Orphan Drug Designation and Pharmacogenomics

Abstract

The rapid increase in characterization and understanding of the human genome has had a major impact on the development of therapies for rare diseases. The “inborn errors of metabolism”, which are generally rare diseases, are beginning to realize new therapies based on an understanding of disease processes at the genetic level. Likewise, an understanding of acquired genetic errors, as seen in cancer, is allowing for targeted approaches to therapy that are revolutionizing, in many cases, both standards of care and prognosis. Since its inception, the Office of Orphan Products Development has been privileged to witness many of the successes and also the failures of pharmacogenomics as it relates to rare diseases. This approach, from a regulatory standpoint, often calls into question even basic assumptions about disease classification. Phenotypically homogeneous diseases are more frequently becoming ‘subsetted’ on the basis of genomics; conversely, overlap of therapeutic mechanisms of action is increasingly seen across seemingly diverse diseases. With the recent completion of sequencing of the human genome, as well as the increasing ease of DNA sequencing, the promise and challenge of the pharmacogenetic approach to treatment will be expected to play an increasingly important role in development of new therapies for both rare and common diseases.