US FDA clears pitolisant for treatment of excessive daytime sleepiness

August 19, 2019 0 By FM

Harmony Biosciences announced that the US FDA approved pitolisant (Wakix) for the treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy.

Pitolisant is the first and only treatment approved for patients with narcolepsy that is not scheduled as a controlled substance by the US Drug Enforcement Administration (DEA), according to the company.

A selective histamine 3 (H3) receptor antagonist/inverse agonist that works through a novel mechanism of action to increase the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain. pitolisant is administered orally once daily in the morning upon wakening.

The efficacy of pitolisant for the treatment of EDS in adult patients with narcolepsy was evaluated in two multicentre, randomised, double-blind, placebo-controlled studies (HARMONY 1 and HARMONY 1bis). These studies included a total of 261 patients who were randomised to receive pitolisant, placebo, or active control; these patients had a median age of 37 (HARMONY 1) and 40 (HARMONY 1bis).
Treatment duration was eight weeks, with a three-week dose titration phase followed by a 5-week stable dose phase; 75% to 80% of the patients in these studies had a history of cataplexy. In both of these studies, the drug demonstrated a statistically significant improvement in EDS as measured by the Epworth Sleepiness Scale (ESS) score.
In the placebo-controlled trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (occurring in =5% of patients and at twice the rate of placebo) with the use of pitolisant were insomnia (6%), nausea (6%), and anxiety (5%).

The drug will be commercially available to healthcare professionals in the US in the fourth quarter of 2019.

Pitolisant was designed and developed by Bioprojet Societe Civile de Recherche (Bioprojet), who has marketed the product in Europe since its approval by the European Medicines Agency in 2016. Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialise pitolisant in the US.

Narcolepsy is a rare, chronic, debilitating neurologic disorder of sleep-wake state instability that impacts up to 200,000 Americans and is primarily characterized by excessive daytime sleepiness (EDS) and cataplexy its two cardinal symptoms along with other manifestations of REM sleep dysregulation, which intrude into wakefulness. EDS is the inability to stay awake and alert during the day and is the symptom that is present in all people living with narcolepsy. In most patients, narcolepsy is caused by the loss of hypocretin, a neuropeptide in the brain that supports sleep-wake state stability. This disorder affects men and women equally, with typical symptom onset in adolescence or young adulthood; however, it can take up to a decade to be properly diagnosed.