Rare Diseases: Can We Speed Treatments?

Every orphan — even an orphan disease therapy — needs love and care.

An orphan drug is one that is designed to treat a rare disease, classified as a disease that affects 200,000 or fewer people in the United States.

The National Academies’ Institute of Medicine is preparing a report exploring existing strategies for promoting research and the creation of orphan products to improve the health of people with rare diseases. The report, which will be issued at the end of September 2010, is a response to a request calling for a closer examination of current systems. The request came from the National Institutes of Health’s Office of Rare Diseases Research and the Food and Drug Administration’s Office of Orphan Products Development.

The focus of the report will be guided by suggestions from several health organizations, including BIO, AdvaMed, the Genetic Alliance and PhRMA, which met in the fall to discuss orphan products. Several reasons for the lack of development of orphan and pediatric drugs, including difficulty setting up clinical trials as required by the FDA, were discussed at the meeting and in follow-up responses.

Susan Alpert, senior vice president of global regulatory affairs for Medtronic, says the reduced sample sizes in orphan product trials when seeking FDA approval must be taken into consideration.

“FDA must develop regulatory models and adaptive clinical designs,” Alpert say. She suggests that the agency permit more-general claims, which would allow for device approval. Because the number of people for some orphan products is small and often dispersed, it can be difficult to gather the required number of trial participants, she points out.

Special Considerations

The AdvaMed response also notes the importance of prioritizing orphan and pediatric product needs, “based on criteria such as size of patient population, public health need, and commercialization potential.” Whether a product can treat more than one type of ailment should also be taken into account, Alpert says.

BIO agrees, says Sara Radcliffe, acting executive vice president for health. “The regulatory approval pathway simply must be more predictable,” she says. Radcliffe also notes that the FDA had previously committed to “developing a series of guidances regarding clinical trial design; adaptive clinical trials; and new methods of statistical analysis.” Such guidance would be useful for orphan drug development, she says, adding that the FDA has yet to publish this information.

To speed up the approval of orphan and pediatric products, Alpert also recommends allowing for the extrapolation of clinical data for varying sizes of devices based on engineer testing or other nonclinical data.

“It can be difficult to assemble enough patients at either end of the size ranges to be valid,” she says. “It is often extremely challenging to get significant data on the smallest and largest sizes.”

Another option would be to expand reimbursement of on-label orphan drugs from insurers to certain off-label used drugs.

“The lack of reimbursement often impedes access to these products and, in turn, provides a disincentive for companies to develop them,” Radcliffe says. To solve this, BIO suggests creating a list of acceptable off-label orphan drugs, similar to the practice used for certain cancer drugs.

“To get listed in a compendium, the manufacturer must provide data regarding safety and effectiveness of its product for the off-label indication,” Radcliffe says. This system would “allow patients suffering from rare diseases timely access to new therapies and encourage innovation.”

Many of the participants feel the most important step toward awareness and increased development of orphan drugs is collaboration among all stakeholders, including biotech and biopharmaceutical companies and key lawmakers.

Sharon Terry, president and CEO of the Genetic Alliance, says collaborative efforts by NIH, the FDA and industry would increase the creation and approval of orphan products. She suggests the formation of more public-private partnerships and a registry network for products that would be accessible to all stakeholders.