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Orphan Drug Act, United States, Drug Development, Medical Research and Development, Rare Diseases, Drug Price Points, Critique


The Orphan Drug Act (ODA) [1], first enacted in the United States in 1983, was set up to encourage the development of drugs for rare diseases. At that time, drug therapies for such diseases were rarely developed. Three decades later, a growing proportion of industry research and development (R&D) [2] and regulatory drug approvals [3] target diseases affecting fewer than 200,000 persons in the United States, the prevalence-based threshold of rare disease under the ODA.

In a new article published in PLOS Medicine, Aaron Kesselheim and colleagues document an embedded trend: within the increasing number of drug approvals targeting rare diseases, there is a substantial minority of biomarker-defined subsets of more common diseases, especially cancers [4]. Commentators have long worried about this phenomenon of “salami slicing” common diseases for the purposes of drug approval because of the market advantages that orphan drug status confers [5,6]. Due to lower R&D costs (e.g., relatively small clinical trials or observational studies), expedited regulatory reviews, and minimal competition even after patent and ODA market protection expire, rare-disease-targeting orphan drugs are now amongst the most expensive and profitable drugs on the market in the world [7].

Most of the policy and scholarly response to the orphan drug pricing problem to date has been to explore new ways to evaluate orphan drug performance following regulatory approval [8,9]. However, there is little indication that health care payers are successfully pushing back on drug price points. Meanwhile, the findings of Kesselheim and colleagues underscore how the operation of the ODA upstream—at the point of regulation—serves to expand the scope of the problem. With the increasing ability to more precisely identify biomarker-defined subsets of disease, it is perhaps time to re-examine how the ODA distinguishes rare versus common forms of disease or, even more fundamentally, what the ODA is meant to achieve.

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Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.