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Market Exclusivity for Drugs with Multiple Orphan Approvals (1983–2017) and Associated Budget Impact in the US

A Letter to the Editor to this article was published on 09 November 2020

A Letter to the Editor to this article was published on 09 November 2020



The Orphan Drug Act extends exclusivity of branded drugs by 7 years for each rare disease approval. By extending market exclusivity, manufacturers can forestall generic competition. We determined the prevalence of drugs with multiple orphan approvals, the duration for which manufacturers are able to maintain exclusivity using this mechanism, and the budget impact of these additional exclusivity periods on US spending on orphan drugs.


We analyzed a retrospective cohort of US orphan drug approvals filed between 1983 and 2017. Drug costs throughout this time period were measured using IQVIA claims data. We estimated additional years of exclusivity per drug per orphan approval using mixed-effects negative binomial regression. The budget impact analyzed potential cost-savings for exclusivity periods greater than 7 years after the initial orphan approval based on potential price reductions from the introduction of biosimilar/generic competition.


A total of 432 branded drugs were approved for 615 orphan indications, of which 108 had multiple indications. Market exclusivity, beyond the initial 7 years, increased by 4.7 years with two orphan approvals, and there were 3.1-, 2.7-, and 2.9-year extensions for three, four, and five approvals, respectively (p < 0.05). Drugs with five approvals averaged 13.4 additional years of exclusivity. Sixteen drugs had exclusivity periods extending at least 1 decade beyond the original exclusivity period. The potential budget impact of additional exclusivity was estimated at US$591 billion for 7 years following the end of the first approval.


Multiple blockbuster drugs have received exclusivity of > 10 years through the Orphan Drug Act, thereby delaying rare disease cohorts’ access to generic/biosimilar equivalents.

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Data Availability Statement

The budget impact model used in this analysis contains the aggregate information from the FDA on orphan disease populations, as well as patient costs from IQVIA claims. This model and these data are available as supplementary material for readers.


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The authors acknowledge funding from Arnold Ventures to conduct this study. We wish to thank John Shin for his collaborative work related to this study.

Author information




Each author contributed to the study as follows: conceptualization and design: WP, GA, RC; data acquisition and analysis: WP, SP, MS, RC; interpretation of the findings: WP, GA, SP, MS, RC; writing and editing of the manuscript: WP, GA, SP, MS, RC. All authors had access to the data at all times.

Corresponding author

Correspondence to William V. Padula.

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The authors were supported by an unrestricted grant from Arnold Ventures foundation to Johns Hopkins University to conduct this investigation.

Conflict of interest

The authors, WP, SP, MS, RC, and GA, have no perceived conflicts for the submitted research.

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Padula, W.V., Parasrampuria, S., Socal, M.P. et al. Market Exclusivity for Drugs with Multiple Orphan Approvals (1983–2017) and Associated Budget Impact in the US. PharmacoEconomics 38, 1115–1121 (2020).

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