Setting an appropriate price for an innovative orphan drug is increasingly difficult in today’s resource constrained health care systems. What constitutes the value of orphan drugs is mainly perceived as empirical and a function of their rarity. The conventional cost-effectiveness (CE) approach analysis implies the use of a CE threshold. The determination of this threshold for orphan drugs is a contrived exercise and can make the pricing decision hard to justify in the eyes of many stakeholders, notably clinicians and patients. In this conceptual research, we explore the use of a value-based pricing mathematical function to link the incremental value brought by innovative orphan drugs to their prices. This function depicts the incremental value-based price (Y-axis) against the incremental value (X-axis). Value is holistically considered and embraces multiple clinical, humanistic and societal criteria that can be weighted by stakeholders (clinicians, patients, caregivers and payers). The incremental value is thus assessed throughout multi-criteria decision analysis (MCDA) and is finally embodied into a unified value score. The value-based price is expressed as a function of this value score. The exact shape of this value-based pricing function is obviously unknown. However, we stipulate that it has to satisfy two necessary conditions: 1) growing, and 2) bounded by the maximum willingness-to-pay (WTP) for the ultimate achievable incremental value (e.g. cure of the disease). We compare two functional forms: linear and sigmoid and we debate multiple WTP scenarios and perspectives. Finally, we conclude that this simple and transparent mathematical approach might prove useful to inform value-based pricing. When combined with MCDA, the approach makes more explicit the relevant value determinants and incorporates these determinants in a more holistic value and pricing framework for rare disease treatments. Empirical works, however, are needed to further substantiate the approach in the eyes of decision makers.