Rethinking Rare Disease Drug Development: How the MHRA's New Framework Could Transform Patient Access

Inside the MHRA's proposed risk-proportionate pathway for ultra-rare and bespoke therapies

Rare diseases impact more than 3.5 million people across the UK. However, fewer than 5% of these conditions have an approved treatment. Traditional clinical trials require large, homogenous patient pools — a structural requirement that is fundamentally incompatible with ultra-rare diseases or bespoke, single-family genetic variants. Generating sufficient data to support a Marketing Authorisation Application (MAA) for these medicines can be near-impossible.

To address these challenges, the MHRA has proposed a radical new framework, which introduces a highly flexible, risk-proportionate pathway designed to dismantle traditional regulatory barriers, compress drug development timelines, and accelerate patient access to life-saving treatments.

The MHRA's consultation on this framework runs until 30 July 2026.

The Core Innovation: an Investigational Marketing Authorisation

At the heart of the MHRA's draft text is the introduction of a new, modular Investigational Marketing Authorisation (IMA).

• Streamlined process: the IMA merges clinical trial approvals and marketing authorisation into a single, cohesive pathway.
• Early access: developers can secure controlled early access to the market while continuing to generate clinical and real-world evidence.
• Reduced costs: by compressing the standard 10-to-12-year development lifecycle, the IMA aims to dramatically lower development costs and boost commercial viability.
• Complementary design: the route will complement, rather than replace, existing accelerated schemes like the Innovative Licensing and Access Pathway (ILAP) and the Early Access to Medicines Scheme.

Eligibility Criteria

To qualify for the new pathway, therapies must satisfy strict eligibility criteria to prove that conventional clinical trial models are logistically impossible.

Enhanced Early Engagement and an Iterative Process

The framework is proposed to begin with an early engagement meeting — a form of scientific advice — to allow consideration of development plans and discussion of proposed clinical and real-world evidence (RWE) considerations.

Ongoing engagement would then be encouraged throughout the process, allowing iterative refinement of development plans as new data emerge.

A Rare Disease Designation step, which could also include a published Scientific Opinion, is also proposed. This provides clarity and assurance to companies to progress through the next steps of this framework.

Once granted, the IMA would be managed with a lifecycle-based, review-driven approach as further evidence is generated. When sufficient evidence has been generated, an IMA may be converted to a conventional marketing authorisation, either as an exceptional or conditional licence.

The Strategic Bottleneck: Orphan Designation Timelines

While the IMA pathway marks a progressive shift, industry experts warn that a critical administrative bottleneck remains: the UK's existing timeline for orphan designation. Under current rules, the official orphan status is evaluated and awarded only at the point of the final MAA. For companies developing potential orphan drugs, this lack of early regulatory certainty acts as a significant hindrance. Without a formal, early-stage orphan designation (as available in the EU and US), developers cannot unlock specific financial incentives in the UK during the initial development phases. This timing mismatch creates unnecessary business risk and prevents companies from achieving the best possible strategic outcomes.

Shape the Future: Your Feedback is Essential

The draft guidance represents a major step forward for the UK's advanced therapies sector, positioning the region as a highly competitive global destination for life sciences investment.

Because this framework will directly dictate how future rare disease treatments are developed, robust cross-sector engagement is vital. This is your chance to directly influence UK health policy, challenge regulatory hurdles like the orphan designation timeline, and help create a smoother pathway for cutting-edge medical science.

The MHRA is currently running an open call for feedback on the GOV.UK Consultation Hub. Pharmaceutical companies, biotech developers, clinicians, researchers, patients, and families are strongly encouraged to submit their formal responses before the 30 July 2026 deadline to ensure the final guidelines are practical, effective, and optimised for patient care.

More information on the framework can be found in the draft Rare Disease Therapies Regulatory Framework.

At regenold, we are passionate about supporting companies developing rare disease therapies — our experts can help you develop a global regulatory strategy that leverages orphan drug incentives such as orphan drug designation and early health authority engagement, as well as the more practical elements like clinical trial strategy, CTA/IND submissions, and quality services to release IMP.

As part of your regulatory strategy, our experts can help you navigate the changing rare disease frameworks described here in the UK as well as in other regions — for example, in the EU, where we will also see significant change to the orphan drug regulations in the near future.