Refreshing the rare disease therapies regulatory framework in the UK

PHG Cambridge (as PHG Foundation) has submitted its response to the MHRA’s consultation on the new Rare Disease Therapies Regulatory Framework. Below, Bhavya Krishnan, who led on PHG Cambridge’s response, considers three questions industry still needs answered

• How will the Medicines and Healthcare products Regulatory Agency (MHRA) ensure these approvals lead to patient access?
• How will exclusivity protect patient access while rewarding genuine innovation?
• What are the implications for the clinical genetics community and wider worksforce?

How will the Medicines and Healthcare products Regulatory Agency (MHRA) ensure these approvals lead to patient access?

One thing that stood out to me whilst drafting the response is the gap between authorisation and funded access: these are two separate decisions, made by two different bodies, on two different sets of criteria. The consultation itself is candid about this – an Investigational Marketing Authorisation does not guarantee reimbursement.

This gap matters more in rare disease than almost anywhere else in medicine. These are often single-supplier, high-cost treatments with no competing alternative. That means a funding decision has an inflated effect on whether a patient can actually get treated, in a way it simply doesn’t for conditions where multiple treatment options exist.

There is real reason for optimism. NICE’s standard cost-effectiveness threshold rose in April 2026 for the first time in around two decades, and the severity modifier introduced in 2022 already pushes the effective threshold for the most severe conditions up to roughly £50,000 per QALY. For very rare diseases, the Highly Specialised Technologies route allows an even higher threshold, between £100,000 and £300,000 per QALY. In principle, this should let more rare disease therapies clear the cost-effectiveness bar than before.

However, the Highly Specialised Technologies route has narrow entry criteria. Many rare disease products will still end up being assessed through the standard route instead, where the benefit of a higher threshold isn’t guaranteed. The tools to make more rare disease treatments viable exist, on paper. In practice, the routing between them isn’t joined up.

Faster authorisation without joined-up appraisal risks creating a two-tier system, where some rare disease patients benefit from these reforms and others don’t, purely depending on which route their treatment happens to go through. That’s really the crux of my concern, not simply whether the science is good enough to approve a treatment, but whether the right patients actually go on to get it.

For context on the scale of the underlying problem, only around 1 in 20 of the UK’s 7,000-plus recognised rare conditions currently has an approved NHS treatment. Over the past six years, the UK has dropped from 2nd to 11th place in European rankings for orphan medicine availability. In a recent industry survey, 11 of 18 pharmaceutical companies said they expect to launch less than 75% of their rare disease pipeline in the UK over the next five years, citing the low likelihood of a positive NICE reimbursement decision as a key reason.

Faster approval is genuinely good news, but can’t be allowed to simply move the bottleneck from the regulator to the payer.

How will exclusivity protect patient access while rewarding genuine innovation?

In our response to the Medicines and Healthcare Products Regulatory Agency (MHRA) consultation we ask MHRA to tie exclusivity terms to demonstrated clinical advance, not administrative reformulation, and to design exclusivity policy jointly with reimbursement policy from the outset.

As it stands the draft framework doesn’t have very much to say on the topic of  market exclusivity. Yet market exclusivity matters more for rare diseases than perhaps any other group of conditions.

When a treatment has exclusivity, no competitor is allowed to enter the market, hence there is no competition  to bring the price down. For common conditions, that’s usually temporary. Exclusivity is time limited and, once it ends generics or biosimilars typically arrive. But for rare diseases, the patient population is often too small to attract that competition at all. Prices can stay high well beyond the exclusivity period itself, because there’s no one else in the market to challenge them.

That makes exclusivity design a significant access issue, not just a commercial one. For patients with no alternative treatment, a long or poorly calibrated exclusivity period can be the difference between funded access and years of waiting.

There’s also an evergreening risk specific to this framework. Since the evidence bar for an Investigational Marketing Authorisation (IMA) is deliberately lighter than for a standard marketing authorisation, it can be easier for a minor product adaptation, such as a new formulation, dosing schedule, or delivery method, to be packaged as a “new” rare disease therapy and win a fresh exclusivity period, without delivering any real benefit to patients.

This connects to something else worth flagging. One of the stated aims of this whole framework is to bring more rare disease treatments into a regulated pathway rather than leaving them used off-label. However, simply creating that pathway doesn’t automatically achieve that, because off-label use isn’t really a regulatory problem. It’s a stability problem – a clinician and patient sticking with an established off-label treatment, rather than one newly authorised through an IMA, is often a rational choice if the newly authorised product’s long-term availability looks less certain.

Additionally, there are real, currently unanswered questions behind that uncertainty. What happens to a patient already being treated if an IMA is later revoked, does their treatment simply stop? If a product doesn’t go on to secure a full marketing authorisation after time on an IMA, what continues to incentivise the developer to keep manufacturing and supplying a drug for what may be a tiny patient population, once the commercial case for doing so has weakened? Without clear answers, an IMA doesn’t remove the incentive to stay off-label, it just adds a second, less familiar route that carries its own risks.

In our response to the MHRA consultation we ask MHRA to tie exclusivity terms to demonstrate clinical advance, not administrative reformulation, and to design exclusivity policy jointly with reimbursement policy from the outset, so genuine innovation is rewarded and access isn’t quietly closed off in the process. It also needs to set out, clearly and in advance, what continuity of care looks like for a patient if a product’s authorisation status changes, and what would keep a developer commercially committed to supply even where full conversion to a marketing authorisation doesn’t happen.

Encouraging faster development is the right instinct. But it can’t come at the cost of leaving exclusivity design as an afterthought.

Workforce capacity and clinician buy-in

The MHRA’s new rare disease framework offers real opportunity for it in the clinical genetics community, and rightly so, but translating it into delivery will come down to efficient workforce integration.

Most rare diseases have a genetic cause, and clinical geneticists and genetic counsellors are usually the ones interpreting the test results, and working out whether a patient is eligible for one of these newly developed rare disease therapies. They’re not a downstream support function, they’re the route most patients will need to go through before this framework becomes relevant. That puts this workforce right at the centre of the opportunity the framework creates.

It also means getting the integration right matters more than almost anything else in making this work. Genomic testing volumes have grown fast as whole genome sequencing is rolled out across the NHS. Services already have to make careful judgement calls about when a rapid turnaround is genuinely needed, as with NICU and PICU genome sequencing. Streamlining how clinicians triage and prioritise this kind of work, so capacity goes where it has the most impact, will be a key part of making this framework deliverable alongside everything else already on their plate.

Better-connected systems would help enormously here. Genomic testing labs, clinical genetics services, research teams and NHS registries don’t always share data smoothly across the four UK nations, and closing that gap would free up real clinical time currently spent on admin.

Additionally, the framework’s shift toward ongoing consent, rather than a one-off conversation, is a positive step for patients, but it will ask more of clinicians’ time and communication skills, repeatedly, as a treatment’s evidence develops. Upskilling as part of the wider mainstreaming of genomics is part of the answer, and training that’s consistent across services will matter too, so that patients get the same quality of consent conversation wherever they’re seen.

None of this works without clinicians at the table from the start. The best way to find workable solutions is through collaboration with the people delivering the service, not a top-down resourcing plan alone, since they’re best placed to know where training, streamlining and integration will make the biggest difference in practice.

This blog was first published on LinkedIn as a short series of articles expanding on our submitted response to the MHRA consultation on its draft rare disease therapies regulatory framework