Wakix (pitolisant) / Bioprojet, Ferrer International, Paragon Biosci, RareStone Group, Aculys Pharma - LARVOL DELTA

Antiseizure Medications that Did Not Reach the Epilepsy Market: An Assessment of Factors Contributing to Their Failed Clinical Development Over the Last Three Decades. (PubMed, Drugs) - "Compounds whose development was terminated include atimepazole, beprodone, cannabidivarin, carabersat, conantokin-G, dezinamide, elpetrigine, flunarizine, fluorofelbamate, ICA-105665, isovaleramide, JNJ-40411813, losigamone, naluzotan, padsevonil, pitolisant, ralitoline, remacemide, safinamide, soretolide, talampanel, tonabersat, T2000, T2007, valnoctamide, valrocemide, VX-765, zandatrigine, zuranolone, and 534U87. In some instances, failure to pursue an epilepsy indication could be explained by prioritization of development for other neurological or psychiatric conditions. This may reflect the perception of the drug market for common epilepsies being relatively crowded, and only attractive for compounds with outstanding safety or efficacy advantages over existing medications."

Journal • Review • CNS Disorders • Epilepsy • Psychiatry

TREATMENT PATTERNS AMONG PEOPLE NEWLY DIAGNOSED WITH NARCOLEPSY TYPE 1 IN THE UNITED STATES: A REAL-WORLD DATA STUDY (ISPOR 2026) - "Within 12 months of diagnosis, 87.2% (506/580) received narcolepsy-related treatments (NRTs: stimulants, antidepressants) or narcolepsy-indicated treatments (NITs: sodium oxybate, pitolisant, modafinil, armodafinil, and solriamfetol); 12.8% remained untreated. Findings indicate that treatment initiation is delayed after NT1 diagnosis, with frequent polypharmacy, switching, and high discontinuation rates within 12 months of diagnosis, highlighting substantial unmet treatment needs and the necessity for newer treatment options."

Clinical • Real-world • Real-world evidence • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Bioprojet | N=60 ➔ 96

Enrollment change • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Bioprojet | Trial primary completion date: Apr 2017 ➔ Dec 2017

Trial primary completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Bioprojet | Trial completion date: Dec 2018 ➔ Dec 2019 | Trial primary completion date: Dec 2017 ➔ Dec 2019

Trial completion date • Trial primary completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Bioprojet | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Bioprojet

New P2 trial • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P3 | N=110 | Completed | Sponsor: Bioprojet | Active, not recruiting ➔ Completed | Trial completion date: Mar 2025 ➔ Jun 2025

Trial completion • Trial completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Bioprojet | Trial completion date: Oct 2024 ➔ Mar 2025

Trial completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Bioprojet | Trial completion date: Dec 2023 ➔ Oct 2024

Trial completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Bioprojet | Trial completion date: Sep 2022 ➔ Dec 2023

Trial completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Bioprojet | Trial completion date: Nov 2021 ➔ Sep 2022

Trial completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P3 | N=97 | Active, not recruiting | Sponsor: Bioprojet | Phase classification: P2 ➔ P3 | Trial completion date: Oct 2020 ➔ Nov 2021 | Trial primary completion date: Oct 2020 ➔ Apr 2021

Phase classification • Trial completion date • Trial primary completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period (clinicaltrials.gov) - P2 | N=97 | Active, not recruiting | Sponsor: Bioprojet | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2019 ➔ Oct 2020 | Trial primary completion date: Dec 2019 ➔ Oct 2020

Enrollment closed • Trial completion date • Trial primary completion date • Cataplexy • Narcolepsy • Pediatrics • Sleep Disorder

Therapeutic potential of histamine N-methyltransferase inhibition for the treatment of hypersomnia (PubMed, Nihon Yakurigaku Zasshi) - "Compared with pitolisant, an H3 receptor inverse agonist that has been approved in EU and US for treatment of narcolepsy, metoprine exhibited stronger and more sustained wake-promoting effects...Therefore, HNMT inhibitors may represent a novel and effective therapeutic approach for hypersomnia. To further advance drug development, we have performed high-throughput screening based on mass spectrometry, through which approximately 1,000 hit compounds have been identified."

Journal • Cataplexy • CNS Disorders • Movement Disorders • Narcolepsy • Parkinson's Disease • Sleep Disorder

Samelisant (SUVN-G3031), a histamine H3 receptor inverse agonist, as a potential treatment for narcolepsy: a phase-2 Drug evaluation. (PubMed, Expert Opin Investig Drugs) - "This is particularly important for women of childbearing potential, considering the known interactions of current treatments (e.g. pitolisant and modafinil) with hormonal contraceptives, as well as the common occurrence of polypharmacy and comorbidities in narcolepsy. Additionally, as samelisant may act downstream of orexinergic pathways, it presents an opportunity to complement orexin-based therapies. The potential of samelisant in combination with other narcolepsy treatments represents an important area for future research."

Journal • P2 data • Review • Cardiovascular • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Harmony Biosciences...announced that the U.S. Food and Drug Administration (FDA) has approved its supplemental new drug application (sNDA) for WAKIX (pitolisant) tablets for the treatment of cataplexy in pediatric patients 6 years of age and older with narcolepsy. (Businesswire)

FDA approval • Cataplexy • Narcolepsy

Pharmacological modulation of wakefulness and extracellular hypothalamic histamine release in adult male mice using TAK-925, modafinil, pitolisant, MK-8133 and Lu AF11167. (PubMed, Neuropharmacology) - "In vehicle-treated male mice, histamine levels were correlated with wakefulness but in pharmacologically treated male mice, this correlation was decoupled. These data demonstrate that wake can be modulated without modulating histamine signaling and vice versa."

Journal • Preclinical

Pitolisant-associated mania - a case report. (PubMed, BMC Neurol) - No abstract available

Journal • Bipolar Disorder • CNS Disorders • Mood Disorders • Narcolepsy • Sleep Disorder

Rational Design, Synthesis and Pharmacological Evaluation of Chalcones as Dual-Acting Compounds-Histamine H3 Receptor Ligands and MAO-B Inhibitors. (PubMed, Int J Mol Sci) - "Additionally, for H3R ligands (15, DL76, pitolisant), the study reports the first use of Surface Plasmon Resonance Microscopy (SPRM) to assess their interactions with this receptor. Therefore, piperidinyl chalcones show promise as ligands with dual action on H3R and MAO-B, useful in the treatment of neurodegeneration and/or CNS cancers."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Oncology

A real-world study on the treatment of pediatric narcolepsy with pitolisant in China. (PubMed, Neurol Sci) - No abstract available

Journal • Real-world evidence • Narcolepsy • Pediatrics • Sleep Disorder

Pitolisant Inhibits Alcohol Drinking and Improves Withdrawal Negative Affect Through Lateral Habenula Histaminergic Signaling in Mice. (PubMed, CNS Neurosci Ther) - "These findings highlight the HAergic system as a critical regulator of alcohol-related behaviors. The LHb HA signaling and norepinephrine neurotransmission might underlie pitolisant's potential novel therapeutic strategy for AUD."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders • Psychiatry

Pitolisant Improves Depressive Symptoms in CPAP-Treated Patients with Obstructive Sleep Apnea and Severe Residual Sleepiness: First 12-Month Clinical Experience. (PubMed, CNS Drugs) - No abstract available

Journal • CNS Disorders • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

A Study of HBS-201 (Pitolisant Delayed-release) (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Harmony Biosciences Management, Inc. | Recruiting ➔ Completed

Trial completion • Narcolepsy • Sleep Disorder

A Long-Term Safety and Effectiveness Study to Evaluate Pitolisant in Adult Patients With Idiopathic Hypersomnia (clinicaltrials.gov) - P3 | N=119 | Completed | Sponsor: Harmony Biosciences Management, Inc. | Active, not recruiting ➔ Completed

Trial completion • Excessive Daytime Sleepiness • Sleep Disorder