all stakeholders to support these efforts.

References are available on request.

Rosie Lindup is Policy and Public Affairs Manager at the BioIndustry Association (BIA)