pitolisant / Generic mfg. - LARVOL DELTA

A longitudinal case report illustrating diagnostic complexity among overlapping sleep-wake phenotypes. (PubMed, Sleep Med) - "Positive airway pressure therapy successfully treated sleep disordered breathing while pitolisant and solriamfetol produced the most durable improvement in daytime sleepiness. Together melatonin plus clonazepam reduced parasomnia frequency and severity. Several other agents (including prazosin, sodium oxybate, paroxetine, and modafinil) were tried and discontinued for limited benefit or adverse effects...The observation may justify further study of metabolic and incretin-related pathways in sleep-related eating behaviors. Overall, this case highlights the complexity of overlapping sleep-wake disorders, the need for individualized pharmacologic sequencing, and a potential emerging role for GLP-1 agonists in SRED."

Journal • CNS Disorders • Delayed Sleep Phase Disorder • Excessive Daytime Sleepiness • Genetic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Sleep Wake Cycle Disorder

Real-world efficacy of pitolisant on residual Excessive Daytime Sleepiness and fatigue in OSAS patients treated with CPAP (ERS 2026) - "Exploratory analyses showed no significant response differences regarding sex, obesity, OSAS severity, age or dose.ConclusionsPitolisant was associated with improved sleepiness, reduced fatigue, and increased CPAP use in OSAS patients with residual EDS. Despite the small sample, these real-world findings support pitolisant as an add-on; larger multicentre studies with objective measures are needed to confirm efficacy and identify predictors."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Excessive Daytime Sleepiness • Fatigue • Genetic Disorders • Obesity • Respiratory Diseases • Sleep Apnea • Sleep Disorder

PITOLISANT FOR RESIDUAL EXCESSIVE DAYTIME SLEEPINESS (EDS) IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA TREATED WITH OVERNIGHT POSITIVE AIRWAY PRESSURE (PAP) THERAPY (ERS 2026) - "Fatigue and insomnia scores also improved. CONCLUSIONPitolisant was effective and well tolerated in managing residual EDS in PAP-treated OSA patients, with meaningful improvement in daytime alertness."

Clinical • Excessive Daytime Sleepiness • Insomnia • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Viatris Announces Approval of WAKIX (Pitolisant) in Japan, a First-in-Class Treatment for Narcolepsy and Excessive Daytime Sleepiness Associated With Obstructive Sleep Apnea Syndrome (Yahoo Finance) - "The approval of Viatris' WAKIX was supported by positive data from domestic Phase 3 clinical trials in Japan as well as multiple international clinical studies evaluating WAKIX in patients with narcolepsy and patients with OSAS experiencing EDS despite treatment with continuous positive airway pressure (CPAP) therapy."

Japan approval • Excessive Daytime Sleepiness in Narcolepsy • Obstructive Sleep Apnea • Sleep Disorder

A Study of Pitolisant in Patients With Prader-Willi Syndrome (clinicaltrials.gov) - P3 | N=134 | Recruiting | Sponsor: Harmony Biosciences Management, Inc. | Trial completion date: Jul 2027 ➔ Apr 2028 | Trial primary completion date: Jul 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Prader–Willi syndrome

Exploration of the therapeutic potential of the HRH3 histamine receptor in MECP2-related disorders. (PubMed, Neuropharmacology) - "We then evaluated both a small molecule agonist of the H3 receptor, (R)-α-methylhistamine (RAMH), and the H3 receptor inverse agonist, pitolisant (Wakix®), in RTT and MDS models, respectively, to determine impacts on phenotypes in these disease models. Our results show little to no efficacy in RAMH or pitolisant in modulating behavioral responses in either mouse line."

Journal • Developmental Disorders • Movement Disorders

Pharmacotherapy in obstructive sleep apnoea: a clinical guide. (PubMed, Sleep Breath) - "This review provides a practical, endotype-aligned summary of pharmacologic options for the management of OSA."

Journal • Review • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Global pharma major Lupin Limited (Lupin) today announced that it has received the final approval from the United States Food and Drug Administration (U.S. FDA) for its Abbreviated New Drug Application for Pitolisant Tablets, 4.45 mg and 17.8 mg. (Lupin Pharmaceuticals Press Release) - "The U.S. FDA has approved Lupin’s Pitolisant Tablets, 4.45 mg and 17.8 mg, as bioequivalent to Wakix for the indications in the approved labeling."

ANDA • CNS Disorders • Excessive Daytime Sleepiness in Narcolepsy • Obstructive Sleep Apnea

Recent Advances and Emerging Pharmacotherapeutic Approaches for Central Hypersomnolence Disorders. (PubMed, Clin Pharmacol) - "In addition, oveporexton, an orexin receptor 2 agonist (OX2R) will be discussed as it marks an important first step in directly counteracting the pathology behind narcolepsy with cataplexy and has completed Phase 2 trials with Phase 3 underway. Early clinical data is promising; however, its long term efficacy and safety data is insufficient to garner US Food & Drug Administration approval, though additional trials are ongoing in narcolepsy with cataplexy, and non-orexin deficient central hypersomnolence disorders as well. Regardless, new drug developments may lead expanded treatment options and may have the potential to decrease or potentially eliminate the need for polypharmacy in the treatment algorithm for narcolepsy and idiopathic hypersomnia."

Journal • Review • Cataplexy • CNS Disorders • Narcolepsy • Psychiatry • Sleep Disorder

Discovery of novel H3R antagonists with potent antiseizure activity and favorable pharmacokinetics via scaffold-hopping from pitolisant to rigid 4-phenylindoles. (PubMed, Bioorg Chem) - "In the zebrafish pentylenetetrazol model, compound 3n reduced locomotor activity by 98.66% at 10 μM, superior to pitolisant (97.49%) and the classic antiseizure drug carbamazepine (58.47%). Molecular docking revealed that compound 3n engaged H3R through a distinct hydrogen bond and π-interaction network. These results support compound 3n as a promising antiseizure candidate."

Journal • PK/PD data • CNS Disorders • Epilepsy

Current and Emerging Therapies for Pediatric Sleep Disorders: A Narrative Review. (PubMed, Neurol Ther) - "Narcolepsy requires a combination of behavioral and pharmacological management, with scheduled naps as first-line therapy and medications such as stimulants, sodium oxybate, and pitolisant targeting excessive daytime sleepiness and cataplexy...Overall, the treatment of pediatric sleep disorders requires a multidisciplinary, individualized approach that integrates behavioral, pharmacologic, and interventional therapies. Advances in precision medicine, device-based treatments, and targeted interventions are expanding the therapeutic landscape, emphasizing the importance of early recognition and tailored management to improve long-term outcomes in children."

Journal • Review • Cardiovascular • Cataplexy • CNS Disorders • Developmental Disorders • Excessive Daytime Sleepiness • Hematological Disorders • Insomnia • Movement Disorders • Narcolepsy • Obstructive Sleep Apnea • Pediatrics • Psychiatry • Respiratory Diseases • Restless Legs Syndrome • Sleep Disorder

Narcolepsy with co-occurring epilepsy: diagnostic pitfalls and management strategy. (PubMed, Ther Adv Neurol Disord) - "Both conditions generally responded well to combined standard treatments, such as pitolisant, sodium oxybate, lamotrigine and valproate, though antiseizure medications occasionally worsened sleepiness. This study underscores the diagnostic pitfalls associated to overlapping symptoms of narcolepsy and epilepsy and emphasises the value of multidisciplinary diagnostic collaboration for the timely recognition and effective management of these coexisting neurological disorders."

Journal • CNS Disorders • Epilepsy • Excessive Daytime Sleepiness • Mental Retardation • Narcolepsy • Psychiatry • Sleep Disorder • HLA-DQB1

Sarcoidosis and Obstructive Sleep Apnoea: An Intriguing Relationship. (PubMed, Open Respir Med J) - "Despite increasing recognition, current evidence is limited by small sample sizes, heterogeneous diagnostic methods, and confounding effects of corticosteroid therapy. Future studies should clarify pathophysiological mechanisms, evaluate the impact of OSA treatment on sarcoidosis outcomes, and investigate wake-promoting agents such as solriamfetol and pitolisant as potential adjunctive therapies in patients with residual EDS."

Journal • Review • CNS Disorders • Excessive Daytime Sleepiness • Fatigue • Immunology • Inflammation • Myositis • Obesity • Obstructive Sleep Apnea • Pulmonary Disease • Respiratory Diseases • Sarcoidosis • Sleep Apnea • Sleep Disorder

Psychopharmacology of Eugeroics-The Whole Nine Yards! (PubMed, Psychopharmacol Bull) - "Eugeroics are a distinct, yet heterogeneous group of psychotropic agents that differ from classical stimulants, are less activating, of less abuse potential, sorely clinically underutilized, and have an attractive pharmacological portfolio speaking to the idea of pluripotent molecules of an expanded therapeutic potential. Herein, authors would touch briefly on the current available literature on eugeroics as germane to psychiatric practice whilst examining the extant evidence."

Journal • Review • Psychiatry

Histamine shapes the neurocomputational dynamics of human learning. (PubMed, Nat Commun) - "Using a first-in-class causal probe (H3R inverse agonist pitolisant), we show how elevating histamine shapes offline and online temporal-hippocampal dynamics - sustaining episodic learning-related activity and polarising retrieval computations. Beyond this, histamine adaptively shifts neurocomputational strategy under high working memory load, while stabilising value updates during aversive reinforcement learning. These findings uncover a mechanistically grounded influence of this underexplored system on human neurocomputation, supporting its therapeutic potential in psychiatry."

Journal • Psychiatry

Design, synthesis and pharmacological evaluation of novel 2-aryloxazole-based H3 receptor antagonists as potent, antiseizure agents. (PubMed, Mol Divers) - "Among the synthesized compounds, 4f exhibited the most potent H3R antagonistic activity (IC50 = 0.056 µM), superior to lead compound 5 g and the reference drug Pitolisant (PIT)...Preliminary safety profiling indicated minimal neurotoxicity at therapeutic doses and a lower hERG channel inhibition risk compared to PIT. These results identify 4f as a potent, selective, and brain-penetrable H3R antagonist with robust antiseizure activity and a favorable preclinical profile, supporting its further development as a novel antiseizure agent."

Journal • CNS Disorders • Epilepsy

A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension (clinicaltrials.gov) - P2 | N=65 | Completed | Sponsor: Harmony Biosciences Management, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2028 ➔ Jan 2026

Trial completion • Trial completion date • Prader–Willi syndrome • Sleep Disorder

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

Harmony Biosciences Reports Q1 Financial Results and Confirms 2026 Net Revenue Guidance of Over $1 Billion; Reinforces 2026 Strategic Priorities (PharmiWeb) - "Pitolisant GR (gastro-resistant)...NDA submission on track for Q2 2026; anticipated PDUFA date in Q1 2027...Phase 3 registrational clinical trials ongoing in narcolepsy (ONSTRIDE 1) and idiopathic hypersomnia (IH) (ONSTRIDE 2)...anticipated PDUFA date in 2028...EPX-100 (clemizole hydrochloride)....potential PDUFA date in 2028."

FDA filing • PDUFA • Epilepsy • Narcolepsy

Pitolisant disrupts memory consolidation and hippocampal synaptic plasticity: Impaired excitability and long-term potentiation in the CA1 area. (PubMed, Iran J Basic Med Sci) - "Additionally, LTP was reduced in pitolisant-treated groups, indicating disrupted long-term plasticity. These findings highlight a potential inhibitory effect of pitolisant on passive-avoidance memory consolidation in healthy rats and on hippocampal synaptic function, raising concerns about its use in neurological disorders."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • Narcolepsy • Sleep Disorder

A Study of Pitolisant in Patients With Prader-Willi Syndrome (clinicaltrials.gov) - P3 | N=134 | Recruiting | Sponsor: Harmony Biosciences Management, Inc. | N=67 ➔ 134

Enrollment change • Prader–Willi syndrome

Effects of Histamine H3 Receptor Antagonist/Inverse Agonist Pitolisant on Temporal Prediction, Spatial Switching, and Spontaneous Locomotion in Mice. (PubMed, Neuropsychopharmacol Rep) - "Together, these findings indicate that histamine H3 receptor signaling exerts selective behavioral influences, with minimal impact on temporal prediction and spatial switching behavior under the present task conditions but clear effects on physiological and motor domains. This work refines the understanding of histaminergic modulation in complex behavior and highlights important considerations for interpreting the cognitive and noncognitive consequences of H3 receptor-targeting therapeutics."

Journal • Preclinical

A Phase 3 Efficacy and Safety Study of HBS-301 in Participants With Idiopathic Hypersomnia (IH) (clinicaltrials.gov) - P3 | N=248 | Recruiting | Sponsor: Harmony Biosciences Management, Inc.

New P3 trial • Sleep Disorder

The headache- and migraine-inducing effects of pitolisant in women with migraine without aura (clinicaltrialsregister.eu) - P1/2 | N=14 | Not yet recruiting | Sponsor: Syddansk Universitet (University of Southern Denmark)

New P1/2 trial • CNS Disorders • Migraine • Pain

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