The Discovery of Suvorexant: Lessons Learned That Can Be Applied to Other CNS Drug Development Efforts.

The development of therapeutics for central nervous system (CNS) disorders has many challenges that result in low probability of success and longer-than-typical development timelines. Suvorexant (Belsomra), the first dual orexin receptor antagonist used for insomnia, was approved by the United States Food and Drug Administration ∼10 years after the initial high-throughput screen was conducted to identify orexin receptor antagonists. What accounted for this success and speed? Here we suggest that this program was unique and set up for success by (1) having a robust and high-throughput pharmacodynamic readout that was translatable across species, including humans, (2) a well-validated target with a defined product profile, resulting in a highly energized team with a can-do attitude, and (3) a highly executable and streamlined clinical strategy. The utility of Belsomra for insomnia, as well as other neurological and psychiatric diseases, continues to be explored, most recently for insomnia associated with Alzheimer's disease.