Background Development of drugs in SLE is difficult for many reasons including the heterogeneity of the disease, the outcome measures used to define responsiveness which are cumbersome, poorly responsive to change and have little relationship to clinical practice. The drugs targets are potentially immunosuppressive in an immunologically compromised host. Regulatory agencies require large safety databases associated with the development programs. Consideration of alternate pathways for approval may be warranted. In Europe and the US the Orphan Drug Designation allows for therapies to be approved on far smaller data bases, at typically less cost and patient burden.

Methods In the US, the US FDA requires the disease or condition for which the drug is intended will affect fewer than 2 00 000 people in the United States or, if the drug is a vaccine, diagnostic drug, or preventive drug, the persons to whom the drug will be administered in the United States are fewer than 2 00 000 per year. Alternatively, for a drug intended for diseases or conditions affecting 2 00 000 or more people, or for a vaccine, diagnostic drug, or preventive drug to be administered to 2 00 000 or more persons per year in the United States, there is no reasonable expectation that costs of research and development of the drug for the indication can be recovered by sales of the drug in the United States. In the US, if a sponsor requests orphan-drug designation for a drug for only a subset of persons with a particular disease or condition that otherwise affects 2 00 000 or more people (‘orphan subset’), a demonstration that, due to one or more properties of the drug, the remaining persons with such disease or condition would not be appropriate candidates for use of the drug.

In Europe, the EMA expects that the disease is either life-threatening or debilitating, the medical plausibility of the proposed orphan indication; and importantly, that the prevalence of the condition in the European Union is not more than five in 10,000; or that it is unlikely that marketing the medicinal product in the European Union, without incentives, would generate sufficient return to justify the necessary investment; and furthermore, that no satisfactory method of diagnosis prevention or treatment exists, or if such a method exists, that the medicinal product will be of significant benefit to those affected by the condition.

An example of a prevalence analysis in SLE is shown in table 1.