GAO Finds Trouble With Orphan Drug Designations

The Government Accountability Office (GAO) recently issued a report that finds serious deficiencies with the ways in which the Orphan Drug Act is administered by the FDA.

Drugs that treat rare diseases are granted various incentives under the Orphan Drug Act of 1983 if they meet criteria related to the size of the rare disease population (under 200,000 people) that can be effectively treated by the drug in question. Demand for orphan designations has grown since the act came into force, with the number of applications tripling in the last decade alone.

In its review of the FDA’s oversight of orphan drugs, GAO found that, while the FDA generally applies consistent criteria to applications for orphan drugs, the agency does not consistently ensure that all required information—such as elements of the drug’s regulatory history and other orphan designations for the product or for the disease state it is intended to treat—is appropriately recorded and used in the regulatory decision-making process.

In 1 case described in the report, a reviewer did not record any prior orphan drug designations for a specific disease despite the fact that 36 related orphan designations were already approved for the disease state at the time of the review. Furthermore, the FDA does not provide instruction on how to use such information in the evaluation of orphan drug applications.

In addition, while the FDA instructs reviewers to consider independent evidence in verifying population estimates for those affected by specific rare diseases, GAO found that in 23 of 148 review templates, reviewers did not include independent verification of population estimates.

GAO also found that orphan drug approvals were concentrated in 2 areas during the period from 2008 to 2017: hematology (10.8%) and oncology (42.5%). In total, there were just 27 therapeutic areas, with 7 of those areas already having 10 or more approved orphan drugs. Of 351 marketing approvals for orphan drugs during this time period, only 252 were for unique drugs, as many products were approved for more than 1 orphan indication. Some drugs were approved to treat 3 or more orphan indications, with products like bevacizumab (Avastin, which faces an oncoming challenge from biosimilar Mvasi) having 9 orphan indications.

In 2017, Kaiser Health News (KHN), together with NPR, reported that the orphan drug program was being used by drug manufacturers to generate additional profits and protect the markets for medicines that already serve large numbers of patients. According to KHN, blockbuster drugs already on the market, like adalimumab (Humira) and trastuzumab (Herceptin), were granted orphan approvals and extra incentives and exclusivities that effectively block biosimilar competition.

GAO called on the FDA to clarify for its reviewers how to use required information to ensure consistency and quality of orphan designation reviews, particularly as demand for these designations grows.