The Orphan Drug Act of 1983 was passed by Congress to stimulate the development of drugs for rare diseases. At the time, private industry had little motivation to invest money in the development of treatments for small patient populations because these drugs were expected to be unprofitable. The pharmaceutical industry’s increasing interest in the development of therapeutics for orphan diseases can be attributed to the incentives that the law provides. The Office of Orphan Products Development uses clinical superiority to preserve marketing exclusivity, which is 7 years for sponsors. In addition, there is a tax credit incentive for 50 percent of the cost of conducting human clinical trials for products with orphan drug status and there are Federal research grants available for the clinical testing of new therapies treat and diagnose rare diseases. Furthermore, in 1997, Congress granted companies developing products with orphan drug status an exemption from the usual drug application or “user” fees charged by the FDA.
A disease may be classified as an orphan if it is a rare disease, which, according to the US criteria, is one that affects fewer than 200,000 people, or if there is a potential for lack of return on investment (a very difficult case to make with FDA). A disease may also fall into the orphan category if it is a common disease that has been ignored because it is more prevalent in developing countries. To obtain orphan drug status, sponsors must submit an application to the Office of Orphan Products Development and following the submission of the application, a response from the FDA should be given within 60 days of receipt. Life threatening illnesses make marketing applications eligible for faster review and many orphan drug indications treat a serious or a life-threatening disease.
EU orphan designation has its own criteria as well. To qualify for orphan drug status, a medicine must be intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the EU at the time of submission of the designation application. The medicine may also be intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition and without incentives it is unlikely that the revenue after marketing of the medicinal product would cover the investment in its development. In both cases, there must also be either no satisfactory method of diagnosis, prevention or treatment of the condition concerned is authorized, or, if such a method does exists, the medicine must be of significant benefit to those affected by the condition.
At a recent BioPharm America Conference, it was noted that companies are looking to subdivide conditions of more common diseases to capitalize on the advantages afforded by rare diseases. Genetic defects are often times associated with an orphan disease. By finding a genetic cause, there is the potential to define the indication of interest as one that will meet the requirements to be classified as an orphan disease. A precedent for subdividing diseases to create orphan product subsets would increase the opportunities for companies to benefit from the advantages of orphan drug development and marketing approval. It has been proposed that the definition of an orphan drug should expand to include subsets of broad illnesses with an unmet medical need (e.g., patient’s refractory to first line therapy). Approximately 459 million people in the world have a classically defined rare disease. This number of patients would increase dramatically if regulators adopted a less stringent definition of an orphan disease, but perhaps there would be an impact on incentives offered by regulatory agencies.
Do you think the definition of an orphan drug should be expanded?
For more information on Orphan diseases:
The Orphan Drug Act: Implementation and Impact
The Orphan Drug Act