UK rare disease therapies rulebook to be overhauled

The UK Medicines and Health products Regulatory Agency (MHRA) will publish a new regulatory framework for rare disease therapies in 2026, aimed at reforming the UK development and approval processes for rare disease treatments.

The UK MHRA has recently detailed in a position paper, its intentions to “design a forward-looking framework that meets the needs of patients with rare diseases, while ensuring robust evidence generation, system sustainability and international convergence.” The proposed new regulatory framework aims to transform the lifecycle of rare disease therapies by addressing their unique challenges.

Patients with rare diseases often face significant unmet medical needs due to factors such as limited scientific understanding of their condition as well as small, dispersed patient populations. Within the UK, approximately one in 17 individuals lives with a rare disease, yet only 5% of these conditions have approved treatment options.  

CASGEVY approved for use on the NHS in England

The National Institute for Health and Care Excellence (London, UK) has approved CASGEVY (exagamlogene autotemcel) for use on the NHS in England for patients who are aged 12 and older with a severe form of sickle cell disease.

Developing therapies for rare diseases is particularly challenging. Each new rare therapy requires its own regulatory approval process, including obtaining approval to initiate clinical trials and securing a license to market the therapy in the UK. Conducting clinical trials and collecting sufficient evidence to demonstrate a treatment’s effectiveness is especially difficult when working with small patient populations. 

Other challenges arising from conventional regulatory pathways, which are primarily designed for common diseases, include: 

• Unclear or unvalidated endpoints due to limited natural history data. 
• Lengthy development timelines that conflict with unmet patient needs. 
• Unique manufacturing and long-term safety concerns, particularly for advanced modalities such as cell and gene therapies. 

To address some of these challenges and support the UK Government’s broader life sciences strategy and Rare Diseases Action Plan, the revised regulatory framework will streamline testing, manufacturing and approval processes, making the development of rare disease therapies faster and more accessible for patients. 

Currently being explored, the rulebook may include: 

• Introducing the option for an early, single approval covering both a clinical trial application and marketing authorization, based on compelling but limited evidence. A strict safety monitoring plan and scheduled reviews of real-world evidence would accompany this approval. 
• Enhancing evidence-sharing within the UK and globally to better pool scarce data. 
• Exploring whether a single approval could be granted for therapies with variable components tailored to individual patient characteristics. 
• Emphasizing the importance of strengthened post-market surveillance. 
• Improving health system alignment both in the UK and internationally. 

While the new rulebook is not expected to be published in full until 2026, the position paper outlines the current approach taken by UK regulatory partners.  

“For too many families, a rare diagnosis comes without a viable cure or treatment. This program is a vital step towards changing that. Fostering the development of treatments here in the UK will bring direct benefits for people living with rare conditions,” commented Nick Meade, chief executive of Genetic Alliance UK (Bristol). “We welcome this clear signal of the UK’s commitment to becoming a world leader in rare condition therapy development, and our community of rare condition organizations stands ready to lend its expertise to make it a success.” 

Consultation on the framework is set to begin in early 2026, with the goal of developing a refined and implementable model by late 2026.

Policy paper: rare therapies and UK regulatory considerations