Those of you that know me, will know I am passionate about supporting the rare disease eco-system. In my previous role at NICE, I was given the task of updating NICE’s Highly Specialised Technologies (HST) topic routing criteria. It was no easy task I can tell you. Since that time, I’ve had many conversations where the criteria have been criticised for not being broad enough as well not being clear enough for stakeholders to understand and interpret.

Responding to this feedback, The National Institute for Health and Care Excellence (NICE) acted in December 2024 when they held a consultation with the objective of clarifying the criteria. As a result, the NICE board approved some refinements, which took effect on April 1, 2025. NICE Public Board March 2025. These criteria are crucial for deciding which treatments for ultra-rare diseases get evaluated under the HST Programme, a pathway designed to tackle the unique challenges of developing and accessing therapies for ultra-rare patient populations. Working out which topics to select for the HST programme has always been challenging because while healthcare may be a science, these decisions have, in my mind, always been an art meets science situation. I’ve always said, “Be careful what you wish for…”

In this article, I have summarised the updated criteria and explored what I believe will be the potential impact on rare disease therapies, the patient community, the life sciences sector and the wider UK market.

The guidance states that technologies will be considered eligible for routing to the HST Programme if the NICE prioritisation board agrees that all four routing criteria have been met:

1. Ultra-rare and debilitating diseases

The disease must have a prevalence of 1 in 50,000 or fewer in England and cause lifelong debilitating symptoms that severely impact patients and their families. There are 2 parts to this criterion:

Routing criterion 1A focuses on defining the ultra-rare disease by ICD-11 codes itself, identified through clinical exams, patient history, or tests available in the NHS (England). This criterion is not about the disease symptoms.

Routing Criterion 1B addresses the characteristics of the ultra-rare disease. This identifies those diseases that are lifelong requiring continuous clinical management or support, as well as have an exceptional negative impact—meaning the disease significantly shortens life or severely affects quality of life. This will be judged on a case-by-case basis.

2. The technology is an innovation for the ultra-rare disease

Innovation refers to new or advanced treatments (e.g., ATMPs, new chemical/biological entities, or novel drug-device combos) that offer added health benefits compared to current options.

Repurposed, extended-use or multiple indications for technologies are excluded.

“In my opinion we all want innovation, and it means different things to different people. But by excluding repurposed products and restricting multiple indications within the HST programme it risks neglecting ultra-rare disease populations with significant unmet needs. Repurposing existing treatments—especially when they could benefit related ultra-rare conditions with similar co-morbidities—potentially offers a cost-effective and practical solution but requires substantial investment to prove they work in an ultra-rare disease population. Without a viable pathway to recoup these costs, developers may shift focus to new, more expensive drugs, the NHS cannot afford.  These policies not only deter innovation but also limit treatment options and unfairly disadvantage ultra-rare populations, where generating robust evidence is particularly challenging and alternative therapies are often unlikely to emerge.”

3. No more than 300 people in England are eligible for the technology in its licensed indication, and the technology is not an individualised medicine

‘Eligible’ refers to all individuals in England who could receive the technology under its marketing authorisation. The technology must be intentionally developed specifically for a small, ultra-rare disease population and be the first licensed treatment for that condition. It should not be an indication extension from another disease or subgroup and is unlikely to apply to other subgroups beyond the initial target population.

“Excluding treatments for sub-populations of ultra-rare diseases is unacceptable and risks blocking access to potentially beneficial therapies. If companies see no viable route to commercialisation, these diseases could miss out on incremental treatment advances, improved care quality, and valuable disease insights. This approach contradicts the UK Rare Disease Framework and discourages investment and research in ultra-rare conditions. Given the limited understanding of these diseases, rigid criteria such as “unlikely to be suitable for other subgroups”, overlook the complexities involved and risk creating further inequities.

4. The technology is likely to offer substantial additional benefit for people with the ultra-rare disease over existing established clinical management and the existing established clinical management is considered inadequate

‘Substantial additional benefit’ refers to a technology that significantly improves life expectancy or quality of life for people with an ultra-rare disease, supported by clinically relevant data (e.g., PROMs). A technology qualifies if no other disease-modifying or symptom-targeted treatment is available in the NHS for that specific ultra-rare condition at the time of assessment. This assumes that if there is a therapy that is ‘disease-modifying’ or ‘symptom-targeted’ then that is good enough, therefore there is no need for anything new for that ultra-rare disease. So again, no opportunity for incremental improvement or learning for ultra-rare disease.

“The refined criteria encourage innovation by prioritising therapies targeting ultra-rare conditions with no effective treatment options. This could drive investment in cutting-edge technologies like gene therapies and ATMPs. However, the restrictive nature of the criteria may exclude promising treatments for rare diseases that do not strictly meet these thresholds, potentially limiting patient access.”

Conclusion

The HST Programme offers vital hope to patients with ultra-rare conditions by enabling access to transformative treatments and addressing unmet needs often overlooked by standard processes. However, the revised criteria raise concerns about reduced access, missed opportunities for treatment development and the UK slipping down the global launch order—an outcome neither patients nor the life sciences sector want.

From an industry standpoint, while the HST Programme reinforces the UK’s ambition to lead in rare disease innovation, its increasingly restrictive framework may deter investment and product launches. New eligibility barriers—especially for repurposed or multi-indication treatments—risk undermining the programme’s original intent. With clinical trial activity already down 52% in two years, these changes could further weaken the UK’s appeal as a destination for ultra-rare disease research, development and launch. ABPI report

The refinements to NICE’s HST routing criteria reflect a delicate balancing act between promoting access to therapies for ultra-rare diseases and managing NHS resources effectively. While they bring greater clarity and predictability, their restrictive nature may unintentionally exclude innovative treatments and limit access for the very population the programme was designed to support. It’s hard to walk back from such decisions, but as the saying goes, the proof is in the pudding—so we must closely monitor the impact on ultra-rare communities and ensure meaningful feedback informs future adjustments.

---

About Sheela – a life sciences consultant specialising in rare disease

Sheela Upadhyaya is a consultant to the life sciences industry. She previously led the NICE Highly Specialised Technology Programme, the programme to evaluate medicines and technologies for rare and ultra-rare conditions for commissioning in the NHS. In her consulting practice she supports a range of strategic activities to advance rare diseases from research all the way to access and adoption.

Sheela excels in developing partnership and collaboration-enabling change and progress. In her consultancy, she works with a range of stakeholders on policy and market access issues in the rare disease space. She possesses an excellent ability to challenge the status quo with stakeholders to secure positive access and adoption for orphan medicinal products.

She is co-chair for the Health Technology Assessment International Rare Disease Interest Group and is chair in a project at ISPOR (The Professional Society for Health Economics and Outcomes Research) in rare disease.

---

Sheela can be contacted at sheelaupadhyaya@gmail.com, or connect with her on LinkedIn.

---