Skip to main content
SpringerLink
Log in

Pitolisant: Pediatric First Approval

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

Abstract

Pitolisant (WAKIX®), a histamine H3 receptor antagonist/inverse agonist that has been developed by Bioprojet Pharma, is approved in the EU and USA and elsewhere for use in adults with narcolepsy with or without cataplexy. In February 2023, based on clinical data in patients aged 6 to < 18 years, pitolisant received its first approval in adolescents and children from the age of 6 years for the treatment of narcolepsy with or without cataplexy in the EU. This article summarizes the milestones in the development of pitolisant leading to this pediatric first approval for narcolepsy with or without cataplexy.

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

Access this article

Log in via an institution

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. Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. Eur J Neurol. 2021;28(9):2815–30.

    Article  PubMed  Google Scholar 

  2. Bruni O. Approach to a sleepy child: diagnosis and treatment of excessive daytime sleepiness in children and adolescents. Eur J Paediatr Neurol. 2023;42:97–109.

    Article  PubMed  Google Scholar 

  3. Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895–945.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lin JS, Dauvilliers Y, Arnulf I, et al. An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin−/− mice and patients. Neurobiol Dis. 2008;30(1):74–83.

    Article  PubMed  Google Scholar 

  5. European Medicines Agency. Pitolisant: EU summary of product characteristics. 2023. https://www.ema.europa.eu/. Accessed 11 Apr 2023.

  6. Harmony Biosciences LLC. Pitolisant: US prescribing information. 2022. https://wakix.com/. Accessed 12 Apr 2023.

  7. European Medicines Agency. Wakix (pitolisant). 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/wakix. Accessed 14 Apr 2023.

  8. Harmony Biosciences LLC. Harmony Biosciences announces FDA approval Of WAKIX (pitolisant), a first-in-class medication for the treatment of excessive daytime sleepiness in adult patients with narcolepsy [media release]. 15 Aug 2019. https://www.harmonybiosciences.com/.

  9. Harmony Biosciences LLC. Harmony Biosciences receives FDA approval for expanded use of WAKIX® (pitolisant) for the treatment of cataplexy in adult patients with narcolepsy [media release]. 13 Oct 2020. https://www.harmonybiosciences.com/.

  10. Lamb YN. Pitolisant: a review in narcolepsy with or without cataplexy. CNS Drugs. 2020;34(2):207–18.

    Article  PubMed  Google Scholar 

  11. Endo International plc. Paladin Labs Inc. announces approval of WAKIX® (pitolisant) in Canada [media release]. 9 Jun 2021. https://investor.endo.com/.

  12. European Medicines Agency. Commission implementing decision. 2023. https://www.ema.europa.eu/. Accessed 11 Apr 2023.

  13. Harmony Biosciences LLC. Harmony Biosciences reports second quarter 2022 financial results and business updates [media release]. 2 Aug 2022. https://www.harmonybiosciences.com/.

  14. Harmony Biosciences LLC. Harmony Biosciences acquires US rights to pitolisant from Bioprojet; raises $270 million in equity financing [media release]. 6 Oct 2017. https://www.harmonybiosciences.com/.

  15. Aculys Pharma Inc. Aculys Pharma closes US$60 million Series A financing led by SoftBank Vision Fund 2 [media release]. Oct 28 2021. https://aculys.com/.

  16. Citrine Medicine. Citrine Medicine advances efforts to create the very first rare disease ecosystem in China through strategic partnership with Bioprojet to license exclusive rights for the use of orphan narcolepsy therapy WAKIX® (pitolisant) [media release]. 28 Oct 2020. https://www.prnewswire.com/.

  17. Endo International plc. Bioprojet and Endo jointly announce agreement for Paladin Labs Inc. to commercialize pitolisant in Canada [media release]. 25 Jul 2018. https://investor.endo.com/.

  18. AOP Orphan Pharmaceuticals AG, Bioprojet. AOP Orphan will distribute WAKIX® (pitolisant) from Bioprojet Pharma SAS in Austria, Nordic countries and Central Eastern Europe [media release]. 22 Mar 2018. https://www.aop-health.com/.

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

  20. Rusjan P, Sabioni P, Di Ciano P, et al. Exploring occupancy of the histamine H(3) receptor by pitolisant in humans using PET. Br J Pharmacol. 2020;177(15):3464–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lecendreux M, Plazzi G, Franco P, et al. Pharmacokinetics of pitolisant in children and adolescents with narcolepsy. Sleep Med. 2020;66:220–6.

    Article  PubMed  Google Scholar 

  23. Dauvilliers Y, Lecendreux M, Lammers GJ, et al. Safety and efficacy of pitolisant in children aged 6 years or older with narcolepsy with or without cataplexy: a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2023;22(4):303–11.

    Article  CAS  PubMed  Google Scholar 

  24. Bioprojet. WAKIX® (pitolisant) receives approval for the treatment of narcolepsy in children over 6 years of age, a rare, under-diagnosed condition [media release]. 15 March 2023. https://www.prnewswire.com.

Download references

Author information

Authors and Affiliations

  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Susan J. Keam

Authors
  1. Susan J. Keam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan J. Keam.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

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 authors on the basis of scientific completeness and accuracy. Susan J. Keam is a contracted employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability

Not applicable.

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.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 188 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keam, S.J. Pitolisant: Pediatric First Approval. Pediatr Drugs 25, 483–488 (2023). https://doi.org/10.1007/s40272-023-00575-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-023-00575-w

Search

Navigation