MHRA proposes new regulatory pathway for rare disease therapies

The Medicines and Healthcare products Regulatory Agency (MHRA) has opened consultation on a rare disease pathway aimed at speeding therapies to patients and asking industry to help shape the final framework.

The draft sets out a technology-agnostic regulatory framework, meaning it is intended to work across different therapy types, to address scientific, evidence and commercial barriers that can prevent rare disease therapies reaching patients through conventional development models.

It is designed for therapies targeting rare diseases with a prevalence of typically around one in 50,000 people or fewer in the UK, where there are clear and measurable barriers to conventional development.

The consultation runs until 30 July and seeks input from pharmaceutical companies, biotech developers, contract research organisations, academics, clinicians, patients and carers to support earlier access to potentially life-saving therapies.

Public health minister Sharon Hodgson said: “For the millions of people in the UK living with a rare disease, and for the families and carers who support them, the search for effective treatment can be long, exhausting and deeply uncertain.

“These landmark proposals represent an important step towards a more agile and compassionate system, one that recognises the unique challenges of rare disease research while maintaining the highest standards of patient safety.”

The consultation gives industry a direct opportunity to shape the final guidance, including eligibility criteria for an Investigational Marketing Authorisation, known as an IMA, the use of real-world evidence, scientific advice processes and how the framework would work alongside existing routes such as orphan designation and the Innovative Licensing and Access Pathway.

The framework has been developed with input from the Rare Disease Consortium, a cross-sector group including the MHRA, the Health Research Authority, NICE, the Department of Health and Social Care, NHS England, patient advocacy organisations, academia and industry partners.

The MHRA said early engagement meetings will be encouraged and that general sessions will be arranged over the summer while the consultation is under way and responses are considered.

Traditional rare disease programmes typically take 10 to 12 years to reach marketing authorisation, driven by linear phase progression and limited opportunities for early regulatory involvement.

At the centre of the proposal is a new IMA.

The IMA would combine clinical trial approval with a progressive route to marketing authorisation, rather than requiring sponsors to move from trial approval to marketing authorisation as separate regulatory steps.

Marketing authorisation is the approval needed before a medicine can be made available for use.

The proposed model would support rolling data submissions, modular assessments and earlier patient access where there is limited but compelling evidence, backed by structured post-authorisation evidence generation for safety, quality and efficacy.

The proposed framework is intended to shorten timelines, particularly in early development and regulatory decision-making.

It also supports adaptive and innovative trial designs, including basket trials, umbrella trials and hybrid studies using real-world evidence.

The guidance says surrogate or patient-relevant endpoints may be appropriate where conventional endpoints are not feasible.

Surrogate endpoints are indirect measures, such as a biomarker, that can indicate whether a treatment is likely to benefit patients.

The MHRA also said it is open to the use of computational modelling, digital twins and non-animal methods where scientifically justified.

For larger pharmaceutical companies, the MHRA said the guidance could create opportunities to diversify into very rare indications with more iterative investment strategies and a more predictable regulatory environment.

For smaller developers and academics, it said the framework could provide earlier regulatory certainty and structured scientific advice from the outset.

Julian Beach, executive director of healthcare quality and access at the MHRA, said: “A single authorisation removes the need for a discrete transition from clinical trial approval to marketing authorisation, supports more predictable and adaptable evidence requirements, and allows for rolling data submissions to accelerate decision-making.

“It also promotes better alignment between clinical development, regulatory approval, patient access, and reimbursement processes, thereby reducing complexity.”

“By working closely with patients, partners and industry, we’re building a framework that supports innovation while maintaining the high standards of safety that patients expect.”

“Industry feedback is vital to this consultation, so please share your views through the consultation.”

Helen Knight, director of medicines evaluation at NICE, said: “The MHRA’s proposed Rare Disease Therapies Regulatory Framework potentially complements NICE’s approach that enables NHS patients to receive innovative and promising medicines while additional evidence is gathered on how well they work in practice.

“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.

“We support the ambition to improve timely access to rare disease therapies and look forward to engaging in more detail alongside wider system partners to ensure this delivers safely for patients, value for the NHS and aligns with broader government policy objectives.”