Date of Award

Summer 8-2022

Document Type


Degree Name

Doctor of Philosophy (PhD)


Pharmaceutical Sciences

First Advisor

Enrique Seoane-Vazquez, PhD.

Second Advisor

Rosa Rodriguez-Monguio, PhD., MS

Third Advisor

Lawrence M. Brown, PharmD, PhD., FAPhA

Fourth Advisor

Marc L. Fleming, BSPharm, MPH, MS, PhD.


Introduction. Rare disease drug approvals have accelerated significantly in recent years. Even with these advances, patients continue to face challenges in receiving treatment, with most rare diseases lacking any approved treatments. Moreover, even when a treatment is available, it does not always reach the patients who benefit from it.

Objectives. This dissertation assessed the characteristics of orphan drug designations and approvals and the factors associated with the time lag between orphan designation and approval in the US from 1983 to 2021. It also evaluated the treatment cost of orphan and non-orphan drugs and factors explaining the treatment cost of new drugs approved by the FDA from 2017 to 2021.

Material and Methods. We collected data for orphan drugs approved in the US from 1983 to 2021 from the FDA online databases Drugs@FDA and Orphan Drug Product Designations and Approvals. The wholesale acquisition cost (WAC) for orphan and non-orphan drugs was collected from the REDBOOK® (IBM®Micromedex®). Descriptive statistics and linear and logistic regressions were performed.

Results. From 1983to 2021, the FDA granted 6,137 orphan designations, including 59.1% chemical entities and 40.9% biologics. Drugs with prior orphan designations, drugs sponsored by companies with previous experience with orphan approvals, and orphan indications for pediatrics and adults had a high likelihood of approval. The time lag from orphan designation to approval was negatively associated with the number of prior orphan approvals of the sponsored company and the implementation of the FDA Orphan Drug Modernization Plan. From 2017 to 2021, there were 242 drugs approved by the FDA and marketed in the US, including 48.8% orphan drugs and 51.2% non–orphan. The treatment cost at market entry was 17.1 times higher for orphan than for non–orphan drugs. Therapeutic biologics, orphan status, US sponsor companies, chronic use, treatment intent, and indications for oncology or genetic disorders were associated with higher treatment prices.

Conclusions. The increase in orphan drug designation, approvals, and prices in the US were related to regulatory changes and the sponsor companies' characteristics. The cost per treatment for drugs marketed in 2015-2021 was significantly higher for orphan than non-orphan drugs.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Wednesday, August 28, 2024