MHRA publishes new draft rare disease therapies regulatory framework and consultation

Rare Disease Challenge: The MHRA estimates that over 3.5 million people suffer or will suffer from a rare disease in their lifetime (1 in 17 people), but only around 5% of rare diseases have an approved treatment. The Framework, developed in close partnership with the newly-established Rare Disease Consortium, is designed to streamline authorisation of therapies intended to treat conditions with a prevalence of typically 1 in 50,000 or less in the UK for which there is unmet medical needs and quantifiable barriers to conducting a clinical development programme or obtaining a standard regulatory approval.

New IMA Pathway: The new Investigational Marketing Authorisation pathway will combine clinical trial approval with a progressive route to authorisation through a series of steps between the developer and the MHRA.

Eligibility: To be eligible, the developer must demonstrate:

• the therapy targets a condition with UK prevalence in the region of 1 in 50,000 – prevalence data must be from robust sources (although the IMA pathway could be available for higher prevalence disease treatments where randomised controlled trials are not feasible);
• the severity of the condition and level of unmet clinical need (e.g., life-threatening, severely disabling, high unmet need);
• quantifiable barriers to conducting a standard clinical development programme or achieving standard regulatory approval (e.g. small and heterogeneous populations, progression data creating difficulties in defining clinical endpoints);
• its proposed development and validation methodology demonstrates efficacy; and
• agreement to the data and reporting requirements for each stage of the IMA process.

Key Steps: Obtaining an IMA will be a modular process that, subject to agreement from the MHRA, may be entered at the stage that best fits the product and the available evidence. The key steps are:

1. Early Engagement Meeting
2. Rare Disease Designation
3. Additional Scientific Advice
4. Ethics Considerations
5. IMA Application
6. Ongoing Clinical Monitoring
7. Transition to Post-Authorisation Oversight
8. Conversion to Marketing Authorisation (this will not be automatic), Restriction or Withdrawal

Benefits: Key anticipated benefits of the IMA approach are that it:

• removes the need for a discrete transition from clinical trial approval to marketing authorisation;
• permits the submission of rolling data by the developer;
• reduces complexity through better alignment between clinical development, regulatory approval, patient access, and reimbursement processes;
• supports adaptive and innovative trial designs and accepts that surrogate or patient-relevant endpoints may be appropriate if conventional endpoints are not feasible; and
• acceptance of computational modelling, digital twins, and non-animal methods where scientifically justified.

The MHRA intends the Framework to complement, not replace, existing authorisation routes such as the Innovative Licensing and Access Pathway (ILAP), conditional marketing authorisations and Early Access to Medicines Scheme.

Feedback: Manufacturers, developers, clinicians, researchers, patient organisations, carers, families and other stakeholders can submit feedback to the consultation, which closes on 20 July 2026. The MHRA is also arranging a series of general sessions over the summer whilst the consultation is underway and responses are being considered.

Final thought: The Framework will create welcome opportunities for rare disease therapy development in the UK, with a novel and innovative regulatory approach to address key clinical development and authorization challenges specific to rare disease therapies that make it difficult to apply conventional regulatory regimes designed for large patient numbers.

Authored by Jane Summerfield, Bonella Ramsay, Alexandra Wood, and Jeanne Lintonbon