Making every patient count: designing robust trials in rare liver diseases 

Jennifer Schranz, SVP, Global Head of Rare Diseases  

Small populations, high stakes 

For years, rare disease research has been shaped by the belief that small patient populations inevitably produce limited evidence, forcing scientific rigor to yield to the constraints of scarcity. This narrative is now being actively challenged. The FDA’s 2025 rare disease guidance framework signaled a clear shift, formally recognizing that single pivotal trials and innovative study designs can meet approval standards even when populations are small. In many ways, constraint has catalyzed a more precise and intentional form of science. This has driven the field toward tighter, more meaningful endpoints, adaptive methodologies and outcome measures engineered to detect real clinical signals from very small numbers, proving that rarity does not have to mean compromise. 

When numbers are limited, trial design does what volume cannot 

When patient numbers are limited, thoughtful clinical trial design becomes essential. For Ipsen, this starts with designing for the disease itself, with a focus on how it affects patients’ lives, endpoints shaped around that reality and regulatory strategy led by the science. In conditions like primary biliary cholangitis, progressive familial intrahepatic cholestasis and Alagille syndrome, where patients often wait years for an accurate diagnosis, those who engage in research do so as active partners with us, shaping what we measure and how we measure it. In cholestatic liver diseases, that means capturing not only biomarkers of disease activity but the symptoms that define daily life – most notably the crushing fatigue and relentless itch – through validated tools held to the same rigor as any clinical measure. We have seen this approach work; randomized controlled trials across rare cholestatic conditions in both children and adults have already achieved regulatory approvals in the EU, US and beyond. 

A new standard, not a lower one 

We are witnessing the emergence of a new standard in rare liver disease research – one that Ipsen has helped to shape through more innovative, adaptable scientific approaches. This progress is not defined by incremental change, but by a willingness to challenge established boundaries and rethink how evidence is generated in small populations. The legacy of this work will extend far beyond the therapies available today. It will be seen in the scientific and statistical limits the field was required to push – redefining what rigorous, meaningful evidence can look like in rare disease research. Through this approach, Ipsen is helping to reshape expectations across the rare disease landscape, demonstrating how much more can be achieved when science is designed around both biological complexity and patient reality.