Rare Diseases : Adopting the 'Orphans'

by Food and Drug Administration (FDA)

(Page 2 of 3)

Before the passage of rare disease laws in the United States, patients diagnosed with a rare disease were denied access to effective medicines because prescription drug manufacturers rarely could make a profit from marketing drugs to such small groups. Consequently, the prescription drug industry did not adequately fund research for orphan product development. Other potential sources, such as research hospitals and universities, also lacked the capital and business expertise to develop treatments for small patient groups. Despite the urgent health need for these medicines, they came to be known as "orphans" because companies were not interested in "adopting" them.

This changed in 1983 when Congress passed the Orphan Drug Act (ODA). The ODA created financial incentives for drug and biologics manufacturers, including tax credits for costs of clinical research, government grant funding, assistance for clinical research, and a seven-year period of exclusive marketing given to the first sponsor of an orphan-designated product who obtains market approval from the Food and Drug Administration for the same indication. At the same time, federal programs at the FDA and the NIH began encouraging product development, as well as clinical research for products targeting rare diseases.

Since 1983, the ODA has resulted in the development of nearly 250 orphan drugs, which now are available to treat a potential patient population of more than 12 million Americans. In contrast, the decade prior to 1983 saw fewer than 10 such products developed without government assistance. As a result, treatments are available to people with rare diseases who once had no hope for survival.

In April 2003, for example, the FDA approved the very first treatment for Fabry's disease, a serious metabolic genetic disorder that affects 1 in 40,000 American men. Fabrazyme (agalsidase beta) was approved under an accelerated or early approval policy that allows faster approval of therapies that treat serious or life-threatening illnesses. Accelerated approval can be granted when favorable results in early studies indicate outcomes that are likely to predict long-term clinical benefit.

Fabrazyme, given intravenously, is a version of the human form of a natural enzyme produced by recombinant DNA technology. This replacement of the missing enzyme reduces a particular type of lipid (fat) accumulation in many types of cells, including blood vessels in the kidneys and other organs. It is believed likely that this reduction of fat deposits will prevent the development of life-threatening organ damage and have a positive health effect.

"A key part of our accelerated approval process involves further study of the new treatment after approval to confirm clinical benefit," says Jesse Goodman, M.D., M.P.H., director of the FDA's Center for Biologics Evaluation and Research. "In this case, FDA has worked closely with the product developer to make sure that, despite the relatively small number of patients with this disease, all reasonable steps will be pursued to make sure that we learn more about the product's clinical benefits and long-term safety once it is on the market."

Despite the success of the ODA, however, rare disease advocacy groups argue that the plight of people with orphan diseases deserves even more attention.

The FDA's Role

"A lot of people are affected," says Marlene E. Haffner, M.D., M.P.H., director of the FDA's Office of Orphan Products Development (OOPD). "That makes it a major public health impact, and in time, we're going to see even more rare diseases requiring treatment."

Because of the FDA's desire to find ways to bring orphan drugs to the marketplace, the agency established the OOPD in 1982. Its mission is to identify orphan drugs and biological products and to promote development of those that demonstrate promise for the diagnosis and treatment of rare diseases. The OOPD does this by working with the medical and research communities, professional organizations, academia, and the pharmaceutical industry, as well as rare disease groups.

Each orphan product designation request must stand on its own merit. People need to know that the approval of an orphan designation request does not change the standard regulatory requirements or the process for obtaining marketing approval. That means the product must go through the new drug approval process like any other drug. The safety of a product, and its effectiveness, also must be established through adequate and well-controlled studies.

In addition, the OOPD administers a grants program that funds clinical studies for the development of orphan products. The goal of the program is to encourage clinical development of products for use in rare diseases or conditions. The products studied can be drugs, biologics, medical devices, or medical foods.

About the Author

www.fda.gov
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.