Japan's Ministry of Health, Labour and Welfare has approved Wakix (pitolisant) for two indications: excessive daytime sleepiness (EDS) associated with obstructive sleep apnea syndrome (OSAS) in patients already receiving treatment for airway obstruction, and narcolepsy (type 1 and type 2, with and without cataplexy). Viatris (Nasdaq: VTRS), which holds Japan rights to the drug, said Wakix is the first histamine H3 receptor antagonist/inverse agonist approved in Japan for these indications.
Wakix is administered orally and is not classified as a controlled substance in Japan, where it has received orphan drug designation for narcolepsy. The drug was discovered by France-based Bioprojet and licensed to Viatris for the Japan market following Viatris' acquisition of Aculys Pharma in October 2025, which secured exclusive Japanese commercialization rights. Viatris said the approval was supported by domestic Phase III clinical trials conducted in Japan, alongside multiple international studies in narcolepsy and in OSAS patients experiencing residual EDS despite continuous positive airway pressure (CPAP) therapy. No specific trial identifiers were disclosed in the company's announcement.
Pitolisant acts as an inverse agonist at presynaptic H3 autoreceptors, relieving tonic inhibition on histaminergic neurons and increasing histamine release in the brain. This pro-histaminergic, pro-wakefulness mechanism also secondarily enhances release of acetylcholine, dopamine, and norepinephrine, and is mechanistically distinct from amphetamine-based stimulants currently used in narcolepsy.