Drugs & MedicationsHealthcare PolicyHuman Interest


In the pharmaceutical world there exists an entire class of drugs with which the public is largely unfamiliar and most physicians have limited working knowledge. These drugs, called Orphan Drugs, are developed to treat diseases which are considered rare and are not often diagnosed. They are used for a specific disease or disorder and thus have a narrow range of use and aren’t prescribed for any other reason. They are niche products. Drug companies have little interest in spending millions of dollars on research and development for drugs that are prescribed infrequently and have little chance of being profitable. In fact, in the decade between 1973 and 1983, fewer than ten such drugs were developed. A glaring deficiency! All that has changed, however!

In 1983, in one if it’s finer moments, the U.S. Congress passed into law the ORPHAN DRUG ACT. This law gave drug companies economic incentives to develop treatments for rare diseases—diseases and conditions that affect fewer than 200,000 people in the U.S. It established within the Food and Drug Administration (FDA) an “Office of Orphan Products Development” (OOPD) whose purpose it was to determine if a drug qualified for “orphan” drug status. Since the passage of this act, over 600 “orphan” drugs have been developed. It’s amazing, especially for individuals diagnosed with one of the 7000 rare, orphan diseases. The OOPD has a division called the Genetic and Rare Disease Information Center (GARD) which lists these diseases and the orphan drugs approved for their treatment. It is a valuable resource that can be found at raredisease.info.NIH.gov. The list is quite comprehensive. 

Also, within the OOPD, the following programs exist:

  1. Orphan Drug Development Program: The agency that provides orphan status to drugs and biologicals which are “intended for safe and effective treatment, diagnosis, or prevention of rare diseases/disorders,” but “are not expected to recover the costs of development and marketing.”
  2. Rare Pediatric Disease Priority Review Voucher Program: A “sponsor” who receives approval for a drug or biological used for a rare pediatric disease may qualify for a “voucher that can be redeemed to receive priority review of a subsequent different drug.
  3. Humanitarian Use Device Program: “Designates medical devices that are intended to benefit patients in the diagnosis and treatment of a disease or condition that affects fewer than 8000 individuals in the U.S.”

The OOPD also provides grants for clinical research that tests the safety and efficacy of drugs, biologicals, and medical devices used in rare diseases; for the study of the natural history of rare diseases to advance medical product development; and for pediatric medical device development.

Examples of “rare diseases” are alpha-1antitrypsin deficiency, Hansen’s disease, and Lynch Syndrome. Have you ever heard of these conditions? I have but have never seen any of them. 

Alpha -1 antitrypsin deficiency is a genetic disorder of the serum proteins that if left untreated leads to emphysema and cirrhosis of the liver. Its approved orphan drug is Prolastin.

Hansen’s Disease,better known as leprosy, is an infectious disease diagnosed in only 63 patients in the U.S. in 2015. It’s orphan drug is Lamprene.

Lynch Syndrome is a genetic (hereditary) condition of the colon that frequently leads to the development of colon cancer. It’s approved drug is Leucovorin.

You’ve probably never heard of any of these drugs. Again, I have but have never prescribed any of them. They are all very uncommon and used infrequently.

Dr. G’s Opinion: Passage of The Orphan Drug Act was a great humanitarian boost to the 25-30 million Americans who live with rare diseases. That means a large number of people are now benefitting from the drugs and treatments developed as a result of the economic incentives provided to drug manufacturers. Who can know how much this law has lengthened the lives of these patients and improved their quality of life. I think it’s important to be aware of this program and know that sometimes the Congress gets it right. The term “orphan” in my mind is a misnomer. I think it lends a negative connotation and leads to a misunderstanding of the true purpose of these drugs. Alternate terms would be “unique,” “definitive,” “precise,” “exclusive,” or “categorized” drugs. It gives the class a legitimacy that “orphan” omits.  

Since 2000, “new molecular entities,” NME’s, “constituted 80% of the drugs approved (by the FDA).….and 40% of biological agents were awarded orphan drug status….pharmaceutical firms have shifted their focus”….to those drugs that “advocacy groups and patient’s organizations have made a priority for rare diseases.” “Regulatory and economic incentives have led to substantial improvements the development of drugs for these diseases.”

Of 35 countries surveyed, 27 had Orphan Drug laws. Each country’s policies differ so availability of orphan drugs relies completely on the regulations and legislation established in that country. This trend is obvious from observing ads seen on TV. Drugs for conditions most doctors rarely see are advertised as if they are common, everyday disorders. “Ask your doctor to prescribe drug ABC for your disease which occurs in 1 in a million people.”  The emphasis has shifted. 

The markets for high blood pressure, cholesterol, antibiotics, and anti-depressants are pretty-well saturated, and new agents in those categories are largely copies of already-effective and successful drugs. They have a hard time gaining preferred status over already-established products. I would tell the drug rep who tried to sell me on his new statin, the 7th one in the class, “Why would I ever prescribe your drug over XYZ? XYZ works fine and has for years. Why would I change?” Thus the industry’s shift to drugs for less common disorders. 

Orphan Drug laws are a good thing. They allow patients to be given drugs that are infrequently used and occasionally experimental. Now that we know treatment is available for our rare disorder, our next monumental task is getting our health insurance company to move the roadblocks put up to keep us from being able to use it! Good luck with that! 

References: Attwood MM, Rask-Andersen M, Schioth HB. Orphan Drugs: Their impact on Pharmaceutical Development Trends Pharmacol Sci 2018 Dec;39(12):1077.

Tambuyzer E. Rare Diseases, Orphan Drugs and their regulation: Questions and misconceptions. Nat Rev Drug Discov 2010 Dec;9(12):921-929.

Gammie T, Lu CY, Babar ZU. Access to orphan drugs: A Comprehensive review of legislation, regulation, and policies in 35 countries. PLoS One 2015 Oct 9;10(10).

Rama P, Chawla S. Orphan Drugs: trends and issues in drug development Basic Clin Physiol Pharmacol 2017 February 6. 

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  1. Wow I guess I didn’t know you had shingles.
    Just finished reading the shingles and orphan drug blog. Both were interesting and I learned something.

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