Brexit and rare diseases: big risk, bigger opportunity?

Abstract

The UK's planned exit from the EU will leave its national health sector in a very dangerous position. It will also have profound consequences for domestic UK law. The impact may be particularly drastic for patients for whom EU law protects the right to treatment. At a particular risk are patients with rare, ‘orphan’, diseases whose treatments are uniquely enabled at the EU level. We examine the potential effects of Brexit on the orphan sector and identify an opportunity to solve long-standing and intensifying difficulties, especially the pricing of orphan drugs.

Keywords:

• Orphan drug
• rare disease
• legislation
• Brexit
• access

Introduction

The UK’s planned exit from the EU will leave its national health sector in a “very dangerous” position with reduced research funding, curtailed participation in cross-border clinical trials, possible loss of professionals who hold EU citizenship and erosion of the UK’s position as a center of pharmaceutical expertise – particularly with the removal of the European Medicines Agency (EMA) headquarters from London^1–3.

Brexit will also have “profound consequences” for domestic UK law⁴. The impact may be particularly drastic for patients for whom EU law protects the right to treatment⁵. For instance, if the UK abandons the authority of the EMA, pharmaceutical companies will need to apply to an alternative UK agency for authorization, causing “delays and difficulties” in accessing drugs⁶. Pharmaceutical companies are likely to focus on the EU and other markets, putting any UK regulator in a weak bargaining position.

Our particular concern is for patients with rare, “orphan”, diseases whose treatments are uniquely enabled at the EU level. We examine the potential effects of Brexit on the orphan sector and identify an opportunity to solve long-standing and intensifying difficulties, especially the pricing of orphan drugs.

What will happen to EU law upon Brexit?

Should the UK give notice of its intention to withdraw from the EU, there is a two-year period in which negotiations must be completed³. Thereafter, all rights of the UK and its citizens under the EU treaties vanish unless the UK Parliament adopts legislation covering those rights. This task is so monumental that the government has expressed an intention to convert all existing EU law into domestic law and subsequently “amend, repeal and improve” as it sees fit⁷. But achieving this outcome is not certain, for Parliament has the sovereign power to veto any such proposal.

UK orphan legislation following Brexit: three scenarios

The EU orphan drug regulation 141/2000 bestows a 10 year marketing exclusivity. This gives a manufacturer time to recoup the costs of bringing a drug to market. The monopoly thus intends to stimulate the development of drugs for patients with rare diseases in which there would otherwise be little commercial interest.

If the regulation ceases to apply, the UK will no longer recognize orphan drug designations (which are a prerequisite for gaining a marketing monopoly), and an orphan drug manufacturer’s monopoly will end in the UK. Competing drugs could then enter the market. As a funder of treatments the UK government might welcome downward pricing pressure. However, the downsides would seem to outweigh any gain: there will be uncertainty, drugs may be pulled from the UK market to avoid downward price referencing and access to treatment could be at risk. Taking a longer view, should further countries leave the EU, the exclusive market will shrink and eventually remove the incentive for developing orphan drugs altogether. This would fundamentally jeopardize the industry and laudable intent behind the regulation.

Perhaps a better option would be for the UK to adopt the orphan regulation wholesale with orphan drug authorizations continuing to be delegated to the (rehoused) EMA, or an equivalent UK body that coordinates with the EMA and issues accelerated approval after the EMA or FDA have done so.

However, we contend that Brexit also presents an opportunity for a third way: adopting the regulation’s essentials such as the marketing exclusivity, but with refinement. The central focus in this regard is the price of orphan drugs. Neither the EU regulation, nor its US equivalent, sets a cap on prices. Member states have attempted to control prices. For example, in the UK, the National Institute for Health and Care Excellence (NICE) recently adopted a conditional approval mechanism which revisits efficacy and price after five years⁸.

But individual member states’ ability to negotiate is limited, and the high cost of orphan drugs remains a mounting challenge worldwide. This generates further distress for patients who fear withdrawal of treatment due to its cost, as well as the industry, whose reputation is damaged by the perception of greed.

Brexit presents an immediate opportunity for improvement of a system, ostensibly introduced for the benefit of patients and the economy but which has outgrown itself – threatening its sustainability. Amended legislation would enable the pricing of orphan drugs to be controlled definitively according to principles by which particular characteristics of orphan medicines are taken into account.

Indeed, the pharmaceutical industry now appears keen to “rebrand” itself as a trustworthy health partner and sees itself as at an inflection point, moving away from traditional business models (based on highest possible price) to alternative revenue models. These include flexible pricing structures linked to the ability to pay and streamlined research and development to lower launch prices⁹.

Ensuring access to medicines is now considered essential by 12 of the top 20 pharmaceutical companies in the Access to Medicine Index, which measures access in low- and middle-income countries¹⁰. This shift may reflect the increasing pressure of emerging markets demanding access to treatments and the reality that their governments cannot afford monopoly pricing set for wealthier states.

Conclusion

An apparent motive for the vote to leave the EU was perceived unfairness and the sense that the individual had been left behind¹¹. Ironically, the orphan example shows that Brexit has the risk of hurting the most vulnerable: patients. They must have continued access to vital therapy.

Continuity is also critical for the orphan biopharmaceutical industry, for which the UK is a key market; a large portion of EU orphan drug revenue comes from the UK¹². Most of the 7000 rare diseases are currently without a treatment, and the EU legislative scheme remains central to the development of treatments for the millions of Europeans who suffer from them.

This is the moment to create an improved orphan legislation. Brexit, or the threat of change related to Brexit, offers the means by which parties can embrace the much trumpeted “transformational leadership” in the orphan field. Patients, physicians, government and industry representatives, as well as leading legislative drafters, now have the opportunity to build on over 30 years’ experience of orphan legislation and deliver an improved version for the UK. To this end, we will publish our own orphan price-setting model shortly.

The opportunity should also appeal to the ambitions of the UK and NICE to lead in the global health care sector. Mid- and lower-income countries could use such a blueprint for their local legislation to alleviate the plight of their own citizens suffering from rare diseases, many of whom are currently denied any treatment.

The UK government is currently focused on broader aspects of Brexit and its tractability; rare disease legislation has likely been given less thought. However, it would be economically unwise – and immoral – to repeat the historic neglect of rare disease patients which the regulation corrects. The win–win principle of orphan drug legislation needs restructuring that will lead the world well ahead of Brexit.

Transparency

Declaration of funding

This editorial was not funded.

Declaration of financial/other relationships

HI Hyry and JCP Roos have attended symposia and received hospitality or funding towards attendance or related research from the UK Gaucher Association, Susan Lewis Memorial Fund, Helen Manuel Foundation and the European Working Group on Gaucher disease. JCP Roos has also received support from the National Institute for Health Research. TM Cox has received support from the UK Medical Research Council and the National Institute for Health Research as well as unrestricted research grants from Genzyme and Shire. TM Cox also advises pharmaceutical companies engaged in the orphan disease setting, including Actelion, Genzyme, Shire, Amicus Therapeutics, and Protalix Biotherapeutics, receiving speakers? fees and travel costs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.