The strategy of chiral switches: lessons from the colorful case of zopiclone → eszopiclone insomnia drugs, globally

The eventful saga of insomnia drugs racemic zopiclone to single-enantiomer eszopiclone chiral switches globally is an opportunity to reconsider the scope of the chiral-switches strategy and to analyze the different assessments by the US FDA and the European Medicines Agency (EMA) thereof, including related novel drug designators New Chemical Entity (NCE) and New Active Substance and the lessons thereof. The covered areas are zopiclone and eszopiclone’s events at drug regulatory authorities, including marketing authorizations worldwide and novel drug designations conferring regulatory exclusivities, along with basic and enantiomer patents and litigations thereof. The lessons pertaining to the chiral-switches strategy are: Chiral switches criteria should be restricted to approvals within the relevant jurisdiction. Twisted chiral switches, whereupon components of chiral-switch drugs were patented but the racemic drugs were not approved, should not be considered chiral switches. The EU de facto denial of NAS status to eszopiclone highlights the importance of regulatory exclusivity when patent-exclusivity periods are short. In spite of the chain of events of zopiclone and eszopiclone patents and litigations thereof, the chiral-switches case law was not enriched. The regulatory approvals of eszopiclone in many jurisdictions in the 2020s, many years after zopiclone approvals, confirm the vitality of the chiral-switches strategy.