OBJECTIVES:  Rarity is often considered as the driver of high orphan drug (OD) prices. The objective of this research is to identify the relationship between OD annual treatment cost in France and the rarity, as well as OD cost and acknowledgement of additional benefit (ASMR), and, finally, between ASMR and cost. METHODS: We identified all ODs approved by the European Medicine Agency (EMA) between January 2000 and May 2015. OD costs were calculated based on prices collected from the official French database Ameli and dosing regimen. Prevalence was available from the EMA website. We only considered first indications and initial prices. We looked at the correlation between each pair of the three variables and we identified the best fit equation type for cost/prevalence relation. RESULTS: Cost and prevalence were significantly correlated with R2 coefficient of 0.105 and Pearson correlation coefficient of -0.325 (p=0.0069). The best function fit was logarithmic, based on the root mean square error criteria. Lower prevalence was associated with higher costs, although, there was significant variation between costs for a similar prevalence. For products granted ASMR I-V median prevalence was 0.9, 0.8, 0.7, 2.0 and 1.3 per 10,000, respectively (p=0.01). Although no linear association was observed, products granted ASMR I- III (that open for premium price) had lower prevalence, than those with ASMR VI- V. Similarly, products with ASMR I-III had higher median costs: €33,940, €62,660, €49,724, respectively, while those for products with ASMR IV- V were €9,265 and €19,757. CONCLUSIONS: Rarity seems to be valued but does not seem to be the only parameter. Products with low and very low prevalence are associated with higher costs. This is consistent with the ASMR, as it appears to be closely correlated with the prevalence.