Abstract

Objectives

To examine ultraorphan drugs in terms of incremental health, costs, and cost-effectiveness compared with more prevalent disease drugs.

Methods

We identified Food and Drug Administration drug approvals from 1999 to 2019. For drugs approved for multiple indications, we considered each drug-indication pair separately. Utilizing Food and Drug Administration’s orphan drug designation and US disease prevalence, we categorized drug-indication pairs as: ultraorphan (200 000), and nonorphan (≥200 000). We searched the PubMed database for cost-effectiveness analyses and comparative effectiveness studies. We excluded manufacturer-funded studies. We extracted estimates of incremental health gains in terms of quality-adjusted life-years (QALYs) and incremental costs associated with drug-indication pairs compared with the standard of care at the time of their approval. We compared QALY gains, added costs, and incremental cost-effectiveness ratios (ICERs) using the Kruskal-Wallis, Mann-Whitney U (MWU), and Kolmogorov-Smirnov (KS) tests.

Results

Median incremental QALYs, costs, and ICERs differed across nonorphan, “other” orphan, and ultraorphan categories (Kruskal-Wallis P .01).

Conclusions

Novel ultraorphan drugs typically offer larger incremental health gains than drugs for more prevalent diseases, but because of their substantial added costs, are typically less cost-effective.