Abstract
There is a pressing need for new medicines (new molecular entities; NMEs) for rare diseases as few of the 6800 rare diseases (according to the NIH) have approved treatments. Drug discovery strategies for the 102 orphan NMEs approved by the US FDA between 1999 and 2012 were analyzed to learn from past success: 46 NMEs were first in class; 51 were followers; and five were imaging agents. First-in-class medicines were discovered with phenotypic assays (15), target-based approaches (12) and biologic strategies (18). Identification of genetic causes in areas with more basic and translational research such as cancer and in-born errors in metabolism contributed to success regardless of discovery strategy. In conclusion, greater knowledge increases the chance of success and empirical solutions can be effective when knowledge is incomplete.
Acknowledgements
During the review of this manuscript, Dr Shuangluo Xia passed away. Dr Xia was an invaluable colleague and friend to many. He made many significant scientific contributions during his highly productive career and will be deeply missed.
Financial & competing interests disclosure
The authors were employed by the nonprofit Institute for Rare and Neglected Diseases Drug Discovery and partially supported by NIH grant RO1-AI103476. DC Swinney has also consulted or received honoraria for lectures from GSK and Vertex. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.