Orphanisation blog

After leaving Amsterdam before the sun rose, and fresh from speaking the day before at Amsterdam’s World EPA Congress 202, Matthew Hanchard arrived in Brussels just in time for registration at (Re)Act Congress 2025. As the combined hotel and conference venue, the Pullman was conveniently built into Brussels Midi Eurostar station – making the walk very short work! As bi-annual event, the Re(Act) Congress is jointly sponsored by the Blackswan Foundation, International Rare Diseases Research Consortium (IRDiRC) and European Rare Diseases Research Alliance (ERDERA). Jin Ding and I had attended the same congress in Berlin two years ago (Hanchard, 2023), enjoying its mix of clinical researchers, regulators, patient organisations, and policy makers. This time, the smaller size of the event meant all talks remained in one track and a single room, with an ample separate space for posters and breakout areas – Jin Ding presenting her poster in the latter. With few consultancies, and almost no products or services being sold, general discussion felt solution-focused and directed. An evening social event at the Faculty on day 2  providing some light relief. 

On day one, talks covered diagnoses and data. On day two, they turned to novel therapies and advances within the ATMP field (advanced therapy medicinal products), i.e. gene therapies - and on the impact of accessing rare disease treatments for patients everyday lives. On the third and final day, talks turned to pricing, funding models, and the increased uptake of repurposing – taking medicines approved for one condition and then using them for a rare disease instead in place of any specific drug being developed. Across the talks, the recently enacted EU AI Act 2025 and upcoming EU Biotech Act 2025 saw occasional mention, but always as a brief side note. Chris Hendriksz’s (Chief Community Impact Officer at A Rare Cause) provided an insightful history of the shift form newborn genetic screening (as material process of sample gathering to its role with machine learning models as abstracted data. Here, commentors from the audience were keen to note that ERDERA is working hard redress poor choices of endpoints in its mission to offer better diagnoses for undiagnosed individuals with rare diseases. Meanwhile, Marieke Bak (Assistant Professor, Amsterdam UMC / Senior Research Associate at Technical University of Munich) urged more responsible data use in rare disease research, proposing a Ethical, Legal, and Social (ELSI) framework for doing so. On innovations in the field, Nick Sireau (CEO and Chair of Trustees at the AKU Society / Co-founder of both Beacon and Sireau Labs) evidenced the value of advances in messenger ribonucleic acid (mRNA) rare genetic diseases like alkaptonuria (AKU), also known as ‘black bone disease’. Later, Gérald Perret (Programme Director at Genethon) discussed the company’s work to develop an AAV8 vector-delivered microdystrophin gene therapy for Duchenne muscular dystrophy (see also Laugel et al., 2024). Here, highlighting a few talks hardly does justice the sheer quality and depth of presentations; blog posts offer too little space. One standout talk for us though, came from two-time Paralympian Danish national wheelchair rugby player and PhD candidate at Aarhus University, Sofie Skouba. Verging at times close to her work with iHuman’s own Dan Goodley (see Fiis Christensen et al., 2025), Skouba discussed a role for telepresence robotics for children with chronic conditions as a means of alleviating educational exclusion. Skouba covered regulatory hurdles in Nordic countries, and the differing interpretations of mandatory education versus and mandatory schooling – the argument being that educational support, reform, and rethinking are needed. As the day closed, attendees rushed off to prepare for the social event, just a short walk from the venue through various Moroccan and Congolese eateries, greengrocers, and cobbled street.

The final day kicked off at 9.00am sharp with Valentine Nivedita as first speaker (VP Global Product Innovation at Pharmanovia), covering  the company's approach to repurposing and ways of working around regulatory barriers to approval. Next came a talk from Irene Norstedt (Director of the People Directorate at the European Commission) on recent moves to ensure open, equitable, and fairer access to treatment across Europe. Later talks were equally high in calibre, with standout sessions for our project including one by Philip Gribbon (Head of Discovery Research at Fraunhofer ITMP), whose talk included a tentative call for industry to make its non-profitable failed trail results open to others for repurposing. A healthy round of questions saw people like Donald Lo (Director of Preclinical Innovation at NCATS) note that the move could support clinical trials research when it is stuck - stoking innovation. Yet inevitably, talk moved back to data as a core concern for the industry. Comments and suggestions ranged from an argument that IP should be withheld until as late as possible, through to concerns being expressed over the lack of investment for data science infrastructure across Europe, and a need for diligence in data processes for machine learning. More concretely too, on how schemes such as Remidi4All might move towards FAIR data compliance to ensure openness and interoperability ready for machine learning (the latter appearing as a proxy for article intelligence). Elsewhere, commentators like Linda McNamara (WEP Clinical) were quick to highlight that uncritically accepting real-work evidence (RWE) on the bases of real-world data (RWD) is where bias creeps in. Overall, the congress again saw leading experts leave with more questions than answers, and more problems to solve than solutions, all of which supports incremental progress. While our immersion in conferences draws to a close, I have no doubt that the (Re)Act congress 2027 will see repurposing and AI remain key topics, but by then with many successful case examples to demonstrate. 

References

Hanchard, M. (2023) ‘Working towards standardisation and collaboration across rare disease research, iHuman. [Blog}. https://www.sheffield.ac.uk/ihuman/blog/irdirc2023

Hanchard, M., (2025) 'World EPA Congress 2025: The landing of AI and growing appetite for transferable exclusivity', iHuman. [Blog]. https://www.sheffield.ac.uk/ihuman/news/world-epa-congress-2025-landing-ai-and-growing-appetite-transferable-exclusivity

Laugel, V., De Lucia, S., Davion, J., Daniele, D., Cao, F., Sanz, M., Buscara, L., Blaie, S., Thibaut, L., Sagot, M., Riviere, A., Creoff, E., Lelait, M., Valent, A., Perret, G., Braun, A. and Muntoni, F. (2024) ‘410P GNT0004, Genethon's AAV8 vector-delivered microdystrophin gene therapy of Duchenne muscular dystrophy, first data of the phase I/II part of the GNT-016-MDYF all-in-one clinical trial in ambulant boys’, Neuromuscular Disorders, 43(1). doi: 10.1016/j.nmd.2024.07.290.

Friis Christensen, J., Falster, ES., Nino Carreras, B. and Skoubo, S. (2025) 'On the all-inclusive society, or how to leave no one behind – A conversation with Dan Goodley, Yanki Lee, Jos Boys, and Sarah Glerup', Kvinder, Køn & Forskning, 37(2), pp. 12-20. doi: doi: 10.7146/kkf.v37i2.139658.

Matthew Hanchard attended the World Evidence, Pricing, and Access (EPA) Congress 2025 in Amsterdam (going to back-to-back straight on to the IRDiRC congress immediately afterwards. He notes that leaving any field in ethnography can be a tricky task. As Bourdieu notes on the ethnographers’ awkward gaze (Gidley, 2009), you cannot help but take something with you or to leave at least something behind – and you become other to both worlds as a result. As our project progresses from fieldwork (immersion at conferences) to analyses and write-up, reflecting back on the last four years, I have gained a far greater appreciation of the pharmaceutical industry’s inner workings – even publishing a health economics article as a result (Hanchard, 2025). I leave with a position closer to third-way politics than the critical ‘big pharma bad’ I had envisaged upon entry. My new manta: "...but it's more complicated than that". I leave behind a better understanding of what medical sociology can offer industry and policy debates in the hope widening industry thought to be more than periphery footnote or recommendations filler on ‘social factors’. 

Following Terrapin events’ World Orphan Drug and World Evidence Pricing and Access (EPA) Congresses over the last four years began somewhat uneasily. Initially, I was held as outsider and met with scepticism. Two years later, I was invited to speak there. As the fieldwork draws to a close in 2025, the organiser took the time to ask engaging questions about the research progress, understanding the project aims surprisingly well. Throughout the fieldwork, both congresses have changed tack. The World EPA Congress in 2022 saw room sizes in the Dutch modernist central Amsterdam Beurs Van Berlage building become a little too small. Just three years later, it has once again outgrown its space – currently encompassing two giant halls of the glassy-brutalist Amsterdam RAI corporate venue complex in Zuidas (South Amsterdam). The event in 2025 gathered over 1,500 attendees and 300 speakers, with even more likely in 2026! 

Congress topics have shifted over time too. In 2022, post-Covid caution saw a focus on market stability. By the World EPA Congress in 2023 focus had turned to access (in)equity for patients, and the expansion of increasingly niche markets (Hanchard, 2023). It moving on again to sustainability and regulatory change for the World EPA Congress in 2024. The latter, a response in part to an EU-level major overhaul of pharmaceutical policies in 2023. This year, AI took centre-stage. Various businesses offered the latest and greatest in AI, with platforms and tools of all kinds on show, and with surprising niches too. One stall offered virtual reality (VR) headsets to demo their product, an AI analytics informed training tool design to help market access organisations “[e]ngage in scenarios that mimic real-life interactions with healthcare professionals or payers, navigate complex compliance guidelines, and master the art of relationship building and sales strategies within a controlled, engaging virtual environment” (MArS, 2025). Others offered chocolates, coffee, notebooks, and Lego - while many had live demos of AI based products – all licensable for a reasonable fee. At the World EPA Congress in 2021, AI was something to be planned for, an emerging technology on the horizon, something due to arrive sometime soon. By the World EPA Congress in 2025 it has become quite clear that AI has landed firmly in the here and now, with an exciting ecosystem of products emerging. The same sentiment has been noted online by others too – see Bünau‘s (2025) post on LinkedIn for example. Throughout, rather than AI and data becoming platonic buzzwords, event talks fleshed out the contours of our new landscape in detail. That said my account only covers the first day of the congress – with an early morning Eurostar to IRDIRC’s (Re)Act in Brussels seeing me miss talk from the second and third days. 

In terms of talk content, the congress chair Annette Powers (SVP of Global Market Access, Bristol Myers Squibbs) opened with discussion of sustainable access and trends in health economics and outcomes research (HEOR). Four keynotes then set the congress tone: Christoph Glaetzer (Janssen) talked about greater inclusion of patients in market access strategy decisions; Barry Farrimond (ZS) enticingly talked about ‘Transforming market access through Digital, AI, Technology & Analytics'; Chris Mancill (AstraZeneca) examined alliances in ‘Industry commitments and collaborations to health system goals’, turning to data too in a discussion of the ‘trends and opportunities in achieving health equity from the Access to Medicine Index’; Meanwhile, Jayasree Iyer (CEO, Access to Medicines Foundation) provided a focus on global healthcare access inequity. 

Whilst at the event, I flitted between the ‘rare disease’ and ‘reimbursement’ tracks (speaking in the latter). I saw AI being used within clinical trial design, and Girisha Fernando (CEO of Lyfegen) offered a live demo of their ‘drug contracting companion’ pricing simulator.  Taking multiple sclerosis as a case example disease and North Carolina as an example US state, Fernando showed how the tool could quickly suggest an outcomes-based model as the most likely to be successful. In part, Fernando explained,  that was due to that particular federal states’ high number of people covered by Blue cross/Blue shield. As a large language model (LLM) based AI platform, Fernando noted that Lyfegen’s tool ingests real-world data (RWD) from clinical, epidemiological, and financial records alongside public internet records. With a few text-based entries and minor playing around with filters, the tool brought about suggestions in seconds, powered by Open AI GPT 4.0 and Googe Gemini Flash 2.0. Done manually, the same task may have taken a researcher or consultant a few days or even weeks. Meanwhile, others within the Q&A session noted that Anthropic's Claude 2.0 – an LLM often used within health technology Assessment (HTA) might have been another suitable alternative. The question then, was not whether AI was viable – but on which AI is best for each task. And Lyfegen's pricing simulator was far from the only working demo of product at the event. 

Beyond AI, talk of reimbursement was equally as lively. In comparing countries, for example, Tomer Ben Zaken (Director at Astellas) noted that Israel has 100% universal coverage via four healthcare maintenance organisations (Clalit, Maccabi, Leumit, and Meuhedet). Each of which are non-governmental organisations that competitively bid on tenders, creating competition within closed bounds. As a pyramid structure of sorts, Zaken showed $116bn US dollars being allocated as a national budget for healthcare in 2019, with 40% of all national healthcare spends being out-of-pocket (payed by patients or private insurance), giving rise to monopoly markets - with only four state-sanction providers to choose from.  Although, in a structure entirely differ to the EU, UK or USA - treatment price per indication is not permitted in Israel, instead medicines are charged by disease (as a whole) causing various challenges. Using the case of multiple myelopathies, Zaken showed that in 2020 a viable new treatment was rejected (no budget assigned). In 2021 it was rejected again with a focus on first line treatments only. In 2022, it was rejected yet again with a focus on second line treatment instead. Then, in 2023 it was approved, meaning where patients had been accessing the drug as third-line treatment (if two other cheaper and established options had failed), it was now as a first-line treatment despite its far higher cost placing strain on budgets. Access to the ‘recommended’ first-line treatment, then left at mercy of industry and regulators working with the four providers to set a price that would be manageable. Other talks were equally as insightful, and deep too. In my own talk, I restated the three narratives of orphan drug pricing (Hanchard, 2025) and drew on recent interviews to highlight the connection between policy, regulatory gaps, and issues in gaining access to treatment for US patients.  As an example, I noted Charlotte's statement:

“So a hospital might have a clinical trial, and actually the biotech companies are required to pay for the procedures of the clinical trial… [but] if the child gets sick for some other reason, well, they're [already] at the hospital [but] it has to be covered by their insurance….[So] there was a child who was eligible for a clinical trial, but came from a family that only had Medicaid… they did not have private health insurance, [so] the hospital refused to allow them to participate in a clinical trial, because… [their] Medicaid insurance was not as expansive as a private insurance, and which is essentially discrimination against poor people.”

Charlotte, USA

Connecting her statement to policy, and to the US Patient Protection and Affordable Care Act (ACA) 2010 in particular, I demonstrated how access and the actual prices paid by rare disease patients are directly impacted by regulatory changes, with variable inequities brought about as a result - such as some socio-economic groups being excluded from clinical trials on a coverage basis, the  drugs developed being less representative of their target end-users than they perhaps ought to be.

Overall, the congress was positive in tone and celebratory of advances. AI's landing is clearly a boon for many aspects of healthcare, but only if used in the right way. There is a sense that the technology is here, but regulation is yet to catch up. In pricing, there was firm sense too that transferable exclusivity extension vouchers (usually used for to incentivise innovation and investment in antimicrobials) as a purportedly ‘zero-cost’ (offset cost) way to incentivise innovation for the small markets posed by rare disease. No doubt these debates will have continued, but with overlapping conferences to attend, I left in the morning before the congress second day started, catching an early morning Eurostar to Brussels for the (Re)Act conference…   

References

Bünau, P. (2025). ‘Generative AI at the Gate: Impressions from the World EPA Congress 2025’, LinkedIn [Online]. https://www.linkedin.com/pulse/generative-ai-gate-impressions-from-world-epa-2025-paul-von-b%C3%BCnau-gzvmf/.

Gidley, B. (2009). ‘A Note on the Awkwardness of the Ethnographer’. The Sociological Review, 57(3), pp. 526-529. doi: 10.1111/j.1467-954X.2009.01853.x.

Hanchard, M. (2023) ‘The World EPA Congress and shift towards access equity and niche markets’, iHuman. [Blog}. https://www.sheffield.ac.uk/ihuman/blog/world-epa-congress-and-shift-towards-access-equity-and-niche-markets.

Hanchard, M. (2025) ‘Debates over orphan drug pricing: a meta-narrative literature review’. Orphanet: Journal of Rare Disease. 20(107). doi: 10.1186/s13023-025-03634-2.

MArS (2025) Max Insights: The AI-Based Global Market Access Planning Tool [Online]. https://marketaccess4-0.com/ 

Matthew Hanchard published his meta-narrative literature review of orphan drug pricing debates in Orphanet: Journal of Rare Diseases. The article details are as follows:

Title: Debates over orphan drug pricing: a meta-narrative literature review 

Abstact: Rare disease prevalence rates are increasing rapidly worldwide, as are the cost of orphan indication drugs used to treat them, posing significant strain on many healthcare systems. In response, a set of tensions have arisen within academic, activist, advocacy, industry, and policy circles over orphan drug pricing. Yet there has to date been no unifying review of the literature engaging critically with these tensions. Addressing this gap, the article examines the narratives in circulation around orphan pricing, the traditions and epistemic bases they draw on, and their points of contestation/coalescence. It does so through a meta-narrative literature review, finding three core narratives. One involves dispute over outlay costs for developing new orphan drugs, often drawing on normative health economics with a base in practical idealism. It argues that (bio)pharmaceutical manufacturers misuse policy incentives to profit excessively through monopoly capitalism. A second narrative draws on both empirical and normative health economics (often steeped in empiricism paired with a utilitarian standpoint). It contends that high orphan drug prices signify a healthy market and justifiably support longer-term innovation while promoting wider equity of access. A third (midway) narrative draws on the sociology of health and innovation studies alongside normative health economics and health policy studies to suggest alternative models of innovation and valuation. As a unifying meta-narrative, the review finds a sustained call for reform, centred on welfare economics and resource allocation, where current incentives and regulations are held to be insufficient. Overall, the article recommends that regulators look to alternative models of innovation steeped in social science thinking to modify reviewing appraisal, coverage, and reimbursement processes for orphan drugs. Also, that greater patient inclusion and transparency would help include a wider range of intangible social factors that rare disease patients face in accessing high priced orphan drugs.

Citation:
Hanchard, M.S. Debates over orphan drug pricing: a meta-narrative literature review. Orphanet J Rare Dis 20, 107 (2025). https://doi.org/10.1186/s13023-025-03634-2

After being immersed within Terrapin’s World Orphan Drug (Europe and USA) and World Evidence Pricing and Access (EPA) Congresses for the past three years as part the project's ongoing ethnography for the Orphanisation project, Matthew Hanchard has witnessed a narrative and sentiment shift; a move from being an interpretative observer to being accepted by the community as insider. This time, during a Catalonian late autumn, the weather was warm – and missing floods and storms by a mere week – the World Orphan Drug Congress 2024 saw leaders from patient organisations, industry, regulators alike brought together in Fira de Barcelona’s Montjuïc. The venue and networking sites were both set around Poble Espanyol; the famous town village museum built in 1929, under Primo de Rivera’s gaze and looming collapse of Wall Street – a different set of crises. Both venues now host an international mix of business and tourism, inflecting the space with a youthful energy – even if set to play amidst a seemingly stoic noucentist architectural form – in stark contract to the modernism of Amsterdam’s RAI Congress centre or Boston’s Convention Centre (usual venues for the congress). The city has been innovative too, in its shift from tradition to post-industrialism - a former bullfighting ring becomes a shopping centre, a palatial walkway becomes the meeting point for Barcelonistes – seen to collectively chant before their team beat Bayern Munich 4-1. The city also boasts an Alexion development hub, where over 100 staff work less than 3km from the venue for the global biopharmaceutical company (owned by AstraZeneca), making Barcelona a sizeable European loci of expertise in the development of rare disorder therapies.

At the event itself, a first day of workshops set the tone, with Clinigen promoting holistic approaches to drug development that better include patient experiences, while consultancy firm Partners4Access explained how to smoothly navigate drugs through the new EU joint Health Technology Assessment (i.e. EUnetHTA) for approval and market authorisation. Sanofi closed the day with different financing mechanisms for rare disease, and a discussion of Rare Diseases International’s (RDI) call for a World Health Assembly (WHA) resolution on Rare Diseases by 2025 (read more on that here). By evening, a networking session with snacks and open bar (sponsored by AscellaHealth) brought more open discussion and concern, as well as key figures meeting again face-to-face.

The following day, Soraya Bekkali of Alexion (AstraZeneca’s Rare Disease arm) gave opening plenary remarks for the congress proper, with keynote speeches following-on from Virginie Bros-Facer (CEO of EURORDIS), Stelios Kympouropoulos (both a Psychiatrist and MEP for the New Democratic party in Greece), and Elisabetta Zanon (Director of European Policy and Advocacy at Alliance for Regenerative Medicine). Together, their talks sat under the tantalising banner “How will Europe remain competitive in the C> and Rare Disease sector? The role of the research and innovation policies for a stronger pharmaceutical strategy in Europe”. It suggested a softening of definitions between ‘rare’ as a formal disease category and ‘C>’ (less than common) as a broader catch-all monicker.

Slippage in defining terms continued elsewhere too. Some panels remained clearly delineated, like ‘Science and Strategy’, ‘Access and Pricing’, or ‘Real-World Data’, while others saw change. Patient Engagement and Inclusion, for example, became Patient-Centricity. The latter, rather than being a rhetorical ploy or paying lip-service alone saw industry and patient organisation leaders shift narrative - from commercial research choosing how and when to include patients, to instead working with patients as partners able to find means to input on their own terms. Differing interpretations were flagged-up in other contexts too. Nadiah Hanim Abdul Latif (President of the Malaysian Rare Disorders Society), for instance, explained that linguistic nuance and misinformation saw the terms ‘rare’ and ‘disease’ being translated as ‘mutations caused by the covid vaccine’ in many Malay speaking areas – with lower vaccine acceptance as a result. Adding that taking counter-speech and public narratives seriously is important. Words matter.

As a separate concern, in a drug development panel, clinical trails being conducted in China, India, and the Global South were framed as being both a potential point of risk for forms of exploitation, and as a meaningful way to address the rapidly exhausting supply of rare disease patients for clinical trials. Regulatory agencies were urged to work with patient organisation to find new ways of addressing this problematic. In the Real-world data panel, talks equally urged regulatory change. Susanne Michel (VP of Market Access at Clinigen), for instance, discussed the value of using (and allowing strategic use of) Real-World Data (RWD) gathered through managed access programmes within HTA submissions. The argument drew on Polack et al. (2022) to discuss the role of RWE from expanded access programmes (EAPs) in UK NICE health technology assessment (HTA).

Meanwhile, in a regulation focussed panel, Alex Artyomenko (Global Patient Affairs Director of Rare Diseases at Ipsen) presented patient experience maps (PEMs) as a useful approach way to measure patients’ journeys access treatment access. Later talks offered different solutions, Sofie Alverlind (Coordinator and Project Leader at Tandvards och Lakemedelsformansverket [TLV] – the Swedish Dental and Pharmaceuticals Benefit agency) for instance, discussed orphan drug volume and willingness-to-pay criteria, and increasing access at sustainable cost. As a firm adherent of value-based pricing, Alverlind discussed TLVs staircase model – a refined version of UK’s QALY, where reimbursement for high-pried drugs was only to be set for rare diseases with fifty or fewer patients.

Overall, discussion moved again to defining terms – this time with ‘rare’ opened to scrutiny, as a catch-all term for condition with variable levels of prevalence and severity. Beyond the talks, questions asked of speakers struck a similar chord; Daniel O’Connor (Director of Regulatory Policy & Early Access at ABPI, and former Director of Innovation MHRA), for instance, asked probingly of an RWE talk about Clinical Practice Research Datalink - who exactly is expected to pay for the data management costs. At the end of day two, an Alexion-sponsored event with snacks and an open bar at the fabulous Museu Nacional d'Art de Catalunya saw more networking take place, with musings heard over defining terms, the role of RWE, and the likely impact of the US election on Europe.

At the final day of the congress, talks continued along the same tact. That newly redefined terms are needed, and a common set of refined process for regulatory processes are warranted. Some pragmatic concerns were set out too: Anneleine Jonker (Scientific Director of Duchenne Parent Project and Rare disease researchers at the University of Twente), for instance, notes that there has been a great deal of success in developing treatments. In fact, around 500 orphan drugs now available on the market in Europe. However, some have been less successful in practical use than others. As an example, Jonker notes that Spinraza (nusinersen) – an orphan drug for treating spinal muscular atrophy (SMA) is primarily delivered via intrathecal injection using a lumbar puncture - yet around 80% of SMA patients have spinal issues, and so often struggle with a lumbar puncture. Likewise, in lacking care for due process, the EMA – Jonker adds – use a standardised end-point for Duchenne’s muscular dystrophy assessment in the form of a six-minute walk. In the past, this would see various situated practices – such as nurses purposefully telling patients to slow down in order to ‘fail’ the test – making access to treatment more easily obtained, and acceptance for a clinical trail more likely. However, these soft practices, Jonker adds, might begin to wane as we begin to use RWE more often for measuring muscle strength and motor skills.       

Elsewhere, Essex-based Bob Stevens (a trained Sociologist and Group CEO of the MPS Society and Rare Disease Research Partners) who helped co-design the Managed Access agreement (MAA) process and input on NICE Highly Specialised Technologies (HST) pathway used to access high-cost rare disease drugs. As one of the congress neared its close, Stevens noted that clinical trials often fail because the wrong endpoints have been chosen – and are retracted as a result to save costs. Stevens puts forward a new model of funding, where innovation could be incentivised through milestone-based payment by results. Moreover, as a parent to rare disease children, Stevens was highly critical of QALY, adding that it seems unfair to be told as parent on the one hand that we have a rule of rescue, yet on the other that your child’s life is worth a maximum spend of X or Y through a chance of birth. This, for Stevens, is really where patient engagement or involvement falls down in Europe - for lack of a Rare Diseases Task Force dedicated to early access like the FDA have in the USA, laying blame at the feet of regulators. Later, in responding to questions over the ethics of funding sources, and an apparent conflict in taking monies for aiding clinical trials that later result in exceptionally high-prices treatments, Stevens note that that MPS would ‘take money, without out fear or favour, wherever it was appropriate to further treatment development’. Like many other talks, this highlighted a complex set of ephemeral alliances at stake in the rare disease space, at times with contradictory aims.  

In one of the congress' very last closing talks, Toni Roberts (co-Founder of DEBRA South Africa) summarised many of its consistent themes in a talk titled ‘Patients as Partners: Driving change together’ – extolling the value of patients being invited to engage on their own terms, rather than engaged with as medicalised bodies for clinical trials or as sources of evocative testimony for marketable soundbites. Primarily though, Roberts highlighted a growing need for global inequity measures in rare disease medicines access. Paired with concern for regulatory reform and a redefining of terms, Roberts’ talk, and the congress as a whole, both felt as though debates had moved to a more mature platform. Meanwhile, meaningful debate over programmes like EUnetHTA and/or Duchenne UK's Project HERCULES could be overhead in the coffee van queue, with patient organisation leaders being approached by industry leaders for lived, lay, and accumulated expert advice, and regulators move adeptly between groups. Betwixt, the event saw interactions move far beyond blame-shifting over high prices, tokenistic use of patients’ evocative stories for effect, or insular biosocialities forming within indicative areas. Instead, a more productive air filled the space, with a future-facing focus on increasing access to treatment. 

As part of the orphanisation team’s ongoing ethnographic immersion at pharmaceutical and rare disease conferences, Matthew Hanchard attended the US National Organization for Rare Disorders (NORD) ‘Living rare, living stronger’ patient and family forum in Universal City Hilton Hotel, just outside Los Angeles (CA) in mid-June 2024. As a major national event hosted by the largest rare disease umbrella organisation in the world it brought together patients (and family members), patient organisations (POs), and industry from across the USA. It also drew a sizable contingent of nursing staff and genetic counsellors. As such, it provided a great opportunity for networking and helped in recruiting interviewees for a current subproject on ‘the sociotechnical imaginaries of orphan drug access in the USA’ – as USA-based complimentary work to our recently completed work examining ‘patients’ access to orphan drugs in the UK (from patients’ perspectives)’.

The NORD event itself differed from many of those organised by Terrapin, such as the World Orphan Drug Congress or World EPA Congress. Where the latter provide primarily business-facing talks (for industry and POs), the NORD event was far more focussed on patients, giving it more of an informal tone. Attendees swapped corporate attire for event branded T-Shirts, children ran free in dedicated play areas, and talks were interspersed with entertainment like a performance by members of the Rollettes dance troupe. None of that distracted though from the depth or seriousness of discussion; if anything, having patients and family members (the actual people affected) there in the room and interacting as equals rather than medicalised subjects or quantified as data endpoints in graph-form brought a much-needed sense of immediacy and grounded-ness to the fore.  

The talks were clearly split along two parallel tracks. One track focussed on advances in genetic testing and newborn screening, including some of the challenges faced in the USA. For example, Elisa Seeger (Founder of ALD Alliance) noted that while there have been pre-screening tests since the passing of the Newborn Screening Saves Lives Act, and with 37 rare diseases included in Recommended Uniform Screening Panel (RUSP), ‘…in 2019 the RUSP list expired …’. In turn, she adds that by ‘…2024 not one [USA] state is screening for all 37 RUSP conditions’. Here, panel discussion turned to assess the value of opt-in versus mandatory screening models and the resource allocation both entail for national healthcare budgets and payers.

Rather than policy, other speakers turned to discuss wider cultural practices in medicine as normal science and its impact on innovation. Zhanzi (“Mike”) Hu (Co-founder of the new born screening genomics non-profit GUARDIAN) for example, argued that that at present anything outside ‘[clinical mass] spectronomy a no-no from the start..’ for diagnoses, meaning that ‘…we are straggled in the boundaries of our current technologies’.

Meanwhile, the other track focussed on patient experience of living with a rare disease, what it might mean for sexual and reproductive health, and how to find purpose post-diagnosis. A line on thought that resonated with many, including speakers like Amanda Marinoff (Attending Paediatric Oncologist and Clinical Instructor at University of California, San Francisco) who urged the importance of acknowledging parents’ role in “being [their] child’s main advocate [adding that] we learn by having tissues and samples, [which requires that] patients give generously by taking part [in trials and registries]”

The two strands worked well in counterpoint and had clearly been curated with a great deal of care, tact, and experience. The structure was mirrored too in the choice of keynote speakers too, with ‘Under the Lights’ film-maker Miles Levin’s opening talk on community, fulfilment and building future narratives around hope being followed by two policy-focussed panel discussions. One on health equity looked at geography, race, and linguistics to show deep inequities at play with the treatments received by over 30 million rare disease patients across the USA. The other centred on overcoming insurance barriers to access rare disease medicines (including orphan drugs), a topic that members of our team have published on recently (see Hanchard, 2024), with several useful tips for patients to navigate its complexity across differing federal health jurisdictions.

Meanwhile, in looking to the future, Professor Stanley Nelson (Human Genetics and Psychiatry, UCLA) mapped the journey from early-1960s genomic testing through the emergence of a good network with linkages between organisations working on genomics by the 2000s. next, he moved on to protein coding of genomes and exomes in the late-2000s, “capable of finding 85% of all disease-causing mutations” and note that “now RNA [testing] augments routine [clinical] testing” and will likely continue to do so as the main direction of travel.

Curiously, outside the main seminar rooms, the hallway saw stalls set out form a mix of and gene therapies. The followed in the list of sponsors too, with Chiesi an Italian B-Corporation) appearing as Silver sponsor alongside Novartis and the usual west coast ‘big pharma’ companies being listed as Gold sponsors (Amgen, Biogen, Takeda). A small hint, perhaps, of a burgeoning shift towards a mixed-market economy of big players in the rare disease space with greater focus on cell and gene therapies (CGTs) than traditional pharmaceuticals. The latter a topic of another one of our team subprojects, which examines ‘a mixed economy of innovation in drug development for rare diseases’. Interestingly, representatives from CGT manufacturers appeared far more approachable than those from traditional pharmaceutical firms at other conferences too; their stalls staffed by researchers and advocates more than the consultants and/or business development managers encountered at the World Orphan Drug and EPA congresses.

Overall, the event provided a very positive experience, with NORD’s Tiffany and Janus doing a wonderful job of moderating talks and keeping the session on-time and om-rack. It also saw less onus being placed on sales and more on facilitating smaller POs and patient/parents to work together on common goals – primarily gaining earlier diagnoses and raising greater awareness of rarity amongst clinicians, and on brokering access to relevant treatments for US patients. As a closing thought, and much in line with our own work on ‘the social lives of patient stories (SLoPS)‘ project, the key takeaway for patients came from Elisa, who urged people to “tell your story…[because] it is so powerful”.

Jin Ding attended the 2024 Global Rare Disease Research Symposium & Second China Rare Disease Research and Translational Medicine Annual Conference, a collaborative effort by Hope for Rare Foundation, the International Rare Diseases Research Consortium (IRDiRC), and Fudan University. This year's conference, held from May 23-25 in Shanghai, China, brought together over 100 speakers and around 3,000 attendees from global universities, hospitals, academic institutions, patient organizations, and pharmaceutical companies. 

With 20 parallel sessions and several satellite meetings, the event covered a wide range of topics including basic research on rare diseases, gene and cell therapies, Investigator-Initiated Trials (IIT), clinical studies, drug development, and international research collaborations. This symposium highlighted the latest developments and original findings in rare diseases research, especially cell and gene therapies, with a special emphasis on China’s contributions in a global context.

There were many interesting sessions in the panel on international research collaborations. I had the chance to speak at the panel titled "Benefit-sharing: A Thorny Question for Biomedical Innovation," chaired by Dr. Yeyang Su. The session featured speakers who provided valuable insights into various aspects of benefit-sharing in biomedical innovation.

• Dr. Adam Resnick, the director of the Center for Data-Driven Discovery in Biomedicine at Children's Hospital of Philadelphia (CHOP), discussed strategies for establishing a network to facilitate children's brain tumor research.
• Prof. Dong Dong from the Jockey Club School of Public Health and Primary Care at the Chinese University of Hong Kong explored the ethical considerations surrounding care for rare disease patients.
• Prof. Wim Pinxten from Hasselt University provided insights into the ethical considerations on fair pricing and benefit sharing.
• Dr. Linguo Li, who is the director of public policy at the Chinese Organization for Rare Disorders, discussed the evolving role of patient organizations as innovators.
• I delved into the necessity for a new social contract in orphan drug development to achieve equitable returns among stakeholders, transparent pricing, and a sustainable healthcare system.

This conference underscored the importance of collaboration with patient organizations and innovation in advancing rare disease research. Our current project has investigated the growing divergence in orphan drug approvals between the EMA and FDA, highlighting the unequal availability across regions and the significant barrier posed by high prices. This situation is even more dire in middle and low-income countries. Innovation in pharmaceutical R&D is just the first step of the long journal to the patient access. Without innovative business and pricing models, patients cannot access treatments, wasting public resources since early-stage orphan drug R&D is often funded by public grants and patient organizations.

As we look ahead, the insights and connections gained from this symposium will propel our project to further develop the research on a new social contract of orphan drug development to tackle the challenges above. This new social contract will address several key issues:

Global Accessibility: Ensuring that orphan drugs are available in middle and low-income countries, not just in affluent regions.

Fair Pricing: Implementing innovative pricing models that balance affordability for patients and reasonable returns for companies.

Benefit-Sharing: Developing strategies where profits are shared more equitably among stakeholders, including patients, researchers, and pharmaceutical companies.

Public Resource Utilization: Ensuring that the public resources which often supports early-stage orphan drug R&D is effectively utilized by making treatments accessible to all and utilising the returns to address other unmet medical needs, thereby preventing wastage of resources and make the system sustainable.

I extend my sincere gratitude to the conference organizers: Hope for Rare Foundation, International Rare Diseases Research Consortium, Fudan University, and the Chinese Organization for Rare Disorders (CORD). The opportunity to exchange knowledge and insights has been invaluable.

The Orphanisation team spoke at the World's leading pharmaceutical conference on orphan drugs. Matthew Hanchard discussed the value of social media data for diagnosis and Jin Ding covered growing US-EU disparity between drug submissions and approvals.

Having attended several Terrapin events over the last three years as part of our ongoing ethnography of pharmaceutical conferences - speaking at the World Orphan Drug Congress (WODC) in Boston, USA held a slightly different feel. In Europe, we have covered how the World Evidence and Pricing (EPA) Congress in 2022 and 2023 in previous blog posts - both of which held a strong focus on market access, bringing together industry, patient organisations (POs), and regulators. At the WODC, the focus seemed to flow back to market access, but gravitated too towards finding solutions to core issues like the diagnostic odyssey, the pricing wrangle over orphan drugs, regulatory hurdles left to overcome. Discussion felt polemic. The shift in tone followed into the stalls too, where stands like PCMtrails selling at home testing kits for ‘decentralised clinical trials’, jostled with various real-world data and consultancy services of all kinds, through to pre-constituted survey panels, and several PO’s. Yet curiously, unlike the World EPA Congress, there were no biotech and pharma companies there (big, SME, or startup) to set up shop in the lobby. This made it it a little unclear on who exactly the Clinical Research Organisations’ (CROs’) target clients might be! Surely, CROs cannot sell simply to other CROs alone? The conference talks deviated slightly from the World EPA Congress too in their scope of discussion. Rather than a track on ‘Rare Disease’ it held one on ‘Rare Oncology’. Meanwhile, ‘Market Access’ became ‘Global Market Access’, and ‘Big Data and Digital Health’ became ‘AI and Digital Health’ - subtle but notable differences in framing.  The WODC also held a much larger poster session with space for a patient art exhibition, giving attendees time to engage with cutting-edge research, becoming far more of a site for recruitment and headhunting of future staff. 

Stalls - World Orphan Drug Congress - Boston 2024

Exhibition - World Orphan Drug Congress - Boston 2024

Beyond surface appearances, the content of discussion at the event also differed from the World EPA Congress. Over the past three years, the World EPA Congress has moved from a post-pandemic concern for maintaining stability and sustainability in the market through increasing access onto a recent focus on addressing policy wrangles around how to ensure patients gain equitable access to orphan drugs (despite their high price). The WODC somehow felt more solution-focussed, with health economists and activists thrashing out new and novel potential ideas; albeit interspersed with very clear sales pitches for products and services. Within this, some sage perspectives came forward. Championing industry, within a panel worryingly titled ‘Monetising Hope’, Patroski Lawson (CEO of KPM Group DC) noted that “...about 75% of innovation comes from small companies and SMEs…”, likening them to successful family-run restaurants that fail when trying to scale-up, Patrowski added that “....we still need big pharma - they talent scout and offer buy-outs, but how can we get everybody to win?” By contrast, a counterpart panel respondent, Kevin Bagley (former Medicaid Director for the State of Nebraska, now at Strategic Consulting) raised the question that “Medicaid covers around 50% of all [US] births, so who will get less money…[if we increase cover for orphan drugs]?”, referring to an ongoing debate over resource allocation linked to the rule of rescue. Later, Bagley added that “availability is not the same as access - we need all sides to bridge the gap” beckoning collaboration and alliances to improve processes. In short, resolving access issues requires new models and levels of support. On innovation, Bagley went further, boldly stating that “Innovation is at risk! We have gone down a pathway where SMEs push innovation, but then often go out of business. Congress has prioritised innovation but failed to follow through”. Here, a careful juxtaposition between urging more state intervention and stepping back to allow free-market freedoms seemed to be at stake - but with little resolution on its conflicts; if ever a space for social science were to be opened!  

This sentiment followed in part beyond industry too, and into an ‘Advocacy support’ seminar, with patient organisations questioning “whether we are competitors or collaborators…with undue pressure [from] everybody going for the same pot [of money]” (Frank Rivera, President of Stronger Than Sarcoidosis). The latter saw Josie Godfrey (Co-founder and CEO of Realise Advocacy) - a long-standing mainstay speaker at both World EPA and WODC - and key figure for developing rare disease patient organisations, advised that “...having worked with two patient organisations where people [leaders] would not sit in the same room, it is often better to start small, and work slowly“ when building collaborations. Thus, a considered and slow approach to community-building is key. 

Meanwhile, a few speakers looked to pragmatic concerns the industry faces, in the ’Pricing and Reimbursement’ panel for example, Marshall Summar (CEO of Uncommon Cures) noted for instance that the US has only around 120 people able to run and/or conduct rare genetic clinical trials, leaving a large skill gap that brings delay to innovation - there are simply too few physicians to meet industry need. Yet few proposed solutions to many of the issues that industry faces. Elsewhere, as keynote Mark Trusheim (Strategic Director of NEWDIGS, at the Center for Biomedical System Design, Tufts Medical Center) proposed that there should be a “risk-based system where insurers’ licenses could be removed at state level if they fail to provide coverage that has been paid for” - albeit a position at odds with upcoming changes that allow Medicaid coverage for treatments out of state.    

In our own contributions, our team presented research on the value of social media data for diagnosis (Matthew Hanchard) in the ‘Diagnosis’ panel and a comparison of EU and US orphan drug submissions versus approvals and authorisations (Jin Ding). As a result, we remained largely tied to our respective panels as attendees. But within each panel, and others that we delved into, Jin and I felt that the event and much of its discussion was framed by rapidly shifting policy amidst the run-up to the next US Presidential election, but still firmly steeped in a normative understanding of policy. As such, our presentations - coming from a social science origin - required that we initially justify social science and the value of theory before making our case. As academics, this led us to address a different set of ‘So What..?’ questions; less on what can this tell us, or why is this significant, and more instead on how does this improve either profit margin or equitable access to healthcare. It will certainly be interesting to trace these debates as they evolve through further conferences in the run-up to the US presidential election, and in the same year as the UK general election and many others across the EU. 

by Eva Hilberg and Aleksandra Stelmach

NIC (2020) ''. Available at: https://unsplash.com/photos/gray-laboratory-machine-to8o0bqOA6Q under a CC-BY license.

Gene therapies are undoubtedly the pharmaceutical hot topic of the moment. As the first genuinely revolutionary treatments such as Zolgensma and Libmeldy are slowly being integrated into regular care in several countries, the industry seems to have at last arrived at the often-discussed underlying step-change in the nature of medical treatment, moving to personalised modifications on the molecular level. Gene therapies are cutting-edge techniques that modify “a person’s gene to treat or cure disease” by replacing certain genes with their healthy copies, by inactivating them or by introducing “a new or modified gene into the body to help treat a disease” (FDA 2018). For decades dubbed as the treatments of the future, gene therapies are becoming, as some argue, the treatments of the present, transforming the ways in which diseases, especially rare diseases could be managed and even cured (Finkel 2019). Media reports have turned this new development into “miracle cures” (Fay Cortez 2019) promising to treat incurable and rare genetic disorders, giving hope to patients and their families. As more gene therapies are being approved by regulators – in the US for example, the Food and Drug Administration (2023) has so far approved about 30 such novel treatments – the stakes for such types of speculation are increasing, as is the price for each gene treatment (Zolgensma currently has a list price of 1.795 million pounds per dose).

In this context, future visions clearly operate as more than just potentially hyperbolic statements. Instead these (often officially generated) expectations are collectively produced and circulated between actors and within innovation and policy spaces, and they sustain specific agendas and shape policy making (Van Lente 2012). Rather than being mere descriptions of events, expectations have a mobilising and performative function that seek to bring about specific changes to the current situation by emphasising hopes and opportunities rather than challenges and obstacles. In the context of pharmaceutical development, these expectations can also motivate future investment and garner attention for research that is still underway – these types of expectations have in the past been highly pivotal in the development of the modern biotech sector (Cooper 2008). At first glance, the case of gene therapy seems to bring together both the best that research can deliver, and the worst in terms of excess expectation raised on the back of these new developments. We argue that the ways in which futures are at work here can bring about a better understanding of both the way in which pharmaceutical development operates in the post-genomic era, and also how different actors may be positioning themselves at the emergence of a new paradigm of treatment.

A collaborative research project explored these (and other) questions over the past year by beginning to map the promises made and expectations raised during this transition to the future of medical treatment. A team of researchers including Eva Hilberg, Aleksandra Stelmach, Tineke Kleinhout-Vliek, and Paul Martin at the University of Sheffield and the University of Utrecht worked together on developing an approach to analysing this emerging vision of the future of medical treatment, and also held an inaugural stakeholder workshop that engaged with the meaning of future narratives for the regulation of new pharmaceuticals. The event mapped different regulatory futures in practical detail, and also began to open the debate to explore a potential for different types of participation, such as NGOs and also government representatives. Overall, it became clear that how the future is envisaged depends largely on who imagines it, and what images and words are used to describe future developments.

These images and words will be studied more closely in the next stages of the project, thus continuing the study of a new field of medical intervention at the moment in which imagination becomes reality. There are of course still numerous challenges to the development of gene therapies, including extremely high prices of treatments that risk undermining the ‘gene therapy revolution’ (Editorial 2023) and making it unavailable to patients, especially those from disadvantaged sections of society and from the Global South. The counter-imaginaries already paint the visions of gene therapies as the preserve of the wealthy rather than a cure for the masses (Editorial 2021). The futures of gene therapies as envisioned by patients and their families could also differ significantly from those imagined by companies (see previous blog posts by Jin Ding  and Eva Hilberg and Tineke Kleinhout-Vliek). Other key issues remain, such as if gene therapies will work and for how long, and what type of legislation would be needed to make them accessible (Reardon 2023). But the emergence of gene therapy still marks a unique moment of (potential) paradigmatic revolution that could re-set our imagination of future medical treatment for decades to come.
 

References

Cooper M (2008) Life as surplus: biotechnology and capitalism in the neoliberal era (Seattle: University of Washington Press)

Editorial (2021) Gene therapies should be for all. Nature Medicine, 27 131, https://doi.org/10.1038/s41591-021-01481-9

Editorial (2023). The gene-therapy revolution risks stalling if we don’t talk about drug pricing. Nature 616, 629-630. Doi: https://doi.org/10.1038/d41586-023-01389-z

Fay Cortez M (2019) Welcome to the Age of One-Shot Miracle Cures That Can Cost Millions’, Bloomberg UK,  June 1 available at: https://www.bloomberg.com/news/features/2019-06-05/gene-therapy-appears-to-be-beating-once-incurable-diseases?in_source=embedded-checkout-banner

Finkel E (2019). The gene therapy revolution is here. Medicine is scrambling to keep pace. The Conversation  June 5. Available at:  https://theconversation.com/the-gene-therapy-revolution-is-here-medicine-is-scrambling-to-keep-pace-118329

Food and Drug Administration [FDA} (2018) What is Gene Therapy?. July 25. Available at: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy

Food and Drug Administration [FDA] (2023) Approved Cellular and Gene Therapy Products, June 30. Available at: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products

Reardon S (2023). ‘It’s a vote for hope’: first gene therapy for muscular dystrophy nears approval, but will it work?, Nature 618, 451-453. doi: https://doi.org/10.1038/d41586-023-01799-z
Van Lente, H. (2012). Navigating foresight in a sea of expectations: lessons from the sociology of expectations. Technology analysis & strategic management, 24(8), 769-782.

Eva Hilberg, PhD
Tineke Kleinhout-Vliek, PhD
21-Jun-2022

It looks as though stories are everywhere nowadays. Within qualitative research, there is an increased recognition of the relative power of stories, because we relate to people experiencing things in a different way than we relate to numbers. Stories have a strong affective dimension: you ‘experience’ a story with the person telling it, engaging your emotions as well as your brain. We are also far more likely to remember data in the form of a story. To make sense of our lives, we all engage in story-telling, whether on Instagram or down the pub: about ourselves, our experiences, the people we meet and the things we do. These are, of course, not entirely fictional accounts, but a conscious selection of all the many and muddled ‘data points’ of life, often with a narrative arc with a clear beginning and an end, and more often than not organized around a problem that is overcome somewhere along the way.

Patients are no different in this, as Arthur Frank so memorably pointed out in the seminal Wounded Storyteller (2^nd ed., 2013). Nowadays many patients blog, vlog or even write books to share their diagnostic and treatment journeys with others. They may also get invited to tell their stories at conferences hosted by pharmaceutical companies, or to contribute ‘lived experience’ to deliberations on a reimbursement decision on a medicine targeting their illness. From the very first encounter, usually when they first go to their general practitioner, they begin to share their story in a great number of places (Van de Bovenkamp et al., 2020). This is especially the case for rare disease patients, as theirs is often a long road to diagnosis, followed by difficulties in accessing treatment. Along the way, a great many stories then become public property, evoking a strong response from society. One example is baby Jayme, a Spinal Muscular Atrophy patient who, through crowdfunding, got access to treatment with Zolgensma in Hungary, nearly 1,500 km from his home in Rijswijk, the Netherlands (RTL nieuws, 2020).

The increasing focus on patient engagement and involvement also comes from the policy side, with a steadily growing interest in qualitative data. Patients’ experiential expertise and knowledge are now arguably more valued than they used to be. At the same time, policy makers and regulators are not well-equipped to deal with these more heterogeneous types of information. It is difficult to weigh a patient’s lived experience and personal responses against an incremental cost-effectiveness ratio, which seeks to capture the lived experience of many patients, yet at the same time reduces these to numbers (Mills & Hilberg, 2019) – especially when faced with that particular patient in the decision-making setting (Kleinhout-Vliek et al., 2021). 

With so much official emphasis on qualitative experiential data, it is worth bearing in mind that sociology tells us that the setting shapes the input (see for instance overview in Petrakaki et al 2018). Stories are highly contextual, as where you are and whom you meet influences the story you tell, and the result will be interpreted in different ways by each audience. These acts of adjustment and reception occur both on a conscious and subconscious level, all of the time, throughout our lives. This does not mean that the content is less ‘true’ as a result, it only seeks to point out the interpersonal dynamics that go into the representation of individual experience, which can be due to the creation of different expectations, such as for instance those in a diagnostic encounter compared to an official ‘conference’ setting labelled ‘patient experience’, or a contribution to a board deciding on market access to medicines. The question is, how are patients’ stories shaped by their setting? What considerations affect this process, which stories are apparently ‘allowed’ and which not, how are these stories valued (in research and in policy), and what effect may this have on decision-making? In an interdisciplinary strand of research developed in collaboration with Erasmus University Rotterdam, we seek to better understand these matters through observations and key interviews. This matters as it helps us to better conceptualise how social pharmaceutical innovation initiatives are influenced by and shared across a relatively wide variety of settings.

References

Frank, A.W. (2013). The Wounded Storyteller : Body, Illness, and Ethics. Second ed. Chicago, Illinois ; London.

Kleinhout-Vliek, T., De Bont, A., & Boer, B. (2021). Necessity under construction–societal weighing rationality in the appraisal of health care technologies. Health Economics, Policy and Law, 16(4), 457-472.

Mills, C. and Hilberg, E. (2019), ‘Built for expansion’: the ‘social life’ of the WHO's mental health GAP Intervention Guide. Sociol Health Illn, 41: 162-175. https://doi.org/10.1111/1467-9566.12870

Petrakaki, D., E. Hilberg & J. Waring (2018), ‘Between empowerment and self-discipline: Governing patients' conduct through technological self-care’, in: Social Science and Medicine, Vol. 213, September 2018, pp. 146-153. DOI: https://doi.org/10.1016/j.socscimed.2018.07.043

van de Bovenkamp, H. M., Platenkamp, C., & Bal, R. (2020). Understanding patient experiences: The powerful source of written patient stories. Health Expectations: an international journal of public participation in health care and health policy, 23(3), 717.

RTL nieuws (2020). Hoe is het met baby Jayme? 'We hoeven geen afscheid te nemen'. Accessed on 16 June 2022 via https://www.rtlnieuws.nl/nieuws/nederland/artikel/5198170/baby-jayme-spierziekte-sma-behandeling-zolgensma-hongarije

Jin Ding, PhD
20-Aug-2022

What are Orphan Medical Products (OMPs)?

Orphan medical products (OMPs) are used for the diagnosis, prevention or treatment of rare disease, which is defined as a condition affecting fewer than 5 in 10,000 people. Rare diseases can have a severe impact on the quality of life for patients. To date, over 7000 rare diseases have been identified globally, but most of these are without effective treatment. The main factor in this treatment gap for rare diseases is the limited profitability of niche treatments, making it very difficult for  pharmaceutical companies to recoup the high costs of drug research and development (R&D) for such small markets.

To better address the unmet medical needs of rare disease patients, regulations have been passed in a number of countries to incentivize the development of OMPs. The US was the first country to pass a dedicated Orphan Drug Act (ODA) in 1983. The  EU introduced legislation in 2000, and in 2000 the UK outlined the rules on the application and incentives of OMPs. From 2021, the UK will take over its own national responsibility for products previously governed by EU legislation. Major incentives for stimulating OMPs development include: 7-year market exclusivity, tax credit, fee waiver, research grant and regulatory assistance. On the face of it, these incentives have been a success, as the number of approved orphan drugs has increased since their implementations. To qualify for the incentives, sponsors must submit an application for orphan drug designation to the regulatory agency, for example, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. 

In the UK, in order to qualify in terms of the criteria of orphan designation for a rare condition, a medical product must meet the following criteria:

• It must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating
• The prevalence of the condition in Great Britain must not be more than 5 in 10,000, or it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development
• No satisfactory method of diagnosis, prevention or treatment of the condition concerned exists in Great Britain, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition

But it is important to note that not all products used for the diagnosis, prevention, or treatment of rare diseases are OMPs, only medical products authorised by regulatory agencies with an orphan designation can be categorised as OMPs. All orphan registered products and expired orphan registered products are published on the MHRA website.

Our project

How orphan drug R&D operates in actual practice is far from straightforward. According to our ongoing research as part of a wider analysis of the orphanisation, since the enactment of orphan drug legislation in the EU in 2000 till 2020 (before Brexit), the number of approved OMPs in the EU was only a small fraction of the number of approved OMPs in the US. The gap between the EU and US has been growing since 2010. Once these OMPs have been centrally authorised in the EU, they are assessed on pricing and reimbursement at an individual  EU member state (national) level before the drug is made available to patients. The actual accessibility of OMPs varies significantly among EU member states, and in the UK,  not all EU-authorized OMPs are in fact recommended by the national health technology assessment agency NICE(The National Institute for Health and Care Excellence). There is also a considerable time delay (27.6 months) between EU authorization and NICE reimbursement decision (see Figure 1). 

Figure 1. Comparison of access to OMPs - (from Zomora et al., 2019)

Previous studies about orphan drug accessibility have focused on market access and reimbursement, but they have not taken the perspective of patients into account. Our current project emphasises patients’ involvement as active and equal participants in this process, seeking to provide an alternative to traditional research approaches in the areas of health economics, health policy, and social sciences.

To recognize the experience, needs, and preferences of rare disease patients without treatments, this participatory research project seeks to answer the following questions:  

• Identifying problems: What’s the position of UK orphan drug accessibility among the US and major EU countries?
• Assessing impact: What are the implications of inaccessibility for rare diseases patients?
• Informing policy: What are the roadblocks that need to be addressed to improve patient access?

Funding and Acknowledgements

This study is commissioned and funded by Research England.

The first step of this project is to identify the real-life accessibility of orphan drugs, contrasting inaccessibility in one geographical context with those that are available in other countries. Our findings will later be supplemented by further research in order to investigate the impact of the lack of treatments on patients’ lives. This project is a first step towards this larger analysis, starting with an online survey that will be sent to the UK rare disease patients/patient organisations in October 2022. 

We are very keen  to work closely with rare disease patient organisations, and look forward to developing long-term collaborative community partnership with UK rare disease patients/patient organisations. If you are interested in this project, would like to take part, or have any questions, please contact us at: orphanisation@sheffield.ac.uk.

Our team
 

References

Zamora, B., Maignen, F., O’Neill, P. Mestre-Ferrandiz, J., and Garau, M. (2019) 'Comparing access to orphan medicinal products in Europe'. Orphanet Journal of Rare Diseases. 14(95), pp. 2-12. https://doi.org/10.1186/s13023-019-1078-5