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FDA Consumer magazine
May-June 1999
by John Henkel
Deborah Kaback noticed the turnaround in her son, Matthew, right away. After spending his first five years of life fighting fatigue, crippling lung congestion, and other symptoms of cystic fibrosis, his condition improved quickly when he started taking a drug called Pulmozyme (dornase alpha) in 1994.
"His energy level soared and has stayed [high] ever since," says Kaback. "Although it hasn't prevented lung infections entirely, I believe that it has helped reduce the frequency."
Infections also were a big concern for Kim Payne, whose son, Brian, was able to halt one menacing type of cystic fibrosis-related lung infection by using the antibiotic TOBI (tobramycin). He took the drug through two years of clinical trials starting in 1995, when he was 15, and continued the regimen after the drug's approval in 1997. "TOBI allowed him to have a normal and very healthy high school experience," says Brian's mother.
Success stories like these are common among cystic fibrosis (CF) patients nowadays. But as recently as the early 1980s, tragic tales were the norm. CF patients faced a life that was miserable and short. Children with the disease rarely lived beyond their early teens. Now, CF patients often live into their 30s, some even into their 50s. What's made the difference? For countless sufferers of rare or "orphan" diseases such as CF, the improved outlook is due in part to the Orphan Drug Act of 1983, which has helped make treatments such as Pulmozyme and TOBI available.
What Is an Orphan?
The Orphan Drug Act defines an orphan disease as a condition that affects fewer than 200,000 persons in the United States. More than 5,000 of these rare conditions exist in about 20 million Americans, according to the National Organization for Rare Disorders (NORD). Because no one would "adopt" the products to treat these diseases in the days before the law, they became known as "orphans."
An orphan disease may affect only a few thousand people--some, such as infant botulism, have patient populations of less than a hundred--so the potential for a company to profit from developing an orphan treatment is small.
This means that few firms, including large pharmaceutical companies, have been interested in investing the time and money in orphan products, says NORD president Abbey Meyers.
So for years, patients suffering from orphan diseases such as Gaucher's disease, rare cancers, hemophilia, multiple sclerosis, and Parkinson's disease simply were out of luck. With no financial incentives available, companies couldn't risk the investment. Other possible development outlets, such as universities or research hospitals, often lacked the capital or business savvy to develop treatments for small patient groups.
Orphans on a Roll
Pharmaceutical companies did, however, develop a few drugs of limited commercial potential in the 1960s and 1970s and even provided some at little or no charge. For example, the industry marketed Mithracin (plicamycin) to treat testicular cancer before the Orphan Drug Act was passed.
But by the early 1980s, only a handful of orphan treatments existed. A series of events, however, thrust the orphan issue into the public eye (see "How TV Launched the Orphan Drug Act."), and in 1982 Congress passed legislation giving generous incentives to companies willing to adopt orphans and bring treatments to market.
Since the act was signed, FDA has approved 182 orphan products--including drugs and biologics (see chart). Sponsors have submitted 1,252 applications for orphan designation, of which FDA has granted designation to 917. Orphan designation allows a company to proceed with development and take advantage of the law's financial incentives.
In 1998, FDA approved 18 new orphan products to treat conditions that include:
While only drugs and biological products are eligible for orphan designations, regulations finalized in 1996 as part of the Humanitarian Use Devices (HUD) provisions of the Safe Medical Devices Act of 1990 created an exemption that makes it easier and less costly for manufacturers to bring orphan-related medical devices to market.
Under the exemption, FDA allows these devices to be sold if sponsors can show they are safe and have a probable benefit for patients. Sponsors do not need to prove effectiveness to get a HUD designation. Since July 1996, FDA has allowed 17 devices to be marketed as HUDs. None of these has yet received full FDA approval as a medical device, which would require clinical trials to prove effectiveness.
Powerful Incentives
While orphan interest from the large pharmaceutical firms remains limited in the wake of orphan law--only about 15 percent of applications come from the giant drug makers--some small companies have sprung up just to develop and market orphan products. In fact, orphan law can be credited with helping establish the American biotechnology industry, says John McCormick, M.D., deputy director of FDA's Office of Orphan Products Development.
"In the early '80s, patent laws for biotechnology were vague, so biotech companies had little protection for their products," says McCormick. He says a provision of the law that grants seven years of exclusive marketing rights is tantamount to a patent and allows a small company to proceed without fear that a competitor might market a similar product for the same condition. "Because many orphan diseases lend themselves to treatment with biotech products," says McCormick, "the exclusivity incentives have worked beautifully to foster innovative treatments by sheltering them from competition."
Though marketing exclusivity is likely the law's most powerful industry incentive, McCormick says, other provisions for orphan-designated products also are important motivators, including:
Meyers says NORD, which is a grassroots coalition of 140 voluntary rare-disease groups, is pleased with the approval rate of orphan products. "The thing that is so encouraging," she says, "is that the rest of the world has seen how the American [orphan] law has been so effective, and now they feel they have to have similar programs." Indeed, the European Union, Japan and Australia all have begun orphan programs of their own based on the U.S. model.
But are the goals of the original act on track 16 years later? "Definitely," says FDA's McCormick. "I think the framers of the act are all pleased as punch."
John Henkel is a staff writer for FDA Consumer.
Before the 1980s, victims of many rare disorders faced suffering and even death, with little hope for treatment. It simply was not cost effective for pharmaceutical companies to spend millions developing treatments that would only be used by a few hundred or a few thousand patients.
The landscape changed, however, when Congress passed a bill in 1983 that created incentives for developing products for these rare, or orphan, diseases. But the Orphan Drug Act navigated a long, bumpy road before becoming law, several times appearing to be doomed. While many in the rare disease community credit increased awareness of the orphan problem to an array of groups, including Congress, industry and the news media, others give thanks to a person who, in the early '80s, was riding high with a hit TV show: actor Jack Klugman.
"There just wouldn't be an Orphan Drug Act without Jack Klugman," says Abbey Meyers, president of the National Organization for Rare Disorders. "The issue simply wouldn't be known to the public without him."
Klugman used his weekly TV medical drama, "Quincy," on two occasions to spotlight the plight of rare-disease patients, prompting a huge outpouring of support that ultimately pushed the orphan drug bill through Congress.
Meyers recalls that the situation was bleak before Klugman's involvement. Rep. Henry Waxman (D.-Calif.) had received a call in 1980 from the mother of a boy, Adam Seligman, whose drug treatment for the rare disorder Tourette syndrome had been seized at the Canadian border. Because the drug was approved in Canada but not in the United States, Adam's doctor had arranged to bring the drug from Canada for his patient. Adam's mother was frantic that her son was about to run out of medication.
For his part, Waxman held hearings to gauge the extent of the rare disease problem. Witnesses, including Adam, gave emotional testimony, but the hearings were sparsely attended. However, one person present was a reporter from the Los Angeles Times, who wrote a story about the orphan issue.
The next day, Jack Klugman's brother, Maurice, saw the Times article. He told the story to Jack, who decided to create a "Quincy" episode devoted to Tourette syndrome and the orphan problem. After it aired in March 1981, viewers responded by sending thousands of letters to Jack Klugman voicing support and asking how they could help.
With the issue now more visible, Waxman introduced an orphan drug bill and held a second hearing--this time with Klugman as a witness. With Klugman's celebrity on board, the news media covered the issue extensively, and even greater popular support followed. But when the bill stalled in Congress, Klugman put together another "Quincy" episode, this time mirroring the real-life holdup of the bill taking place on Capitol Hill. He used 500 "extras," who were real victims of orphan disorders. By the time the show aired in 1982, the House had passed the bill, but it was on hold in the Senate. It later passed but faced veto by President Reagan, in part because the administration objected to the bill's tax credits.
Rare-disease activists then took out full-page ads in major newspapers urging the president to sign the bill. It worked. On Jan. 4, 1983, the Orphan Drug Act became law.
--J.H.
Additional details on rare diseases and orphan products are available from:
FDA Office of Orphan Products Development
HF-35
5600 Fishers Lane
Rockville, MD 20857
301-827-3666
www.fda.gov/orphan/
National Organization for Rare Disorders Inc.
P.O. Box 8923
New Fairfield, CT 06812-8923
1-800-999-6673
www.rarediseases.org
Questions concerning the editorial content of FDA Consumer should be directed to FDA's Office of Public Affairs.
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