Skip to main content
Log in

Pitolisant: First Global Approval

  • AdisInsight Report
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schwartz JC. The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol. 2011;163(4):713–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007;369(9560):499–511.

    Article  PubMed  Google Scholar 

  3. Nishino S, Ripley B, Overeem S, et al. Hypocretin (orexin) deficiency in human narcolepsy. Lancet. 2000;355(9197):39–40.

    Article  CAS  PubMed  Google Scholar 

  4. European Medicines Agency. Wakix (pitolisant): summary of product characteristics. 2016. http://www.ema.europe.eu. Accessed 13 Jun 2016.

  5. French National Agency for Medicines and Health Products Safety. WAKIX 20 mg, comprimé pelliculé quadrisécable [media release]. 2014. http://ansm.sante.fr.

  6. European Medicines Agency. Public summary of positive opinion for orphan designation of 1-{3-[3-(4 chlorophenyl)propoxy]propyl}piperidine, hydrochloride for the treatment of narcolepsy. 2010. http://www.ema.europa.eu. Accessed 14 Jun 2016.

  7. Search orphan drug designations and approvals [database on the Internet] [cited 29 Jan]. Available from: http://www.fda.gov.

  8. Schwartz JC. Clinical trials with pitolisant (WAKIX) a wake-promoting H3-receptor inverse agonist [abstract no. L1]. Inflamm Res. 2014;63(Suppl 1):S8.

    Google Scholar 

  9. Collart Dutilleul P, Ryvlin P, Kahane P, et al. Exploratory phase II trial to evaluate the safety and the antiepileptic effect of eitolisant (BF2.649) in refractory partial seizures, given as adjunctive treatment during 3 months. Clin Neuropharmacol. 2016. doi:10.1097/WNF.0000000000000159.

  10. Alium Medical Limited. Alium Medical announces exclusive distribution rights for narcolepsy innovative product Wakix (pitolisant) [media release]. 22 Sep 2014. http://www.samedanltd.com.

  11. Ligneau X, Perrin D, Landais L, et al. BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: preclinical pharmacology. J Pharmacol Exp Ther. 2007;320(1):365–75.

    Article  CAS  PubMed  Google Scholar 

  12. Lin JS, Dauvilliers Y, Arnulf I, et al. An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: studies in orexin−/− mice and patients. Neurobiol Dis. 2008;30(1):74–83.

    Article  PubMed  Google Scholar 

  13. Uguen M, Perrin D, Belliard S, et al. Preclinical evaluation of the abuse potential of pitolisant, a histamine H3 receptor inverse agonist/antagonist compared with modafinil. Br J Pharmacol. 2013;169(3):632–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Leu-Semenescu S, Nittur N, Golmard JL, et al. Effects of pitolisant, a histamine H3 inverse agonist, in drug-resistant idiopathic and symptomatic hypersomnia: a chart review. Sleep Med. 2014;15(6):681–7.

    Article  PubMed  Google Scholar 

  15. Dauvilliers Y, Bassetti C, Lammers GJ, et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol. 2013;12(11):1068–75.

    Article  CAS  PubMed  Google Scholar 

  16. Inocente C, Arnulf I, Bastuji H, et al. Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness. Clin Neuropharmacol. 2012;35(2):55–60.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yahiya Y. Syed.

Ethics declarations

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Yahiya Syed is a salaried employee of Adis, Springer SBM.

Additional information

This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Syed, Y.Y. Pitolisant: First Global Approval. Drugs 76, 1313–1318 (2016). https://doi.org/10.1007/s40265-016-0620-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-016-0620-1

Keywords

Navigation