Modality diversification and best-in-class small-molecule drugs: Recent trend of orphan drug development

Abstract

Only 5% of orphan diseases have approved drugs, leading to a high demand for new treatment. As a result, pharmaceutical companies have shifted their focus of drug development to orphan diseases. This study conducted a database search to analyze the modality and development strategy of orphan drugs approved by the Food and Drug Administration from 2011 to 2022. The analysis showed that the modalities used for orphan drugs have diversified with increasing emergence of nucleic acid drugs, gene therapies, cell therapies, antibody drugs including next-generation antibodies, and engineered proteins, suggesting that modality diversification enhances the drug development for orphan diseases that are otherwise challenging to treat with conventional drugs. The ratio of orphan drugs targeting only a single disease has increased, likely due to the emergence of gene-specific treatments such as nucleic acid drugs and gene therapies. Moreover, this study found that orphan drugs using different modalities have been competitively developed with the same mechanism of action targeting only a single orphan disease in recent years. In several cases, small-molecule drugs with unique characteristics offer advantages such as dosing convenience and non-genetic patient coverage over nucleic acid drugs, antibody drugs, and gene therapy. These trends suggest the importance of modality technology development and advancement of small molecule optimization technology for future orphan drug development.