The number of individuals diagnosed with a rare disease has recently increased due in part to advances in genetics and screening, however, only around 5% of rare diseases currently have an approved medicinal product. In response, the Department of Health and Social Care has extended the ‘England Rare Diseases Action Plan’ into 2027, which has four main priorities, namely faster diagnosis, increased healthcare professional awareness of rare diseases, better co-ordination of care, as well as improved access to specialist care, treatment and drugs.
Flexible licensing of medicines treating rare diseases (orphan drugs) would facilitate development and allow for faster access to treatments and drugs for people with rare diseases. The MHRA is, therefore, considering introducing a new way for UK regulation of orphan drugs and a policy paper was published on 2 November 2025 which outlined the considerations (MHRA Policy Paper). Following this, a draft of the new framework was published 21 May 2026 with stakeholder consultation that closed on 30 July 2026 (Draft rare disease therapies regulatory framework).
MHRA draft rare disease therapies regulatory framework
The current regulatory processes for the approval of medicines do not take the challenges of developing orphan drugs into consideration and the new framework aims to address this, with reform of the rare disease regulatory system expected by the end of 2026. The new legislation introduces improved and adaptable licensing processes with flexible data requirements, strengthened post-marketing surveillance and ensures patient engagement. The current orphan designation with incentives would continue to be available for developers not choosing development under the new framework.
Rare disease designation
Application and acceptance of ‘Rare Disease Designation’ under the new framework would be required and would be open to all medicines targeting therapies for conditions with UK prevalence in the region of 1 in 50,000 population. Early Engagement Meetings with the MHRA would first provide the opportunity to identify key risks and constraints of development and assess if the development of a rare treatment can be considered under the new framework. The MHRA are also considering issuing ‘Scientific Opinions’ on specific scientific, technical, or methodological aspects of a product’s development as the concluding step for Early Engagement Meetings. These Scientific Opinions would formalise the MHRA’s position, thereby reducing downstream uncertainty and supporting subsequent applications for Rare Disease Designation under the new framework.
Adaptable licensing process
For development products with ‘Rare Disease Designation’, the MHRA are proposing an early, single approval issued for both a Clinical Trial Application and Marketing Authorisation (MA) based on compelling but limited evidence. This ‘Investigational Marketing Authorisation’ (IMA) would be approved with ongoing MHRA scientific advice and Health Research Authority engagement supporting proportionate development strategies. Further MHRA Scientific Opinions would be issued throughout the lifecycle of an IMA as evidence matures. The IMA would have strict safety and efficacy monitoring including a real-world evidence review by regulators at a predefined frequency.
Flexible data requirements
Clinical studies for rare diseases can be challenging due to small numbers of available patients and often limited background knowledge of the disease. The MHRA is, therefore, considering alternative methods for generating safety and efficacy evidence in rare diseases, including the following:
- Adaptive clinical trials encompassing Bayesian statistics, N-of-1 trials, or trials proving platform technologies.
- Utilising real-world data as external controls and prior knowledge as historical controls within clinical trials.
- Utilising artificial intelligence within clinical trials.
- Employing digital and virtual models for evidence generation.
- Utilising alternative evidence sources such as patient video assessments, caregiver recorded functional tasks, wearable‑derived activity data, digital biomarkers, structured home‑based evaluations, and high‑quality natural‑history comparators.
Continuous regulatory data collection
To balance this flexible approach to licensing, long-term follow-up of safety and efficacy would be defined within a Clinical Monitoring Plan (CMP) agreed within the IMA with regular data submissions to the MHRA at a predefined frequency, triggered either at set timepoints or by patient numbers. This approach is similar to the current system for conditional MAs where there are regular mandated reviews of licence parameters. The CMP would identify known and potential risks and highlight key uncertainties in safety and efficacy.
Conversion from IMA to MA
When sufficient safety and efficacy data are collected, the IMA would convert to a conventional MA. It is anticipated that this would be either an exceptional or conditional licence, as conversion to a full MA would require a complete clinical data package that may not be possible to achieve. Once MA is granted, the usual post-marketing pharmacovigilance commitments and agreed Risk Management Plan apply. Follow-up safety data post-IMA would be collected as part of a rare disease registry or observational real world data studies.
Patient involvement in development of the framework
The MHRA is committed to consult with patients during the development of the new framework to ensure patient-centred regulation. During the informed consent process and throughout the product lifecycle, the MHRA expects Industry to provide clear and ongoing communication to patients, carers, patient organisations, prescribers and clinical teams of the uncertainties and potential risks due to limited evidence. Providing information as evidence evolves, and giving patients opportunities to ask questions, should help address the unmet needs faced by rare disease patients.
Health Technology Assessment
To enhance patient access to orphan drugs and align regulatory approvals with health system processes, engagement with Health Technology Assessment (HTA) bodies, such as the National Institute of Clinical Excellence (NICE) and the NHS is important. In February 2026, NICE published a quality standard on rare diseases, covering diagnosing, managing and treating rare diseases and high-quality care in priority areas for improvement. This quality standard should serve as a catalyst for better data collection and more consistent monitoring of the treatment of rare diseases. It states that people with a rare disease are informed about and able to access recommended treatments appropriate for their condition. Enhanced dialogue between Industry and the MHRA with NICE and the NHS would support the new rare diseases therapies regulatory framework.
How can S-cubed help you?
S-cubed are able to support clients in obtaining an Orphan Drug Designation from authoring of the scientific documentation, preparation and submission of the application through to responses to the Regulatory Agency’s questions and determination of the outcome.
Any Questions?
If you have any questions on this topic, please don’t hesitate to ask. You can contact us here, via email (info@s-cubed-global.com), and telephone (S-cubed Ltd: +44 1235 77 22 60).