Elsevier

Translational Research

Volume 154, Issue 6, December 2009, Pages 314-322
Translational Research

Review Article
Drug development for orphan diseases in the context of personalized medicine

https://doi.org/10.1016/j.trsl.2009.03.008Get rights and content

Orphan diseases are diseases that are found in less than 200,000 patients in the United States, which is the cutoff point for the number of patients for a drug to be profitable. Because many thousands of orphan diseases exist in the aggregate (about 20 to 30 million Americans have orphan diseases), these patients are disenfranchised from drug development by the pharmaceutical industry. Orphan drugs are a large part of personalized medicine. The orphan diseases are often so rare that a physician may observe only 1 case a year or less. So proper treatment is a personalized encounter between doctor and patient. Academic physician-scientists have tried to fill this therapy vacuum by working on developing orphan drugs. But many disincentives are involved, which include career disincentives, lack of funding, and the multiple areas of expertise that are required. Positive developments include formation of the National Organization for Rare Diseases, the Orphan Drug Act, the development of a grant program to fund orphan drug development, the formation of the National Institutes of Health Office of Rare Diseases, and the passage of orphan drug legislation by other countries. Progress has increased, but the 300 orphan drugs and devices approved in the last 25 years are still only a drop in the bucket compared with the many thousands of orphan diseases. I believe we must do better. I present my own 2 examples of the positive and the negative aspects of orphan drug development, and I end this article by giving recommendations on how we might succeed both in developing more orphan drugs and in rescuing the pharmaceutical industry from its impending economic collapse.

Section snippets

National Organization for Rare Diseases (NORD)

In 1982, Dr. Jesse Thoene and I organized the first orphan disease conference, in Ann Arbor, to bring together scientists interested in orphan drugs with drug company representatives, representatives of lay organizations involved with orphan diseases, and various types of administrators and political representatives. The results of this meeting were published.2 Two subcommittees of this meeting recommended formation of an umbrella organization concerned with all orphan diseases.2 From this

Review of Progress in Developing Orphan Drugs

Given the above positive developments, what progress are we making on developing orphan drugs? Certainly, more attention is being paid as witnessed in the increase in publications on orphan diseases and orphan drugs during current times as compared with when the above reviewed activities were beginning (Table I). What about actual orphan drug FDA approvals? It has been stated that only 10 orphan drug approvals occurred in the decade prior to the passage of the Orphan Drug Act (1983) and more

Zinc for Maintenance Therapy of Wilson's Disease

Wilson's disease is an inherited disease of copper accumulation and copper toxicity.6, 7, 8, 9 It is rare—there are about 10,000 patients in the United States. The copper toxicity causes liver damage and in about half the patients brain damage, with patients who present with liver disease or a movement type neurologic disorder, most typically during the 2nd and 3rd decades of life.

I was giving patients with sickle cell anemia relatively high doses of zinc to try to treat their disease.10 We had

The Future of Orphan Drug Development in the Context of Personalized Medicine

As I have said earlier, orphan disease treatment is almost synonymous with personalized medicine. It is different and more personalized than treating large populations, where the doctor's favorite statin will control cholesterol, or favorite sleeping aid will control insomnia, or favorite antihypertensive will control blood pressure, in just about everybody. Treating an orphan disease is a very personalized experience, because the physician observes so few of these patients, and even within the

Final Thoughts and Recommendations

As I have said repeatedly, research on orphan drugs is vitally important. Currently, 20–30 million people are waiting to be helped. Yet it is very personalized, because in the end a physician must be able to select and prescribe the treatment that is effective and safe for a single patient, even though that may be the only patient with that particular disease the physician sees that year.

Many good things have happened to facilitate orphan disease treatment research, which include NORD, the

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