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 par our ongoing ethnography for the Orphanisation project, I have witnessed a narrative and sentiment shift; I too have moved 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.
