Pitolisant (Wakix™) is an inverse agonist of the histamine H3 receptor that is 
being developed by Bioproject. Oral pitolisant is approved in the EU for the 
treatment of narcolepsy with or without cataplexy in adults. Pitolisant has 
received a Temporary Authorization of Use in France for this indication in case 
of treatment failure, intolerance or contraindication to currently available 
treatment. Pitolisant has orphan drug designation in the EU and the USA. In the 
pivotal HARMONY I trial, pitolisant significantly decreased excessive daytime 
sleepiness versus placebo in adults with narcolepsy with or without cataplexy 
(primary endpoint). Pitolisant also significantly decreased cataplexy rate 
versus placebo in these patients. This article summarizes the milestones in the 
development of pitolisant leading to this first approval for narcolepsy.