MHRA consults on new regulatory framework for rare disease therapies

The Medicines and Healthcare products Regulatory Agency (MHRA) has launched a public consultation on a proposed Rare Disease Therapies Regulatory Framework that could reshape how therapies for ultra-rare conditions are developed, assessed, and authorized in the UK.

The Baseline

• The MHRA has launched a consultation on a new framework to support development of therapies for ultra-rare diseases in the UK.
• A key proposal is an Investigational Marketing Authorization (IMA), combining clinical trial and marketing authorization processes with ongoing evidence generation.
• The framework would allow more flexible evidence approaches, including adaptive trials and real-world evidence (RWE), to support earlier patient access.

The MHRA estimates that around 3.5 million people in the UK are living with a rare disease, yet only around 5% of rare diseases currently have an approved treatment. The regulator says conventional development pathways can be difficult to apply in settings characterized by small patient populations and challenges in conducting traditional clinical trials. To address these issues, it has published a draft Rare Disease Therapies Regulatory Framework and launched a public consultation, open until July 30, 2026. The proposals are intended for therapies targeting conditions affecting approximately one in 50,000 people or fewer in the UK where conventional development or approval routes may not be feasible.

A central feature of the proposal is the introduction of an IMA, a new regulatory pathway intended to combine clinical trial authorization and marketing authorization within a single framework. Under the proposed model, therapies could receive authorization based on limited but compelling evidence, while additional safety, quality, and efficacy data are generated through ongoing monitoring and regulatory review.

The MHRA said the approach is intended to support earlier patient access and provide a more continuous development pathway. Rather than relying on fixed development stages, the IMA would allow rolling data submissions, modular assessments, and structured post-authorization evidence generation.

According to the MHRA, traditional rare disease development programs typically require 10–12 years to reach marketing authorization. The agency believes earlier regulatory engagement, rolling reviews, and adaptive evidence generation could help shorten development timelines for some therapies.

The draft framework also outlines a more flexible approach to evidence generation. Proposed options include adaptive trial designs, basket and umbrella trials, natural history studies, surrogate endpoints, and RWE. The guidance also discusses the potential use of computational modeling, digital twins, and other predictive approaches where scientifically justified.

Julian Beach, Executive Director of Healthcare Quality and Access at the MHRA, said:

“Patients living with rare diseases often face significant barriers in accessing effective treatments. This consultation marks an important step towards a more flexible and responsive regulatory system that reflects the challenges and realities of rare disease development.”

Beach added that the proposed framework would provide developers with “a more streamlined and efficient process” that “supports more predictable and adaptable evidence requirements, and allows for rolling data submissions to accelerate decision-making.”

Beyond the proposed IMA, the framework also explores how platform technologies, prior knowledge, individualized medicines, and innovative manufacturing approaches could be incorporated into rare disease development programs. The MHRA notes that the framework is intended to complement, rather than replace, existing regulatory pathways, including orphan designation and other existing authorization routes.

The framework has been developed with input from the Rare Disease Consortium, which includes representatives from regulators, government bodies, NHS organizations, academia, patient groups, and industry. Feedback received through the consultation will inform the final framework and any future legislative changes required to support implementation.

Helen Knight, Director of Medicines Evaluation at the National Institute for Health and Care Excellence (NICE), stated: 

“These proposals could help to address clinical uncertainty, with the MHRA continuing stringent patient safety monitoring while NICE ensures value for money for the taxpayer.”