From Trendy to Timeless: Sustaining Patient Access to Rare Disease Therapies in a Shifting Landscape

A striking aspect of this year’s ISPOR Europe conference was the limited discourse specifically from a rare disease perspective, perhaps with the exception of the poster sessions. This is particularly remarkable given that rare diseases account for approximately 40% of Food and Drug Administration (FDA) approvals and 20% of European Medicines Agency (EMA) approvals,¹ and given that advanced therapy medicinal products (ATMPs) will be initial candidates for Joint Clinical Assessment (JCA) from the beginning of 2025. It may reflect a change in focus for key opinion leaders in the rare disease space to other forums, such as Health Technology Assessment International (HTAi), where a new rare diseases special interest group has been formed and has set ambitious research goals. However, it’s also clear that the challenges of health economics and outcomes research (HEOR) and HTA within rare indications are not currently a “trendy” topic.

The rare perspective on the JCA hot topic

Nonetheless, many of the key themes of this year’s conference were still relevant to the rare disease community. One of the many issue panels on JCA during the conference aimed to give voice to the opinion of those working in rare diseases on the new European Union (EU) HTA process.² The session successfully summarised key challenges around evidence generation to meet JCA requirements, primarily the need to provide direct comparative evidence (ideally through randomised trials. However, the session didn’t provide practical solutions to manufacturers.

In the short term, our priority recommendations for clients facing evidence generation challenges in rare disease populations are to:

• Participate in scientific advice as early as possible, ideally through the Joint Scientific Consultation (JSC) process, but also at a national level. This will help to ensure planned evidence generation activities meet both JCA expectations and local payer needs
• Conduct pragmatic PICO scoping exercises from an early stage, to support evidence generation planning to meet priority PICOs. Our research suggests that pragmatic PICO scoping exercises, for example relying on clinical guidelines (where available) to determine relevant subpopulations and treatments, can go some way to identifying relevant PICOs
• Make a robust and compelling case within the JCA dossier for where evidence requirements (as per current JCA guidance) are infeasible to meet within the relevant population. No assessments/decisions on clinical benefit will be made during the JCA process, but creating that narrative within the JCA dossier will form a strong groundwork to support local negotiations later on

JCA will employ a strict and narrow framework for clinical evidence requirements. In the longer term, a framework that recognises the evidence generation challenges that are inherent in small and heterogenous populations — and that offers flexibility on the requirement to meet all PICOs (when evidence generation is challenging at the best of times) — would be more feasible for manufacturers. Giving additional consideration under JCA of broader elements of value would better reflect the benefits these treatments offer. This is particularly important for products targeting conditions with substantial unmet needs and often limited or no effective treatment options, as it would better recognise the value for individuals, families, and caregivers.

Are we preparing for changing European and US market dynamics?

Looking outside of Europe, the implementation of the US Medicare Drug Price Negotiation Program potentially is likely to influence decision making around product portfolios and indication sequencing.³ This change could trigger a decline in the pursuit of rare disease indications in the US. Companies are likely to prioritise larger indications for drugs with multi-indication potential, as the Inflation Reduction Act (IRA) Orphan Exemption will only apply to drugs approved for a single orphan indication.³ In some ways this mirrors changes in the European environment. Our colleagues, Annabel Griffiths and Tom Gleeson, reflected after ISPOR Europe 2023 that the upcoming reform in EU pharmaceutical legislation — specifically the alterations in incentives and attenuated market exclusivity assurances — may deter companies from launching rare disease products in the EU (see here).

There is a fundamental truth that financial incentives drive innovation. The historic success of orphan drug incentives illustrates how financial rewards have propelled investments in therapies for rare diseases. With reducing incentives, we are at risk of underinvesting in scientific advancements with long-term benefits for patients with rare diseases.

Where should those of us working in the rare disease space focus our efforts?

It was clear from discussions with our collaborators that willingness to develop innovative medicines for rare diseases remains. However, fostering creativity with and advancements in HEOR and market access approaches remains fundamental in sustaining patient access to rare disease therapies:

• Let’s focus on stakeholder collaboration and continue to recognise where different stakeholders can bring greatest value. For example, changing models are being explored for the development of innovative and high-cost therapies for ultra-rare populations, such as non-profit led commercialisation of gene therapies.⁴ This does not represent an “ideal” solution in the long-term, but shows that progress can be made by approaching problems from a different angle
• Let’s continue to share learnings around the latest HEOR methods. For example, we can lead the way in patient engagement and the use of patient experience data,⁵ which is so crucial for understanding the experiences of individuals with rare diseases. We can continue to lead the way on methods for quantifying caregiver quality of life impacts, to ensure the benefits of new treatments for families and other caregivers are recognised within health-care decision making. And we can continue to drive discussions around the use of surrogate outcome measures, and external control arms, often the only options available for assessing the efficacy of new treatments in rare populations

References

1. Kamerikar, V; Dheer, P; Seoane-Vazquez, E. A Comparison of Orphan Drugs Approved by the FDA and EMA, 1995-2022. Available here. Last accessed: December 2024.
2. ISPOR Europe 2024. Panel Session 304: Giving Voice to Rare Diseases During Joint Clinical Assessment. Slides available here.
3. ISPOR Europe 2024. Panel Session 108: How will Europe’s Pharmaceutical Policy and HTA Stakeholders Respond to Medicare Price Negotiation? Slides available here.
4. ISPOR Europe 2024. Panel Session 230: Is It Time for More Non-Profits to Lead Reimbursement and Commercialisation of Gene Therapies to Promote Affordable and Sustainable Access? Overview available here.
5. Beacon for Rare Diseases. What are rare diseases? Available here. Last accessed: December 2024.
6. ISPOR Europe 2024. Panel Session 128: Co-Creating a COA Strategy with Patient Partners: Guidance, Good Practice Methods, and Case Examples. Slides available here.