A faster route to rare disease treatments: the MHRA’s proposals 

Of an estimated 10,000 rare diseases, the vast majority still have no effective therapy, according to the Medicines and Healthcare products Regulatory Agency (MHRA), which puts the cost of delayed diagnosis at £340m per year and health-related disability costs at a further £4.7bn.

However, up to 3.5 million people in the UK living with rare diseases could access treatments more easily via a new framework proposed by the MHRA in May 2026.

The regulator puts the current route to marketing authorisation of rare disease therapies at 10–12 years, but its proposals promise earlier licensing and would bring more treatments into a regulated pathway rather than being used ‘off-label’, as many are at present.

“The government’s proposals to bring more treatments for rare diseases into a regulated pathway could improve patient experience by creating a clearer route for developing and authorising vital new treatments for this group,” says Alice Billin, head of policy and public affairs at the charity Cystic Fibrosis Trust.

In the consultation, the MHRA said its proposed ‘Rare disease therapies regulatory framework’ would incorporate a compressed regulatory pathway “expected to reduce the cost of developing rare disease therapies and potentially make medications more affordable”. 

Central to the proposal is a new Investigational Marketing Authorisation (IMA) pathway, which would combine clinical trial approval with what the MHRA calls a “progressive route” to market authorisation approval. This means that “where there is limited evidence, patients could gain access to innovative treatments earlier, subject to approval by the National Institute for Health and Care Excellence (NICE) on NHS use”, the MHRA says. 

Helen Knight, director of medicines evaluation at NICE, says the 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”. 

“NICE look[s] 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.”

The framework would apply to conditions that NICE categorises as “ultra-rare or ultra-orphan diseases”, affecting fewer than 1 in 50,000 people where there are quantifiable barriers to conducting a ‘standard’ clinical trial. Entry to the proposed new pathway will be guided by criteria such as the severity of the disease and unmet need. 

This threshold has already drawn objections. PSC Support — a charity for those with primary sclerosing cholangitis (PSC), a rare, immune-mediated liver disease affecting only around 5.6 to 10 in 100,000 people — has raised concerns about the threshold for inclusion in the new framework, noting that it risks excluding diseases such as PSC. In a statement on its website, the charity says it “strongly supports the MHRA’s new framework to speed up access to rare disease treatments, but we oppose excluding PSC based on an arbitrary prevalence cut-off”. 

However, the MHRA adds: “While the framework is primarily intended for rare diseases, elements of it… may also be relevant to conditions with higher prevalence where randomised controlled trials are not feasible or are impractical.”

Current guidance and off-label use

Conventional regulatory guidance for therapy approvals is typically designed for common diseases and assumes large patient populations, validated clinical end-points and phase III confirmatory trials. 

Although some rare disease therapies can be approved based on clear clinical benefit from small trials, the MHRA proposals highlight several challenges to this, including:

• “Apparent modest efficacy signals due to slow disease progression, small and heterogeneous populations, or the absence of a control arm”;
• “The impracticality or infeasibility of randomised controlled trials in very small populations”;
• “Urgent unmet medical need that may be incompatible with the timelines of traditional development programmes”; 
• “Where traditional development models may not be sustainable given limited patient numbers and uncertain returns on investment”.

Those barriers are a large part of why many people with rare diseases are treated with medicines used outside their licence — and why the MHRA is proposing a regulated alternative.

There is no separate legal category or national pathway for off-label prescribing in rare disease. Instead, General Medical Council guidance on off-label/unlicensed prescribing allows any UK doctor to prescribe a licensed medicine outside its marketing authorisation, or an unlicensed medicine altogether, where they judge it to be in the patient’s best interests on the available evidence. In rare disease practice, that tends to happen at a local, specialist level.

In its response to the MHRA’s public consultation, the Royal College of Pharmacy (RCPharm) accepted that off-label prescribing can be clinically necessary but warned “reliance on off-label use may result in variable evidence standards, inconsistent patient information, uncertainty around dosing and monitoring, and less structured pharmacovigilance”. 

“A regulated pathway has the potential to provide greater clarity on indication, quality, safety monitoring, benefit-risk assessment, prescribing responsibilities, patient communication and data collection,” it added.

Licensing is only half the picture: whether a patient receives a treatment depends on who commissions it. Specialised services for people with rare and, historically, complex conditions have been planned and paid for at a national level by NHS England. However, in the past few years, NHS England has sought to involve local integrated care boards (ICBs) more in their commissioning, meaning those decisions are increasingly taken locally.

New authorisation method

The IMA is the MHRA’s attempt to bring that off-label activity inside a licensed framework. It says the mechanism would improve patient experience by shortening the 10–12 years it typically takes a rare disease programme to reach marketing authorisation.

The regulator says this would enable rigorous safety assessment and support controlled patient access. And, because it is a form of marketing authorisation, it would allow use of the drugs while evidence continues to mature. 

The IMA would not replace the ‘Early access to medicines scheme’, which does not focus on therapies for rare conditions, but it would need legislation to allow its introduction.

The framework sets out an eight-step process for IMA to be granted, and there would be fees attached for drugs manufacturers wanting to channel their products through this route.

Pharmacy involvement

In its response, RCPharm said it supported the principle of bringing more pharmaceutical treatments for rare diseases into a regulated pathway “where this can be achieved without creating unnecessary barriers to timely access”.

The College also stressed that “the role of pharmacy teams should be made explicit” in the use of treatments for rare diseases. 

“Pharmacists and pharmacy professionals are central to medicines optimisation, procurement, storage, preparation, dispensing, administration governance, monitoring, adverse drug reaction reporting, patient counselling and safe transitions between specialist and local care,” it added. 

These will be “particularly important for advanced therapies, individualised medicines, repurposed medicines and therapies requiring long-term follow-up”.

What happens next

The consultation closed on 30 July 2026, and the MHRA has said it will run engagement sessions over the summer while responses are considered.

However, Billin warns that the pathway “should support, not limit, appropriate off-label prescribing when this remains the best or only option and the framework must also set clear expectations for when and how patients will be involved and how their contributions will shape decisions”. 

“Ultimately, the pathway will only improve patient experience if it leads to treatments people can access,” she says.