Rewriting The Rulebook: MHRA's Vision For Rare Disease Therapies

A new policy paper released on 2 November 2025 sets out the MHRA's proposals on overhauling and transforming the UK regulation of rare therapies.

The intention is for a "bold new rulebook for rare therapies" to be published in 2026. Rare therapies is defined as medicinal products intended to treat rare diseases, specifically, conditions with a prevalence of no more than 5 in 10,000. The Medicines and Healthcare products Regulatory Agency (MHRA)'s press release on the matter provides the concerning statistic that, while ≈3.5 million people in UK are affected by rare diseases (equivalent to one child in every classroom), and many more if carers are taken into account, only 5% of rare diseases have approved treatment. An intention of the reform is therefore to shorten the time for development of therapies for such conditions from initial discovery through to the stage of delivery to patients.

The MHRA aims to position the UK as a global leader in developing, regulating, and integrating rare therapies into healthcare. This policy paper outlines a new regulatory framework designed to accelerate access to innovative treatments for rare diseases while maintaining safety and evidence standards.

The initiative is supported by the newly formed Rare Disease Consortium, a collaborative effort made up of various different stakeholders including the MHRA, NICE, DHSC, NHS England, as well as patients and their representatives, academia and research institutions and industry.

A draft of the framework is anticipated to be available by Spring 2026, with external review in the first half of the year. A public consultation will also be conducted in 2026.

Current barriers for rare therapies

Recent advances in science and technology are enabling highly personalised treatments for rare diseases, including gene-based therapies like CRISPR and mRNA. These can be tailored to specific patient subgroups, and in some cases, even to a single individual based on their genetic profile.

Despite this progress, several barriers remain, including:

• Limited patient populations and data make traditional trials difficult in the rare disease space, with long diagnostic delays further hindering access.
• Urgent patient needs vs. slow regulatory processes, compounded by limited use of real-world data and minimal patient involvement in shaping frameworks.
• Complexity of advanced therapies, such as bespoke gene treatments, which pose challenges in manufacturing, safety, and approval.
• Gaps in post-market surveillance, including the need for robust registries and international data sharing to support long-term monitoring and global progress.

Overview of policy paper

The MHRAis taking bold steps to transform how rare therapies are developed, evaluated, and delivered. The policy paper outlines a forward-thinking framework aimed at accelerating access while maintaining safety and scientific integrity. The policy paper refers to the application of "a proportionate and adaptable licensing process" and emphasises the need for ongoing dialogue with relevant decision makers to ensure that the new framework aligns with Health Technology Assessment (HTA) and NHS processes in order to maximise uptake.

The MHRA's key proposals include the following.

1.Scope and criteria for pathway

New regulatory pathways to accelerate access to rare therapies, starting with rare diseases affecting no more than 5 in 10,000 people (described as a consultation starting point – not a strict exclusion).

MHRA intends to develop pragmatic entry criteria and decision tools, that can accommodate both highly individualised treatments and those for small populations. These tools will help guide regulatory decisions, simplify evidence requirements, and align with international standards.

2.Prior knowledge

The MHRA sets out its aim of expanding the type of evidence to support regulatory decisions for rare therapies, referring in particular to real-world data, in-silico trials (computer based simulations), and Artificial Intelligence (AI)/ Machine Learning (ML) models. A key focus is on leveraging prior knowledge from related products and technologies to meet clinical evidence requirements, especially where traditional trials are impractical.

Regulatory tools and guidance will be developed addressing the points set out below.

• Defining prior knowledge, across quality, clinical, non-clinical and statistical aspects and how different data sources can be weighed in evidence generation to support regulatory submissions.
• Addressing platform definition challenges in three main contexts: disease area, non-clinical, and manufacturing, recognising the need for flexibility and clarity on terminology and expectations.
• Risk-based and stage-appropriate application, based on a balance of benefits and risks, considering disease severity, patient population size, and stage of product development.
• Tiered approach, based on the type of rare disease according to the difficulty or challenges in generating sufficient data to support a study.
• Guidance on referencing of prior knowledge sources in regulatory dossiers, defining platform technologies, appropriate use of master files, and providing direction on how such data should be weighed in evidence generation to support regulatory decisions.

3.Novel Registration and Licence Structure

The MHRA is designing a flexible, proportionate licensing framework to support the particular challenges of rare therapy development. Central to this is a new pathway for an investigative marketing authorisation that bridges clinical trials and standard marketing authorisation processes. Proposals include:

• Investigative Licensing Pathways: MHRA may grant early approvals based on limited but scientifically grounded evidence – such as a plausible mechanism of action – with ongoing reassessment as more data becomes available.
• Flexible Evidence Approaches: Surrogate endpoints, natural history comparators, and real-world data will be considered when traditional trial methods are not feasible, enabling more adaptive and inclusive evidence generation.
• Pre-Designation Dialogue: Before entering the pathway, developers must engage in a structured discussion to clarify product details, evidence plans, and lifecycle management. This ensures alignment from the outset and allows for future reviews as needed.

To reduce regulatory burden and accelerate development, the MHRA is exploring the use of source files and shared data across developers, enabling broader use of prior knowledge in quality, clinical, and non-clinical domains. A structured pathway – beginning with formal designation and involving multi-agency collaboration – will guide trial design, ethical considerations, and access strategies. The investigative marketing authorisation model also proposes modular data submissions, real-world evidence collection, and conditional approvals, alongside proportionate manufacturing and supply requirements. Accreditation of specialist centres and safeguards for data sharing will ensure patient safety, regulatory integrity, and commercial viability.

4.Post market surveillance

The MHRA intends to strengthen post-market surveillance for rare therapies to ensure long-term safety and effectiveness. This includes establishing national rare disease registries to collect real-time, longitudinal patient data, implementing risk management plans that evolve with emerging evidence, and promoting international data sharing to supplement small UK cohorts.

A longer-term goal is to align post-marketing data requirements across regulatory and HTA processes. This could involve managed access agreements, biomarker-based approvals, and flexible, case-by-case surveillance strategies.

5.Embedding Patient and Public Involvement

The MHRA sets out a commitment to place patient expertise at the centre of its rare disease regulatory reform, working closely with patient groups across all workstreams. Patients will contribute to regulatory development, licensing decisions, and the creation of guidance, ensuring transparency around investigational approvals and ongoing monitoring. The Rare Disease Consortium will guide this work into 2026, supported by a comprehensive involvement plan and continued engagement through workshops and collaborative outputs.

6.Global Harmonisation and alignment with UK health system

The MHRA is working to align UK regulatory pathways for rare therapies with international standards, recognising that global collaboration is essential to address shared challenges. This includes supporting scientific development across academia, the NHS, and industry, with international convergence a key focus for 2026.

Domestically, the MHRA is coordinating with UK health system partners to ensure consistent access across all regions, aligning regulatory and HTA processes early, and supporting delivery of the England Rare Diseases Action Plan. These efforts aim to streamline development and access to rare disease therapies across the UK and beyond.

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