In short
Pitolisant hydrochloride is a histamine H3 receptor antagonist and inverse agonist that is already authorised as a medicine under the trade name Wakix for treating narcolepsy and excessive daytime sleepiness caused by obstructive sleep apnoea. It is now being investigated in Prader-Willi syndrome, with one Phase 3 clinical trial currently authorised in the EU registry.
Key points
- Pitolisant hydrochloride is an authorised medicine sold as Wakix and also studied under the development code HBS-101.
- It acts as a histamine H3 receptor antagonist and inverse agonist, which increases histamine release in the brain.
- The authorised uses are narcolepsy and excessive daytime sleepiness caused by obstructive sleep apnoea.
- One Phase 3 trial is now authorised to study pitolisant in Prader-Willi syndrome.
- The Prader-Willi trial plans to enrol 134 participants and is currently in the Authorised status.
- The main measure is the change in excessive daytime sleepiness severity from baseline to day 77.
What is pitolisant hydrochloride?
Pitolisant hydrochloride is a histamine H3 receptor antagonist and inverse agonist. It is also known by the development code HBS-101 and the trade name Wakix. The substance is classified under the ATC code N07XX11, which places it among other nervous system drugs. Pitolisant is already an authorised medicine: the NHS dm+d browser lists pitolisant 18 mg tablets as a valid prescribable product, and the North East and North Cumbria formulary records Wakix as approved for use in patients with narcolepsy who experience psychomotor side effects with modafinil and dexamfetamine. The formulary also links NICE technology appraisal TA776, which covers pitolisant hydrochloride for treating excessive daytime sleepiness caused by obstructive sleep apnoea.
How does pitolisant hydrochloride work?
Pitolisant blocks the histamine H3 receptor and acts as an inverse agonist at that receptor. The H3 receptor normally works as a brake on histamine release in the brain; by blocking it, pitolisant increases the availability of histamine, a neurotransmitter that promotes wakefulness. A positron emission tomography (PET) study in humans explored how much of the histamine H3 receptor is occupied by pitolisant, providing direct evidence of its target binding in the brain.
Which conditions is it used or studied for?
- Narcolepsy — an authorised use; pitolisant is approved for treating narcolepsy with or without cataplexy in adults.
- Excessive daytime sleepiness caused by obstructive sleep apnoea — an authorised use covered by NICE technology appraisal TA776.
- Prader-Willi syndrome — a rare genetic condition currently being investigated in a Phase 3 trial of pitolisant.
How is pitolisant hydrochloride given?
Pitolisant is given by mouth as a film-coated tablet. The NHS dm+d browser records pitolisant 18 mg tablets, and the trade name Wakix 18 mg tablets is listed as an actual medicinal product. In the Prader-Willi syndrome trial, the studied dose is 44.5 mg given orally, with matching placebo tablets of 4.45 mg and 17.8 mg also described.
What do the clinical trials show?
The EU Clinical Trials Information System lists one clinical trial investigating pitolisant in Prader-Willi syndrome. This is a Phase 3 efficacy and safety study with a planned enrolment of 134 patients. The trial is currently in the Authorised status, meaning it has received regulatory approval to begin.
The primary outcome measure is the change in severity of excessive daytime sleepiness (EDS) as measured by the PROMIS SRI T-score from baseline to the end of the double-blind treatment period on day 77. The PROMIS SRI is a patient-reported questionnaire that captures how sleepy a person feels in everyday situations; a T-score is a standardised way of expressing that score. The trial compares pitolisant (given as HBS-101 or Wakix, both at 44.5 mg orally) against matching placebo tablets.
What side effects are known?
The North East and North Cumbria formulary notes that pitolisant is approved for use in patients with narcolepsy who experience psychomotor side effects with modafinil and dexamfetamine, which indicates that pitolisant is used when other treatments cause troublesome side effects. The sources provided do not list a separate side-effect profile for pitolisant itself.
Frequently asked questions
The questions below cover the main points patients ask about pitolisant hydrochloride.