White paper urges three shifts to speed orphan drug development

Volv Global and industry leaders published a white paper Tuesday calling for three paradigm shifts to overcome the biggest barriers to orphan drug development. The report argues that better prevalence estimates, deeper disease biology insight and broader cost frameworks could unlock treatments for millions of rare disease patients worldwide.

Why it matters: - Approximately 95% of the more than 10,000 identified rare diseases still have no approved treatment. - Around 400 million people worldwide are affected by rare diseases. - Delayed diagnosis can take close to five years and carry up to $517,000 per patient in avoidable U.S. spending. - The rare disease gap remains costly for health systems and leaves many patients without options despite regulatory incentives in the U.S. and Europe.

What happened: - Volv Global published Drive For Change: Paradigm Shifts and Strategic Recommendations to Overcome Barriers in Orphan Drug Development on June 15, 2026. - The white paper was developed with senior leaders from Sanofi, Fondation Ipsen, Unitechpharma and patient advocacy group brave2change. - The paper draws on workshops and surveys from the World Orphan Drug Congress in 2023. - The research spans 25 countries and incorporates views from industry professionals and patient representatives.

The details: - The white paper identifies three fundamental barriers: inaccurate population size estimates, incomplete understanding of rare disease biology and narrow cost-burden frameworks. - The authors recommend specific remedies for each barrier and frame the problem as structural rather than inevitable. - On prevalence, the paper says drug developers often cannot bridge the gap between knowing a disease’s true prevalence matters and what they can practically measure today. - On biology, the paper says pipeline herding pushes resources toward better-known indications while ultra-rare diseases remain underfunded. - On cost, the paper says current health technology assessment frameworks miss indirect costs, misdiagnosis expenses and productivity losses, which can undervalue orphan drugs. - The paper argues that advanced machine learning applied to real-world patient data could uncover undiagnosed populations many times larger than current estimates. - Volv Global says that shift would improve trial feasibility and commercial viability for pharma sponsors.

Between the lines: - The report is not just making a policy case. It is making an investment case for orphan drug development. - The core argument is that many orphan programs look too small or too risky because the patient base has been mismeasured. - The paper positions AI-driven patient finding as a way to expand addressable markets, which could change how sponsors judge whether to start or continue rare disease programs. - The authorship mixes pharma, clinical development, disease expertise and patient experience, which strengthens the paper’s credibility across stakeholder groups. - Volv Global’s examples are meant to show the shift is already possible, not only theoretical.

The details: - In one case study, Volv Global’s inTrigue methodology identified about 3.2 times the predicted patient count for a neuroendocrine tumour indication versus the sponsor’s prior epidemiological estimate. - In a prospective pilot for Fabry and Pompe disease in a U.K. primary care setting, diagnosis rates rose 50% to 100% after being unchanged for 10 years. - The paper says those results show AI-driven patient finding at population scale can materially alter how sponsors view addressable markets.

Who wrote it: - Kristina An Haack of Sanofi brought three decades of orphan drug development experience across preclinical through late-stage programs. - Professor James A. Levine of Fondation Ipsen contributed physician-scientist experience spanning more than 35 companies. - Dr. Mahdi Farhan of Unitechpharma contributed drug development expertise across biologics and small molecules, including rare diseases such as Usher syndrome. - Bernd Rosenbichler of brave2change added the patient and caregiver perspective as the parent of a child with Alström syndrome.

From the authors: - Léon van Wouwe, Volv Global’s clinical innovation director and lead author, said industry still does not adequately understand the lived clinical experience of patients before and after diagnosis. - Christopher Rudolf, Volv Global’s CEO and founder, said rare disease development is trapped in a loop of small estimates, fragile business cases and shelved programs. - Mahdi Farhan said he is motivated to find a treatment for Usher 3 patients as vision and hearing continue to decline. - Professor James A. Levine said his experience as a physician-scientist and parent informed his support for the effort. - Bernd Rosenbichler said his son Ben’s Alström syndrome diagnosis and progressive loss of sight and hearing drove his commitment to the issue.

What's next: - The paper calls for drug developers, researchers and policymakers to challenge prevalence modeling, biological understanding and cost assessment at the same time. - Its central bet is that better data and AI tools can make more rare disease programs look viable earlier, which could help move more treatments toward patients. - Volv Global’s LinkedIn profile is listed in the release for more information.