Orphan Products: Hope for People with Rare Disorders

by Food and Drug Administration (FDA)

Alice Parker remembers well the time not long ago when her eyes closed and didn't reopen.

It was like her body had pulled shades over her sight and wouldn't let them go. Her eyes still worked fine, but, blocked by locked-shut eyelids, they couldn't perform. At age 49, afflicted with the rare muscle disorder blepharospasm, she became, in essence, blind.

"I was unable to function normally," says Parker (not her real name). "I was bumping into things." Her only relief came from wearing uncomfortable glasses with special devices that pry the eyelids open. Her bout with blepharospasm, which began in 1985 as overactive blinking, eventually became so debilitating she had to quit her job.

But today, thanks in part to a law passed 12 years ago, Parker has regained her sight and is working again. She's not cured, but an injectable biological product made possible by the Orphan Drug Act of 1983 allows her to lead a life close to normal.

Blepharospasm is an "orphan" disease — a rare disorder affecting a small population. According to the Benign Essential Blepharospasm Research Foundation, about 25,000 people have the disease in this country. Traditional treatments such as surgery haven't always worked and have left patients disfigured. Many sufferers once resigned themselves to a life of functional blindness.

But now, the biologic Botox (botulinum toxin type A), aided in development by the Food and Drug Administration's Orphan Products Program, has rescued many patients with blepharospasm and other muscle disorders. Approved in 1989, Botox is derived from the same deadly bacterium that causes botulism. Yet, injected in the proper dosage, it relaxes certain muscles seized by spasms.

Mitchell Brin, M.D., a New York neurologist who conducted pre-market clinical trials of botulinum toxin, says, "Before the toxin, less than 10 to 20 percent of [blepharospasm] patients could be helped. Now we can help more than 90 percent."

Adopting 'Orphans'

The Orphan Drug Act defines orphan products as ones used to treat diseases or conditions affecting fewer than 200,000 persons in the United States. Such small patient populations reduce profit potential for sponsors, so the act grants special privileges and marketing incentives. In the case of Botox, Allergan Pharmaceuticals "adopted" the biologic from San Francisco ophthalmologist Alan Scott, M.D., and now markets it to patients nationwide.

Blepharospasm is one of more than 5,000 known rare disorders that together affect as many as 20 million Americans, according to estimates from rare-disease groups. For years, these conditions condemned patients to a life of pain and suffering. People with diseases such as hemophilia, multiple sclerosis, cystic fibrosis, rare cancers, and scores of other disorders could see little relief in sight. Companies were reluctant to invest the time and money necessary to develop treatments because the market was so small. Other outlets, such as research hospitals and universities, often lacked the capital and business expertise to develop treatments for limited patient groups. Today, approved treatments are available for all these conditions (see accompanying article).

To be sure, pharmaceutical manufacturers were not completely inactive in the orphan arena. Through the 1960s and 1970s, industry pursued development of numerous drugs of limited commercial value and even provided some at little or no charge. For example, industry developed the pharmaceuticals Mithracin (plicamycin), which treats testicular cancer, and the fungicide flucytosine before the Orphan Drug Act was passed.

By the early 1980s, however, the list of true orphan advancements still was woefully short, says Marlene Haffner, M.D., director of FDA's Office of Orphan Products Development. The plight of orphan-disease patients remained largely unaddressed. Clearly, the only way to change things was for all parties — industry, government, medical professionals, patients, and legislators — to find a way to bolster orphan products development. The catalyst for action was the Orphan Drug Act.

Orphans Bounce Back

With the act's passage, Congress had, for the first time, given research groups and drug companies financial incentives to develop and adopt orphans. Just as importantly, the act focused intense public, government and industry attention on the plight of rare-disease sufferers.

Today, new orphan products come on the market regularly. Some companies have even sprung up to develop and market orphan drugs exclusively. Since the act's passage, FDA has approved 108 orphan products (see Table, or Chart if your browser doesn't support tables), a number some say will at least double in the next decade. "I wouldn't be surprised if there are 200 approved orphan drugs by 2003," says Abbey Meyers, executive director of the National Organization for Rare Disorders (NORD), a grassroots cooperative of more than 100 nonprofit agencies. NORD played a major part in getting the act passed and now offers services such as an extensive database through which rare-disease sufferers and their families can learn more about orphan disorders.

The drug industry also made important strides to boost development of orphan products. In 1981, the Pharmaceutical Research and Manufacturers Association of America (PhRMA) established the Commission on Drugs for Rare Diseases to seek out promising orphan drug candidates and bring them to the attention of companies willing to develop them into useful products. Says Tom Copmann, Ph.D., a PhRMA assistant vice president, the commission canvasses sources such as medical journals, medical schools, and individual researchers to find orphan hopefuls. "Then," he says, "we endeavor to find [each orphan] a 'parent.'"

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.