Press Release
Épalinges, Switzerland, June 15th, 2026
Cross-industry white paper calls for three paradigm shifts to unlock orphan drug development
“Drive For Change,” authored by leaders from Volv Global, Sanofi, Fondation Ipsen, Unitechpharma, and brave2change, sets out a strategic roadmap to overcome the systemic barriers holding back rare disease drug development.
In brief
- Approximately 95% of identified rare diseases have no approved treatment, with an economic burden estimated at nearly $1 trillion annually in the United States alone; Drive For Change proposes concrete paradigm shifts to address the root causes of this gap.
- The white paper identifies inaccurate population size estimates, incomplete understanding of rare disease biology, and narrow cost-burden frameworks as the three fundamental barriers to orphan drug development, and recommends specific, actionable remedies for each.
- Advanced machine learning applied to real-world patient data is identified as a critical enabling technology – capable of uncovering undiagnosed patient populations many times larger than current estimates, directly improving trial feasibility and commercial viability for pharmaceutical sponsors.
Volv Global today publishes Drive For Change: Paradigm Shifts and Strategic Recommendations to Overcome Barriers in Orphan Drug Development, a white paper authored in collaboration with senior leaders from pharma, Sanofi, Fondation Ipsen, Unitechpharma, and patient advocacy, brave2change. The paper is grounded in workshops and surveys conducted at the World Orphan Drug Congress in 2023, spanning 25 countries and drawing on the perspectives of both industry professionals and patient representatives.
Despite regulatory incentives on both sides of the Atlantic, approximately 95% of the more than 10,000 identified rare diseases still have no approved treatment. Around 400 million people worldwide are affected. The diagnostic journey for rare disease patients averages close to five years, and delayed diagnosis carries a documented economic cost of up to $517,000 per patient in avoidable expenditure in the United States. At the same time, several major pharmaceutical companies have recently scaled back or withdrawn from rare disease programmes, citing high costs, scientific complexity, and uncertain returns. The pressure on the sector is intensifying at precisely the moment when patients most need it to advance.
Drive For Change argues that the underlying barriers are neither inevitable nor intractable. Three structural paradigms, the authors contend, must be challenged simultaneously: how patient populations are estimated, how rare disease biology is understood, and how the true cost and burden of disease is evaluated. On population size, the paper documents a profound gap between what practitioners believe is necessary – knowing the true prevalence of a disease – and what they believe is achievable. On disease biology, it charts the consequences of pipeline herding, where resources concentrate in well-understood indications whilst ultra-rare diseases remain largely unaddressed. On cost and burden, it demonstrates that current health technology assessment frameworks systematically undercount indirect costs, misdiagnosis expenditure, and productivity losses, resulting in orphan drugs being undervalued relative to their genuine societal impact.
Volv Global’s contribution to the paper spans both conceptual framing and evidence of what is now achievable. The paper presents case study data illustrating that Volv Global’s inTrigue methodology identified approximately 3.2 times the predicted patient count for a neuroendocrine tumour indication compared with the sponsor’s prior epidemiological estimate, and that a prospective pilot deployment for Fabry and Pompe disease in a UK primary care setting produced a 50% to 100% increase in diagnosis rates over a period during which diagnosis rates had been unchanged for ten years. These results demonstrate that AI-driven patient-finding, applied to real-world data at population scale, can materially shift what pharmaceutical sponsors understand about addressable markets – and therefore about the investment case for orphan drug development.
The white paper reflects deliberate cross-sector authorship. Kristina An Haack, Senior Global Project Head at Sanofi and Head of Clinical Development for Inherited Neurometabolic Diseases, brings three decades of orphan drug development experience across preclinical through late-stage programmes. Professor James A. Levine, President of Fondation Ipsen, draws on thirty years of physician-scientist experience and a track record spanning more than thirty-five companies. Dr Mahdi Farhan of Unitechpharma contributes extensive expertise in drug development across biologics and small molecules, including rare diseases such as Usher syndrome. Bernd Rosenbichler, founder of brave2change and parent of a child with Alström syndrome, provides the patient and caregiver perspective that anchors the entire paper’s argument in lived experience.
From the authors
“Throughout my career in clinical development, I have seen the same barriers slow the progress of novel treatments – and time and again, the root cause is the same: as an industry, we do not adequately understand the lived clinical experience of patients, both before and after diagnosis. Today, we have more tools to do exactly that than ever before. Drive For Change is a call to use them.” – Léon van Wouwe, Clinical Innovation Director, Volv Global, Lead Author
“Rare disease drug development is stuck in a self-fulfilling loop: small estimated populations, fragile business cases, programmes shelved before they reach patients. Drive For Change names the loop – and shows that with real-world data and modern AI, the addressable population is almost always larger than the sponsor believed. That is what shifts the investment case, and that is what gets treatments to patients.” – Christopher Rudolf, CEO & Founder, Volv Global
“I am motivated to find and develop a treatment that makes a difference in the lives of Usher 3 patients. Every day without treatment their world becomes darker and more silent – as the loss of their most precious senses, vision, and hearing, continues. I’m inspired by these amazing individuals as they try to lead an independent life despite all the challenges.” – Mahdi Farhan, Unitechpharma SA
“I watched how an undiagnosed rare disease destroyed the life of my father’s beloved wife. There is no diagnosis. No cure exists. My three decades of experience as a physician-scientist supporting 37 new companies came to the fore; I can help – so can you.” – Professor James A. Levine, President, Fondation Ipsen
“My son Ben’s admirably positive mindset and his passion for art are what inspire me to drive for change in orphan drug development. He has been diagnosed with Alström syndrome. Watching him progressively lose his eyesight and hearing is the most difficult thing I had to face in my entire life.” – Bernd Rosenbichler, Founder, brave2change
“Listening to patients, families and advocacy groups describe their search for help, and recognising how many diseases still have no treatment at all, changed how I see my work. I look forward to the day when, by applying data and AI to accelerate the right treatments to the right patients, we can reach as many of these families as possible.” – Dr Vahid Esmaeili, Data Science & Digital Health Director, Volv Global
Note to editors
Drive For Change is based on workshops and surveys conducted at the World Orphan Drug Congress USA 2023 (Washington DC) and the World Orphan Drug Congress Europe 2023 (Sitges, Spain), supplemented by a comprehensive review of current literature. Approximately two-thirds of workshop participants were industry professionals, drawn from 25 countries. Case study data referenced in the paper relating to patient identification uses Volv Global’s proprietary machine learning methodology applied to real-world patient data. The neuroendocrine tumour finding and the Fabry/Pompe primary care pilot results are drawn from Volv Global’s production-deployed collaborations with pharmaceutical partners; full methodological detail is available in the white paper itself. The paper is available to download at www.volv.global.
About the contributing authors
Léon van Wouwe, Clinical Innovation Director, Volv Global (Lead Author). Léon has over 20 years of experience in pharmaceutical and health technology companies across global, regional and local clinical development roles. He holds an MSc in Biology (Medical Biology) from Leiden University and has worked across the UK, Germany, Switzerland and the Netherlands.
Dr Kristina An Haack, MD, Senior Global Project Head, Sanofi. A paediatric physician scientist specialising in inherited metabolic disorders, with a focus on neurometabolic orphan diseases, Dr An Haack has been involved in several successful orphan drug approvals across 30 years spanning academia, research and drug development. She is also Medical Leader of Sanofi’s Paediatric Medicines Network and active in several IHI public-private collaborations.
Dr Mahdi Farhan, Unitechpharma SA. Dr Farhan is a physician and surgeon (MB, ChB, FRCS) with over 18 years of medical experience spanning cardiac and general surgery, and extensive drug development expertise across biologics and small molecules in oncology, immunology, infectious diseases and rare conditions including Usher syndrome and Pulmonary Arterial Hypertension. He has held senior roles at Roche, Novimmune and Debiopharm, and is currently overseeing Phase 1 development of a novel therapy for Usher Syndrome Type 3.
Professor James A. Levine, MD PhD, President, Fondation Ipsen. A physician, scientist and entrepreneur, James has published more than 200 peer-reviewed articles, including papers in Science, Nature, the New England Journal of Medicine, The Lancet and JAMA. He has been awarded more than 100 patents, helped found 35 companies, and has consulted to the Office of the President of the United States. He received the President’s Medal for promoting social embeddedness in 2018.
Bernd Rosenbichler, Founder, brave2change. After more than 23 years in the automotive industry, Bernd left his career to advocate for people living with Alström syndrome, the rare disease his son Ben lives with. He has built a patient organisation, launched public campaigns and re-vitalised international advocacy networks, drawing on business and personal experience across Austria, the US, Germany, Dubai and China.
Dr Vahid Esmaeili, Data Science & Digital Health Director, Volv Global. Dr Esmaeili holds an MSc in Biomedical Engineering and a PhD in Neuroscience, with expertise spanning medical devices, neuroscience and AI-driven healthcare applications. He leads Volv Global’s data science function, translating complex clinical challenges into machine learning solutions at population scale.
Christopher Rudolf, CEO & Founder, Volv Global. Christopher is a technology entrepreneur and business advisor with over 30 years of experience in data science, AI and medical informatics. He leads Volv Global’s mission to accelerate diagnosis and improve outcomes for people with rare and difficult-to-diagnose diseases. He is a visiting professor at EPFL and UNIL.
Links
About Volv Global
Volv Global is a healthcare AI company founded in 2017 and headquartered in Épalinges, Switzerland. Its mission is to generate new knowledge at speed, close the diagnostic gap, as well as other gaps in the care pathway, to improve patient outcomes. Volv Global works across conditions where patients are difficult to identify, where the window for effective treatment is narrow, and where understanding which patients will progress or need therapy beyond standard care can meaningfully change outcomes. It is a trusted partner to leading pharmaceutical organisations across the USA and Europe, with capabilities deployed in live clinical programmes.
Applying a proprietary machine learning methodology to population-scale real-world data – accessed through trusted data partners covering more than 400 million patients – Volv Global generates disease intelligence that enables pharmaceutical teams to de-risk clinical programmes, identify and stratify patient populations with greater precision, and build stronger real-world evidence. For clinicians, Volv Global’s insights are designed to surface actionable signals within existing care pathways. For patients, they translate into earlier diagnosis, better-informed treatment decisions, and a faster path through a diagnostic system that too often leaves difficult-to-diagnose diseases unrecognised for years.
Volv Global’s solutions each address a distinct clinical question across the patient journey, and are configured to the client’s specific research question, disease area, and healthcare setting. Volv Global does not hold patient data; all work is conducted within the governed environments operating under applicable privacy and regulatory frameworks.
Key Questions About Drive For Change
Why has orphan drug development stalled, when the unmet need is so clear?
The unmet need is enormous and well documented. What the paper addresses is why that need alone has not been sufficient to drive investment at scale. The answer lies in three compounding problems that together make orphan drug development look riskier than it is. Patient populations appear too small to justify the investment – but this is largely because the undiagnosed population is invisible to conventional methods. Disease biology is poorly understood in many indications because pipeline herding has concentrated research effort in a small number of already well-characterised diseases. And the economic case for treatment is consistently underestimated because HTA frameworks were not designed to capture the full burden of rare disease. The paper addresses each of these in turn, with evidence that each is solvable.
What is the evidence that patient populations are being undercounted?
The paper presents two specific results from Volv Global’s deployed work. In one case, Volv Global’s inTrigue methodology flagged approximately 3.2 times the predicted patient count for a neuroendocrine tumour indication compared with the sponsor’s prior estimate. In another, a prospective pilot for Fabry and Pompe disease in a UK primary care setting produced a 50% to 100% increase in diagnosis rates in a disease area where rates had been static for ten years. These are production-deployed results, not modelling exercises. The implication for any sponsor making investment decisions based on conventional epidemiological estimates is significant: the true addressable population may be substantially larger than the current figures suggest.
What does the paper recommend on disease biology and natural history?
The paper argues that real-world patient data, rigorously collected and analysed through modern machine learning, can serve as the foundation for a new generation of natural history studies. Unlike the traditional approach – manually interrogating small patient records sets within a clinical setting – AI-driven natural history studies can learn from millions of anonymised longitudinal patient journeys at population scale, capturing early signals, mapping disease heterogeneity, and identifying patient subgroups that conventional methods miss entirely. This matters because a richer understanding of natural history is precisely what pharmaceutical sponsors need to de-risk early development decisions in less well-understood disease areas.
How does the paper propose to reform cost and burden assessment?
The paper makes the case that current valuation models capture only a fraction of what rare disease actually costs – to patients, caregivers, healthcare systems, and the economy. Indirect costs, misdiagnosis expenditure, repeated unnecessary consultations, lost productivity, and the value unlocked by earlier diagnosis are routinely excluded or underweighted. From 2028, all rare disease HTAs in Europe will depend on a single Joint Clinical Assessment, raising the evidence bar further. The paper proposes expanding HTA frameworks to include these broader dimensions, and linking reimbursement directly to demonstrated real-world clinical outcomes – an approach that requires coordinated collaboration between pharmaceutical companies, payers, regulatory authorities, and patients, but that the authors argue is both necessary and achievable.
Who are the contributing authors and why does the cross-sector authorship matter?
The paper brings together a paediatric physician scientist with thirty years of orphan drug development experience at Sanofi; a physician-scientist and entrepreneur who has helped found thirty-five companies and published in Nature, The Lancet and the New England Journal of Medicine; a physician and drug developer overseeing Phase 1 development of a novel therapy for Usher Syndrome Type 3; a parent and caregiver advocate whose son lives with Alström syndrome; and the clinical innovation and data science team at Volv Global. The cross-sector authorship is deliberate. The barriers to orphan drug development are not owned by any single function or stakeholder group – and neither are the solutions. A paper that speaks only from within industry, or only from patient advocacy, or only from data science, would address only part of the problem. Drive For Change is an attempt to hold all of it at once.
Where can I download the paper?
You can download it here.
For more information, please contact:
Le Vin Chin
Marketing & Communications Director
[email protected]
Volv Global SA
Route de la Corniche 3B, 1066 Épalinges, Switzerland
