At a time when the public seems terminally pessimistic that pharma regulation promotes the public good, it's reassuring to
look back at a canny piece of legislation that for a quarter century has been doing just what it was intended to do.
The law in question is the Orphan Drug Act of 1983, sponsored by Rep. Henry Waxman (D-CA). Back then, pharmaceutical companies
were unlikely to invest in developing drugs for rare diseases—FDA had approved only 10 in the preceding decade. But Waxman's
act offered some powerful economic incentives for orphan development, including seven years of exclusivity that blocks other
companies from selling the same drug to treat the same disease, a 50 percent tax credit for clinical study costs, grants to
support clinical research, and FDA protocol assistance. In 1985, further legislation added biologics to the program, and defined
orphan drugs as treatments for diseases affecting fewer than 200,000 Americans.
The ODA has demonstrated that economic incentives and regulatory flexibility can spur development of previously discarded
treatments for small patient populations. Since enactment, FDA has approved more than 300 medicines for some 12 million patients
around the world. Today, genomic discoveries have the potential to expand our understanding of the science behind many serious
conditions, and personalized medicine promises increased benefits and decreased side effects for many therapies, commented
Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER) at a May conference sponsored by the Drug Information
Association (DIA). Still, there are some 6,000 to 8,000 rare diseases, notes Woodcock, and "we still have a very long way
The incentives for industry contained in the ODA have generated some controversy, however. Certain orphan therapies such as
human growth hormone became highly profitable, raising cries about limiting exclusivity and preventing "salami slicing"—seeking
orphan status for a very narrow indication with an eye to promoting the drug more broadly after approval. In addition, high
prices for certain orphan therapies have led to challenges for payers, and limited patient access to vital medicines.
The ODA gave FDA the job of defining orphan diseases and potential treatments. In the last 25 years, FDA's Office of Orphan
Products Development (OOPD) has received 2,622 requests for orphan designations, and has awarded that status to 1,850 products.
Of those, 326 have been approved, and 41 of those orphan drugs were supported by FDA grants.
Seeking Tropical Disease Treatments
After OOPD designates an orphan product, it's up to CDER's new-drug review offices to evaluate clinical protocols and approve
market applications (as with any new medical product). Review staffs vary in how willing they are to modify data requirements
to accommodate treatments for small patient populations. OOPD doesn't "meddle" in safety and efficacy assessments, notes OOPD
chief Timothy Coté, but his office does provide input requested by review divisions, and works to prevent reviewers from rejecting
products that might have modest benefit.
Russell Katz, director of CDER's Division of Neurology Products, says that reviewers try to be flexible about orphan drugs,
especially when no other therapy is available. He explains that randomized withdrawal studies and trial enrichment strategies
can be useful for testing orphan drugs, but trials must have some minimum number of patients to justify the study. "The last
thing a sponsor wants is to invest in a study that's fated to fail because it does not have enough patients," says Katz.