Rare Disease Treatments: Orphans' Saving Lives

by Food and Drug Administration (FDA)

When Alison Ashcraft was 7, her family doctor called her parents in to tell them she had a rare disease, severe combined immunodeficiency, a genetic disorder made famous by the movie "The Boy in the Plastic Bubble." For children like Alison with no compatible bone marrow donor, there was no cure. The only treatment was repeated transfusions of gamma globulin, which still left her exposed to a host of infectious diseases.

After her diagnosis, her health worsened. "She would get a cold, it would turn into an infection, it would go to her lungs, and she would wind up in bed for six weeks with pneumonia," said her father, Aaron E. Ashcraft. She was fatigued, sleeping 20 hours a day, and unable to play more than five minutes of tennis, her favorite sport. She could not attend school from December until March because of her susceptibility to normal childhood infections and the possible dire consequences; even chicken pox could be fatal for Alison.

Then she was enrolled in a study of a drug called PEG-ADA, in which she was given adenosine deaminase, an enzyme her body failed to produce on its own. Last year, her sophomore year in high school, Alison was able to attend school through the winter for the first time. And one recent weekend she and her father played tennis 90 minutes without a break.

As recently as 10 years ago, PEG-ADA might never have come to market. But under the Orphan Drug Act, the federal government provided a grant to support development costs, provided federal tax credits, and offered other inducements, and PEG-ADA was approved by the Food and Drug Administration last March 23.

Other Rare Diseases

There are an estimated 5,000 known rare diseases that affect fewer than 200,000 people each, but which collectively affect between 10 million and 20 million people, according to estimates by the Pharmaceutical Manufacturers Association (PMA) and the National Organization for Rare Disorders (NORD).

The Orphan Drug Act has helped in the development of products to treat drug addiction, leprosy, hemophilia, and rare cancers, as well as diseases most people have never heard of, such as cryptosporidiosis (an infection caused by a protozoan parasite found in animals' intestines that causes diarrhea, fever, weight loss, and lymph node enlargement) and neurocysticercosis, a parasitic disease characterized by cysts in the brain and spinal cord.

The Orphan Drug Act was one of the reasons the pharmaceutical community was able to rise to the challenge of acquired immune deficiency syndrome, or AIDS. Pentamidine isethionate, used to treat a pneumonia that strikes many people with AIDS, and zidovudine (commonly called AZT), which prolongs the life of people with AIDS, were also developed under the Orphan Drug Act. According to Marlene Haffner, M.D., FDA's director of orphan product development, "Without the Orphan Drug Act, pentamidine may have been developed much later, as may have AZT, and maybe some of the others would never have seen the light of day."

Just the Beginning

The Orphan Drug Act has been in place more than seven years, but because of the length of time required to bring a drug to market, it is only just beginning to yield results. There have been 41 orphan drugs approved, most of them in the last few years, and, according to a recent trade publication, Orphan Drugs in Development, 133 products for 96 rare disorders are in the final stages of development.

"The first couple of years the Orphan Drug Act was in place, there was a lot of uncertainty about it, but the last four or five years it has really blossomed," said Abbey S. Meyers, NORD director. "In fact, what we're seeing now is a number of companies starting up specifically to pick up some of these orphans. If you can pick up an orphan drug and it has a market of $5 million to $20 million a year, a little company is very happy with it."

One of the new companies is Medical Market Specialties Inc. of Boonton, N.J., which has an investigational new drug application for Elmiron, said company president Richard C. Lufkin. Elmiron (pentosan polysulphate sodium) has been around for years, but the company is studying it to determine whether it can be used to treat a rare and painful bladder disorder, interstitial cystitis, which affects about 45,000 people in the United States, 90 percent of them women.

"Without the Orphan Drug Act, Elmiron would never have been pursued, because there would have been no [marketing] protection," Lufkin said. "After we got done with the [approval process], someone else could have made it and sold it without the research and development expense."

Recent Approvals

In 1989, eight new orphan products were approved for marketing, including epoetin alfa for the treatment of anemia associated with chronic renal failure, rifampin for anti-tuberculosis treatment, and cromolyn sodium for mastocytosis, which can cause hives, itching, bone pain, diarrhea, and chronic fatigue.

Also in 1989, FDA awarded 21 new grants for research into conditions such as: graft-versus-host disease; sickle cell anemia; Wilson's disease, in which copper accumulations in the liver cause cirrhosis and ultimately intellectual impairment; and neuroblastoma, a tumor of the adrenal glands or sympathetic nervous system that affects about eight out of every 1 million children.

Marketing exclusivity is one of the key features of the Orphan Drug Act because often a drug that has been around for years, and therefore cannot be patented, is discovered to be effective against another disease. A researcher might get approval to treat a few specific patients under an investigational protocol, but not have the time, money or expertise to guide it through the regulatory process for market approval.

"Some of these doctors were making these drugs by hand, and it occurred to them that if they get run over by a truck their patients would die, so it became important to them to find a commercial sponsor," said Meyers.

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.