How Orphan Drugs Came to Be Called “Orphan”

By Frank J. Sasinowski & Andrew J. Hull* -

Even though we often blog on orphan drug developments (see two of our most recent posts here and here), many may be unaware of the origin of the term “orphan.” Today, we may think that the term “orphan” was created by the Orphan Drug Act of 1983 (“ODA”). The ODA incentivizes the development of drugs to treat rare or “orphan” diseases. The ODA, however, provides absolutely no explanation for its use of the word “orphan.” Instead, it is necessary to go back further into history to understand the term’s origin.

The first written use of “orphan” in the context of therapeutic drugs was in a 1968 editorial comment entitled “Therapeutic Orphans” and published in The Journal of Pediatrics by Harry Shirkey, M.D. (see a reprinted copy of the article by the American Academy of Pediatrics here). Dr. Shirkey, a pediatrician in the Children’s Hospital in Birmingham, Alabama, was writing about the inequality that he saw in the development of drugs to treat children. Since few drug developers found it worth the cost of studying the efficacy and safety of drugs in children, Dr. Shirkey argued that, “[b]y an odd and unfortunate twist of fate, infants and children [were] becoming ‘therapeutic or pharmaceutical orphans.’” As a result of these lack of studies, most drugs contained disclaimers stating that the drugs should not be used in children, but, nevertheless, often children were prescribed these drugs with little to no knowledge of possible adverse reactions or any estimate of benefit. Dr. Shirkey decried this abandonment, or “orphaning,” of the pediatric population, stating that “[i]t seems unfair that the use of some drugs will be denied based on relatively infrequent use and small sales potential.”

After the publishing of Dr. Shirkey’s editorial comment, others began to apply “orphan” to other types of diseases that were similarly abandoned or orphaned. For example, many began to use the term to describe diseases that primarily affected those in less-developed parts of the world.

In the 1970s, the FDA began to investigate what it saw as a gap in the development of therapies for certain patient populations. In June 1979, an interagency taskforce issued a report to the Secretary of Health, Education, and Welfare (predecessor to Health and Human Services) addressing the lack of development of “significant drugs of limited commercial value.” The taskforce found that many drugs essential for diagnosis or treatment of “rare diseases” were not available mainly because “research, development and production are deemed too expensive relative to expected economic return.”

The taskforce on significant drugs of limited commercial value was chaired by FDA’s Associate Director for New Drug Evaluation, Marion J. Finkel, M.D. After publication of the report, Dr. Finkel was named as FDA’s first Director of Orphan Products Development in 1982, and, in this position, she played an instrumental role in FDA’s implementation of the ODA. Additionally, it was Dr. Finkel who championed use of the term “orphan” exclusively for therapies for rare diseases. Accordingly, even though she did not coin the term, we have Dr. Finkel to thank for our use today of the term “orphan.” Additionally, we can also be grateful that her doing so moved us away from the less euphonious term: “significant drugs of limited commercial value” (imagine a law entitled the “Significant Drugs of Limited Commercial Value Act of 1983”!).

The development of the term “orphan” in the context of developing cures for rare diseases and conditions has had a long and interesting evolution. At each step of the process, however, one thing has remained the same: those involved in creating and developing this term have been motivated by their concern for patients with rare diseases. Together, these individuals have worked to create a better system that advances the development of drugs for patients suffering from ORPHAN diseases.

* Admitted only in Virginia. Work supervised by the Firm while D.C. application pending.