Adopting Orphan Drugs

By Claudia Wallis

Congress tries to encourage new remedies for rare diseases

In the summer of 1974, Concert Pianist Sharon Roubeck Dobkin suffered a series of seizures that left her with uncontrollable tremors, an inability to use her arms and legs or even hold her head upright. Two years and many doctors later, Dr. Melvin Van Woert of New York City's Mount Sinai Hospital identified the condition that ended her career: myoclonus, a nervous disorder that affects only 2,000 Americans. Van Woert had received a series of grants and special permission from the FDA to treat the disease with the experimental drug L-5HTP (L5-hydroxy-tryptophan), and Dobkin responded well to it. Within eight months she was able to walk with crutches and a neck brace and begin training for a new career as a medical assistant. Eventually she was well enough to have a child.

Her supply of L-5HTP, however, was always in jeopardy. No drug company was interested in developing a drug with such a small market. Van Woert had to buy it at a cost of $2,000 per kg from a biochemical supply house, where it was available for animal experiments, and sift it by hand into capsules. When his grant money ran out, Van Woert could no longer obtain the unapproved substance; nor could Dobkin legally do so. Van Woert's patients had to make do with far less effective medications. For Dobkin, 29, that meant returning to her wheelchair. "When I'm on L-5HTP I'm very well controlled, I have fewer tremors, I'm stronger," she says. "Without the medication, it is harder to walk, I fatigue easily and can't take care of my baby."

Dobkin is one of millions of Americans who suffer from diseases so rare there is no profit in making drugs to treat them. A pharmaceutical company's investment, up to $80 million for a new drug, cannot be recouped if only 100,000 people or fewer need the product. Such diseases and their drug treatments therefore are said to be "orphaned." Orphan diseases include cystic fibrosis, a deadly hereditary disorder that affects 40,000 Americans; Tourette's syndrome, a neurological abnormality characterized by tics and involuntary outbursts of swearing (100,000 Americans); Prader-Willi syndrome, a children's ailment that causes huge weight gains and often kills its victims before they are 20 (2,000); Wilson's disease, a condition marked by abnormal accumulation of copper in the liver and brain (1,000); Huntington's chorea, the degenerative disease of the mind and nervous system that caused the death of Folk Singer Woody Guthrie (14,000); as well as various rare cancers.

In recent years, the plight of orphan-disease victims has begun to capture national attention and stir concern. Beginning in 1980, several dramatic hearings of the House Subcommittee on Health and the Environment raised awareness of the issue with testimony from Marjorie Guthrie, the singer's widow, Actor Jack Klugman, whose TV show Quincy devoted an episode to Tourette's syndrome, and researchers like Van Woert. A study by the committee identified 134 drugs to treat orphan diseases, but found that only 58 were on the market or even under investigation by drug manufacturers. Furthermore, more than two-thirds of the orphan products that have been approved by the FDA over the past decade were developed with the help of Government or university funding. Says Subcommittee Chairman Henry Waxman: "That's an unhappy commentary on industry effort."

To redress the problem, California Democrat Waxman last year proposed legislation that would provide financial incentives to companies undertaking or phan-drug research. Last week such bills were overwhelmingly approved by the House and the Senate. Under the provisions of the House bill, drug companies were to receive a 90% tax credit for expenses incurred in orphan-drug development, but the Senate struck this credit and substituted an appropriation of $9 million. The House measure also called for a seven-year period of exclusive marketing rights for unpatentable orphan products. It provided that in the absence of any alternative treatment, orphan drugs would be made available to patients by drug firms during a testing period. A new orphan-products board would be created within the Department of Health and Human Services to oversee orphan-drug activities.

Not everyone is pleased with the legislation. In fact, the Administration issued a position paper last week opposing the measure. The statutory creation of an interagency orphan-products board, the Administration said, was superfluous be cause an equivalent panel existed within HHS. Waxman had already altered the bill to accommodate earlier Administration objections. Both the FDA and the Pharmaceutical Manufacturers Association had opposed a provision in the original bill that would have permitted approval of orphan drugs after one successful human clinical trial. With that provision dropped and other changes made, the P.M.A. now supports the bill, though it continues to defend its past record in producing orphan drugs. Some 40 drugs for rare diseases have been marketed since 1970, says Dr. George Goldstein of the P.M.A. He adds: "Industry has acted and will continue to act responsibly."

Dobkin, Van Woert and others who have spent years lobbying for orphan drugs remain skeptical. In the past year and a half, they have witnessed the creation of four orphan-drug commissions by both industry groups and the Government. So far they have had little impact on the availability of medications for rare diseases. "The private sector is really interested in developing drugs that make a lot of money; orphan drugs by definition do not," says Dr. Sidney Wolfe, director of the Public Citizens Health Research Group, an offshoot of the Ralph Nader organization. "The drug companies could afford to do orphan drugs and on occasion they have, but no amount of tax credits can deal with this issue." While there is hope for L-5HTP -- Bolar Drugs of Copiague, N.Y., has agreed to sponsor its testing -- Sharon Dobkin still has her doubts: "I'm very pessimistic that will ever see the drug I need being made."

--By Claudia Wallis.

Reported by Anne Constable/Washington

With reporting by Anne Constable/Washington

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