Interim analysis of a post-authorization safety study of pitolisant in treating narcolepsy: A real-world European study
- PMID: 39978240
- DOI: 10.1016/j.sleep.2025.02.012
Interim analysis of a post-authorization safety study of pitolisant in treating narcolepsy: A real-world European study
Abstract
Background: Narcolepsy is a chronic sleep disorder characterized mainly by excessive daytime sleepiness (EDS) and cataplexy in the case of narcolepsy type 1 (NT1). Pitolisant is a histamine 3 receptor antagonist/inverse agonist that reduces EDS and cataplexy in patients with narcolepsy.
Methods: We performed a prospective 5-year follow-up, non-interventional study of adults with NT1 and NT2 receiving pitolisant. The primary objectives were to collect information on the long-term safety of pitolisant and analyze the utilization patterns of pitolisant. The secondary objectives were to assess clinical benefit, adherence, impact on patients' quality of life, disease burden, and patient satisfaction. We reported the results of an interim analysis after 42.6 months.
Results: The population comprised 370 patients (mean age, 40 ± 15 years; 51.4 % women; NT1, 71.4 %; NT2, 28.6 %); 364 received ≥1 dose of pitolisant. Data were available for 356 patients (97.8 %). Most patients (68.4 %) had ≥1 comorbidity (obesity [BMI≥30], 31.9 %; neuropsychiatric, 31 %; and cardiovascular, 22.8 %). Forty-eight patients (13.2 %) had received no prior narcoleptic treatment, while 98 (31 %) were taking a previous therapy, which was switched to pitolisant. Treatment was combined with pitolisant in 218 (69 %) patients. Pitolisant was discontinued by 131 patients (35.4 %), mainly for safety reasons (14.3 %), lack of response (8.7 %), and patient decision (7.6 %). Overall, 355 treatment-emergent adverse events (3 serious) were reported by 156 patients (42.9 % of safety population), with 218 possibly treatment-related (61.4 %) in 109 patients (29.9 %). Improvements were observed in EDS, cataplexy, and quality of life.
Conclusions: Pitolisant was generally safe and well tolerated in patients with NT1 and NT2 and can be used in both types. Improvements were found in EDS, cataplexy, and quality of life, with good adherence and satisfaction.
Keywords: Efficacy; Europe; Narcolepsy; Pitolisant; Safety.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Plazzi serves on advisory boards for Bioprojet Pharma, Takeda Pharma, Idorsia, Orexia/Centessa, and Jazz Pharmaceuticals. Geert Mayer has received honoraria for participating on advisory boards from Bioprojet Pharma. Alessandro Cicolin has been involved in clinical trials, scientific work, consulting, conferences, symposiums, and other activities over the past 5 years for the following companies and organizations: Idorsia, Jazz, Bioprojet, Fidia Pharma, Sapio Life, MedicAir, and Viatris. Luigi Ferini Strambi declares conflict/s of interest for PI in clinical trials and/or Advisory Board and/or speaker: Italfarmaco, Pfizer, Philips Respironics, Angelini ACRAF, Bioprojet, Lundbeck, Jazz Pharma, Sanofi, MSD, EISAI, Rottapharm. Peter Geisler has received speaker's honoraria from Bioprojet Deutschland GmbH. Anna Heidbreder received fees for lectures and participating on advisory boards from Idorsia, Bioprojet, Inspire, and Vanda. Jürgen Herold has received lecture fees from Astra Zeneca, Sanofi, Boehringer Ingelheim, Chiesi, Berlin Chemie, Löwenstein Medical, ResMed, HMP Hans Müller u. Partner Medizintechnik, Inspire; and has participated in clinical studies for Bioproject, Nyxoah, Inspire, Berlin Chemie, Astra Zeneca. Ulf Kallweit serves on advisory boards for Bioprojet Pharma and Takeda Pharma. He is also a consultant to AOP Orphan Pharmaceuticals, Bioprojet Pharma, Jazz Pharmaceuticals, Pharmanovia, and Takeda Pharma and has accepted institutional grants/research support from Bioprojet Pharma, Jazz Pharmaceuticals, and Harmony Biosciences. Laurène Leclair-Visonneau has been invited to congresses by UCB Pharma and Bioprojet Pharma and has received speaker's honoraria from AbbVie and grants for research support from UCB Pharma (2019). Claudio Liguori has received research support and/or consultancy fees and/or participated on advisory boards for Altais Pharma, Bioprojet, and Jazz Pharmaceuticals. Liborio Parrino has provided consultancy for Idorsia. Monica Puligheddu has served on scientific advisory boards for Angelini, Eisai, GW/Jazz, UCB Pharma, Idorsia, Bioproject, and Livanova. She has served on speakers' bureaus for or has received unrestricted grants from Angelini, Eisai, Pfizer, UCB Pharma, Idorsia, Livanova, Bioprojet, Fidia, and Viatris. Jan Remi has received speaker's honoraria from Angelini, AstraZeneca, Bioprojet, Desitin, Eisai, Hennig Pharma, Jazz, UCB, and VANDA. Andrea Romigi reports consultancy fees from Bioprojet, Idorsia, Eisai, and Fidia. Sven Rupprecht has received research support from Heel, travel grants and speaker's honoraria from Bioprojet, Idorsia, and Vanda not related to the study. Yaroslav Winter reports honoraria for educational presentations and consultations from Angelini Pharma, Axsome Therapeutics, Avextra Pharma, Bayer AG, BIAL, Bioprojet, Bristol Myers Squibb, Eisai, Idorsia Pharmaceuticals, JAZZ Pharmaceuticals, LivaNova, Novartis, and UCB Pharma. Christian Caussé is an employee of Bioprojet Pharma. Irène Collin is an employee of Bioprojet Pharma. Isabelle Lecomte is an employee of Bioprojet Pharma. Yves Dauvilliers is a consultant for and has participated on advisory boards for Jazz Pharmaceuticals, Avadel, Idorsia, Takeda, Centessa, Harmony Biosciences, and Bioprojet. All other authors declare no conflicts of interest.