World Orphan Drug Congress EU 2023: How can we maximise opportunities in the evolving European rare diseases landscape?

As regular attendees of the World Orphan Drug Congress (WODC) Europe, Costello Medical were delighted to sponsor this year’s conference held in Barcelona with five members of our rare diseases team in attendance. We also hosted our first roundtable at the congress to discuss and debate the findings from our ‘Maximising the Value of Expert Judgement in Rare Disease’ survey (further details can be found here).

This instalment of the annual conference proved to be the biggest yet, bringing together over 1,500 attendees from different areas of the healthcare sector. In this post, my colleagues Isabelle Newell , Emma Warnants , Juliet Johns , Faye Bolan and I summarise our key thoughts and takeaways from the meeting.

How could the new EU legislation proposals be modified to create a more attractive market for orphan drug manufacturers?

One of the major talking points of the congress, and focus of a number of plenary sessions, was the proposed reform of the European Union (EU) pharmaceutical legislation (Figure 1).

The reforms will constitute the first major revision of EU legislation in 20 years, presenting a major opportunity to ensure Europe continues to be seen as a competitive market in the orphan drugs landscape. Attendees were generally positive about proposals to cut the EMA market authorisation pathway from 210 to 180 days, representing an opportunity to grant quicker access to medicines for patients with rare diseases, a population for whom high unmet need necessitates faster access pathways. However, representatives from both pharmaceutical and public bodies voiced concerns that the EU is lagging behind the US in terms of attractiveness as a launch market, and ease of access for patients.

Modulation of incentives and weakening market exclusivity assurances within the reforms were considered likely to dissuade companies from launching in the EU, due to increased uncertainty in the incentives they could receive. The European Federation of Pharmaceutical Industries and Associations (EFPIA) recently published a press release stating that Europe risks losing a third of its of research and development due to the new legislation.[1] Based on our experience with product launches, there is a lot to be gained from certainty in any regulatory/market access pathway, and therefore these changes are likely to dissuade a considerable number of products from the EU.

The need for manufacturers to demonstrate that a condition has ‘high unmet need’ in order to be eligible for just six additional months of market protection is associated with inherent subjectivity, and requires high levels of resource to generate sufficient evidence. In light of this, and the two-year deadline for a comprehensive EU launch in order to gain an additional two years of regulatory data protection, it is likely that greater numbers of small-medium enterprises (SMEs) who typically have limited resource will move away from Europe. This is a real concern, particularly given that SMEs are often founded on the basis of innovative scientific technologies and cutting-edge breakthroughs. Consideration must be given for how the legislation can better support SMEs, to avoid resource intensive activities disproportionately preventing them from accessing incentives at a time when they are needed most.

The EU Commission (EC) could consider learnings from their UK neighbours at the National Institute for Health and Care Excellence (NICE) who have selection criteria as part of their highly specialised technologies (HST) programme, including a criterion for significant unmet medical need. The NICE criterion can be demonstrated by ‘no satisfactory treatment options’ being available or if ‘the technology is likely to offer significant benefit over existing treatments’.[2] In line with the concerns from industry, research conducted by Costello Medical in collaboration with Pharming Group N.V. has shown that this unmet need criterion has been most difficult for manufacturers to demonstrate. However, where products have met this criterion, in all cases they have achieved it by demonstrating that no satisfactory treatment options exist – this may be a more ‘specific’ definition of unmet need that the EC could use, and might offer the certainty that industry are looking for.[3]

ERNs: Where Europe is establishing a global lead

Exciting developments were shared around European Reference Networks (ERNs), which are comprised of more than 1600 healthcare units and 400 hospitals across Europe, collectively treating around 16 million people with rare diseases. The scheme was established to connect doctors and researchers to share expertise on rare diseases and to generate knowledge through research. No other market has a network like the ERNs, and there is a huge opportunity through the ERNs for Europe to further accelerate research and become global leaders in collection of real-world data.

One of the congress streams was dedicated to the Together for Rare Diseases (Together4RD) initiative, a multi-stakeholder initiative launched in 2021 to support collaboration between ERNs and industry. Their recently published position statement discussed barriers, both tangible and perceived, to ERN-industry collaboration and plans to alleviate these barriers to address research needs. At WODC, stakeholders involved in the first ERN-industry pilot studies shared insights and progress to date (ERKNet and EuroBloodNet). Individuals involved in these pilots commented on the challenges of managing conflicts of interest, organising governance and data ownership, and ensuring transparency. Nevertheless, the tone from both panellists and audience members was optimistic. We are in full agreement with the impactful comment from Graham Slater (board of directors of EURORDIS) that the risks associated with public-private partnerships were well known and could be mitigated for; on the other hand, there are 30 million possible benefits of advancing ERN research, corresponding to the number of people living with a rare disease in the EU.

Public engagement as the solution to the expansion of NBS?

Though newborn screening (NBS) is supporting improvements in the rare disease ‘diagnostic odyssey’, variability in the number of conditions included on NBS panels is contributing to inequity in access to life-saving treatments. With some countries like the UK requiring robust data and lengthy procedures to add new conditions to the panel, the key role patient groups play in advocating for NBS and sharing learnings between countries is clear. However, in several panel discussions NBS was considered a wider public health issue; if the public knew that treatments could be accessed more quickly through NBS, perhaps governments could be convinced to expand NBS panels, to see greater uptake of NBS (akin to the 98.8% uptake rate in the UK). It is clear that efforts to expand NBS therefore need to be accompanied by adequate social policies and engagement with the general public.

A new era for gene therapies

While payment models for high-cost gene therapies are still debated, several examples of these now exist due to the launch of a number of gene therapies over the last few years. One of the more common payment models uses outcome-based payments, whereby payment is made to the gene therapy manufacturer when a certain clinical outcome is achieved. However, there are concerns that this approach may no longer be sustainable in the long-term. With a greater number of gene therapies expected to launch in the coming years in both rare and more common conditions, there are questions about whether payers will have enough budget to reimburse numerous high-cost gene therapies.?

Due to concerns regarding outcome-based payment methods, a number of different, innovative payment models have been discussed. One of these is a warranty model, whereby gene therapy manufacturers collaborate with third-party insurance companies to provide a warranty on the gene therapy. The therapy is paid for up front by payers (e.g. Medicaid in the US), but if the treatment is then ineffective, the third-party insurance company pays back some of the costs of the therapy to payers. There are, however, still several challenges associated with this approach, such as how ‘ineffective’ is defined and how the warranty premiums are determined, based on the potential effectiveness of the therapy. It also means only those who have healthcare insurance and meet (generally) strict coverage restrictions may be treated, restricting access for some patients. This type of model may not be applicable to most EU member states, and a targeted payment method based on the healthcare system in each member state may be needed.

At WODC, BioMarin described their experiences with Roctavian?, a gene therapy for the treatment of severe haemophilia A. They explained that the therapy had triggered a more rapid uptake from US payers than in the EU, however BioMarin felt EU negotiations offered more flexibility through the opportunity for financial risk sharing opportunities. As gene therapy reimbursement negotiations have typically been complex and lengthy in both Europe and the US, it is important that all stakeholders ensure innovations and improvements to the reimbursement process are made to support timely access for future gene therapies. This is particularly important as gene therapy development moves towards more common conditions and rare conditions for which other treatments are available (to date, licensed gene therapies have tended to focus on conditions with very high unmet need/no treatments available). Given the larger number of patients that may be eligible for gene therapies for more common conditions, payers may struggle to fund these treatments if the costs remain so high. Similarly for conditions with other treatments available, it will be more challenging for gene therapy manufacturers to demonstrate sufficient unmet need to justify high-cost therapies. BioMarin flagged their efforts in proactively educating payers on the value story of Roctavian?, which we agree should be a priority for manufacturers, particularly for diseases where other treatments already exist on the market.

Cost-effectiveness assessments may potentially address these issues, if manufacturers and payers consider the added clinical value of gene therapies against standard of care and then determine a price. However, there will need to be open discussions regarding willingness-to-pay thresholds for these therapies, and considerations on whether manufacturers can viably develop gene therapies for these prices. Ultimately, with many more gene therapies coming to market, it would not be feasible for every product to be associated with high costs. However, as demonstrated in the oncology space, the importance of incremental innovation and improvements should not be underestimated, and therefore market access pathways should not look to discourage this.

Issy, Eleanor, Emma, Juliet and Faye are employees at Costello Medical , which provides scientific support to the healthcare industry in the analysis, interpretation and communication of clinical and health economic data. Due to growing demand across an increasing range of service offerings and geographies, Costello Medical has grown organically since its foundation in 2008 to a team of over 350 based in Cambridge, London, Manchester, Bristol, Boston, Singapore and Shanghai. Alongside our evolving technical and creative capabilities, we remain committed to our core values of high-quality scientific work coupled with exceptional customer service at competitive and transparent prices. For more information on our services, please visit our website. If you would like any further information on the themes presented above, please do not hesitate to contact Isabelle Newell .

[1]European Federation of Pharmaceutical Industries and Associations (EFPIA). Germany, Belgium and France among those hit hardest as Commission’s Pharma-legislation proposals risk Europe losing a third of its share of global R&D by 2040. Available at: Germany, Belgium and France among those hit hardest as Commission’s Pharma-legislation proposals risk Europe losing a third of its share of global R&D by 2040 (efpia.eu)

[2]National Institute for Health and Care Excellence. Interim Process and Methods of the Highly Specialised Technologies Programme Updated to reflect 2017 changes. 2017. Last accessed: 20 November 2023.

[3]Haria K, Choy JY, Kaut J, Griffiths A, Newell I, Whalen JD, Nolthenius J. What is Highly Specialised Technology (HST)? The Revised NICE HST Criteria in Practice. Value in Health. 2023. 26;11: S2.