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

A proof-of-concept study of pitolisant for excessive daytime sleepiness in patients with Prader-Willi syndrome. (PubMed, J Clin Sleep Med) - P2 | "Results of this proof-of-concept study support further evaluation of pitolisant in patients with PWS and EDS."

Clinical • Journal • Excessive Daytime Sleepiness • Mood Disorders • Pain • Prader–Willi syndrome • Psychiatry • 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 Histamine H3 Receptor Antagonist/Inverse Agonist Including Betahistine for Schizophrenia: A Systematic Review and Meta-Analysis. (PubMed, Neuropsychopharmacol Rep) - "Some H3R-ANTs/H3R-IAs might provide benefit for the treatment of cognitive symptoms and depressive symptoms in individuals afflicted with schizophrenia."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Insomnia • Psychiatry • Schizophrenia • Sleep Disorder

Efficacy and safety of pitolisant in children above 6 years with narcolepsy. (PubMed, Expert Opin Pharmacother) - "With a favorable safety profile and good tolerability, pitolisant efficiently outperforms traditional therapies, which often have distressing side effects. Its use is particularly critical in childhood, a developmental stage where factors like growth, school performance, and socialization must be carefully considered, making it a transformative option for pediatric care."

Journal • Review • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Pediatrics • Prader–Willi syndrome • Sleep Disorder

Pilot study of Pitolisant, a histamine-3 inverse agonist, as adjunct therapy for refractory restless legs syndrome. (PubMed, Sleep Med) - "Pitolisant was generally well tolerated and improved RLS scales. The data suggests more improvement in daytime consequences of RLS compared to lessening of the core RLS symptoms. Controlled trials are justified."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Fatigue • Insomnia • Movement Disorders • Narcolepsy • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Pitolisant in the Management of Obstructive Sleep Apnea with Persistent Daytime Sleepiness Despite CPAP/APAP Adherence: A Retrospective Observational Study (ERS 2025) - No abstract available

Adherence • Observational data • Retrospective data • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Harmony Biosciences Strengthens Patent Position With Favorable Settlement in ANDA Litigation (Yahoo Finance) - "Harmony Biosciences Holdings, Inc...announced a settlement agreement with Lupin Limited, resolving the patent infringement litigation related to Lupin’s Abbreviated New Drug Application (ANDA) for a generic version of WAKIX (pitolisant hydrochloride). As part of the agreement, litigation in the United States District Court for the District of Delaware will be dismissed, and Lupin will receive a license to launch its generic product no earlier than January 2030 (or July 2030 with pediatric exclusivity), or earlier under certain circumstances."

Patent • Excessive Daytime Sleepiness in Narcolepsy

Efficacy and Safety of Pitolisant in Residual Excessive Daytime Sleepiness for Patients With Obstructive Sleep Apnea Adhering to Continuous Positive Airway Pressure Therapy: An Individual Patient Meta-Analytical Approach (ATS 2025) - "Pitolisant 20 mg and 40 mg were significantly therapeutically superior to placebo in treating residual EDS in patients with OSA who received CPAP on the outcomes for ESS, OSLER, and QoL."

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

Characteristics of Patients Enrolled in a Pharmacist Managed Rare Disease Program: Highlighting National Diversity and Representation (ISPOR 2025) - " Among the 7,633 patients enrolled in the Ph-RDP, 55% were diagnosed with sleep disorders, primarily treated with pitolisant, while 34% had sickle cell disease, with voxelotor being the most common medication. The findings highlight the program’s broad reach, including substantial patient enrollment from rural and urban areas and high vulnerability areas as a proxy for providing accessible care to underserved populations. Patient participation and high engagement levels, evidenced by the number of assessments and duration of enrollment, emphasize the program’s potential impact in improving care and health outcomes."

Clinical • CNS Disorders • Genetic Disorders • Hematological Disorders • Rare Diseases • Sickle Cell Disease • Sleep Disorder

Development and validation of a method for quantitative determination of the genotoxic impurity diethyl sulfate in pitolisant hydrochloride via high-performance liquid chromatography. (PubMed, RSC Adv) - "The method demonstrated an LOD and LOQ of 4 ppm and 12 ppm, respectively. This developed HPLC methodology proved to be well-suited for quantifying trace levels of the potential genotoxic impurity diethyl sulfate (DES) in pitolisant hydrochloride, a by-product originating from the synthesis process."

Journal

Harmony Biosciences Reports Strong Q1 2025 Financial Results, Highlights Advancement of Its Pipeline and Upcoming Catalysts, and Reaffirms 2025 Revenue Guidance ​ (Businesswire) - "WAKIX (pitolisant) Net Revenue of $184.7 Million for First Quarter 2025; Representing 20% Growth Year-over-Year....On track to initiate Phase 3 registrational trials in both narcolepsy and IH in Q4 2025 with potential PDUFA dates in 2028....Pitolisant GR (gastro-resistant): Topline data readout anticipated in Q3 2025 with potential PDUFA date in 2026. Orexin-2 receptor agonist (BP1.15205): Comprehensive preclinical safety and efficacy data to be presented at SLEEP 2025 (June)....IMPD submission on track for mid-2025; first-in-human study expected to initiate 2H 2025 with clinical data anticipated in 2026."

Clinical data • FDA approval • New trial • Sales • Narcolepsy • Sleep Wake Cycle Disorder

Acute hypobaric hypoxia attenuates the anti-fatigue effects of pitolisant by downregulating the expression of organic cation transporter 1 and P-glycoprotein. (PubMed, Front Pharmacol) - "Pitolisant shows potential for supporting circadian rhythm regulation in shift workers and individuals suffering from jet lag. When used under HH conditions, adjusting the dose and frequency may be necessary due to altered pharmacokinetics."

Journal • Fatigue • SLC22A1

Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness and Other Non-Muscular Symptoms in Patients With Myotonic Dystrophy Type 1 (clinicaltrials.gov) - P2 | N=30 | Completed | Sponsor: Harmony Biosciences Management, Inc. | Active, not recruiting ➔ Completed

Trial completion • Excessive Daytime Sleepiness • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • Sleep Disorder

Comparative Efficacy and Safety of Multiple Wake-Promoting Agents for the Treatment of Residual Sleepiness in Obstructive Sleep Apnea Despite Continuous Positive Airway Pressure: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. (PubMed, CNS Drugs) - "Among all WPAs, solriamfetol demonstrated the highest efficacy on ESS and MWT, with the latter being significant. Modafinil demonstrated the best clinician impression, albeit not statistically significant. All four WPAs were associated with a low risk of serious or adverse events."

Journal • Retrospective data • Review • CNS Disorders • Depression • Mood Disorders • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

Pitolisant alleviates brain network dysfunction and cognitive deficits in a mouse model of Alzheimer's disease. (PubMed, Transl Psychiatry) - "Furthermore, pitolisant reduced amyloid-β deposition and dystrophic neurites surrounding plaques, and enhanced neuronal lysosomal activity, inhibiting which blocked cognitive and slow-wave restoration. Our findings identify pitolisant as a potential therapeutic agent for AD treatments."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Narcolepsy • Sleep Disorder

Expert consensus on the diagnosis and treatment of excessive daytime sleepiness in obstructive sleep apnea (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "Surgical interventions can also be used as an adjunctive therapy to CPAP (2, B).Recommendation 6: OSA patients with EDS should make lifestyle changes, including correcting poor lifestyle habits and improving sleep hygiene, to improve nocturnal sleep quality and daytime alertness (3, B).Recommendation 7: Pharmacological wake-promoting agents may be considered, after careful clinical evaluation, in OSA patients who meet the following criteria: ① Residual EDS persists despite adequate and adherent conventional OSA therapy (including CPAP, oral appliances, and surgery) with exclusion of other EDS etiologies; ② Patients with EDS who refuse, are intolerant of, or are not compliant with conventional therapy; ③ Patients with EDS that severely impairs quality of life, interferes with work/study performance, or increases the risk of accidents (including those with actual or near-miss accidents) (expert consensus, ungraded).Recommendation 8: For patients with residual EDS despite..."

Journal • Cardiovascular • CNS Disorders • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

Personalized endpoints in Prader-Willi syndrome: a case study with goal attainment scaling. (PubMed, J Clin Sleep Med) - "This case report examines the implementation of Goal Attainment Scaling (GAS) for a 9-year-old girl with Prader-Willi Syndrome (PWS) and narcolepsy-like features who began treatment with Pitolisant, a medication designed to alleviate excessive daytime sleepiness...This method provided an unbiased assessment of treatment effectiveness, underscoring the importance of integrating patient-centered measures in the management of rare diseases like PWS. The findings suggest that GAS can yield valuable insights into patient priorities and treatment outcomes, highlighting the need for further research into its application in clinical settings for PWS and similar conditions."

Journal • Excessive Daytime Sleepiness • Narcolepsy • Prader–Willi syndrome • Rare Diseases • Sleep Disorder

Management options for excessive daytime sleepiness in patients with obstructive sleep apnea. (PubMed, Expert Rev Respir Med) - "Solriamfetol and pitolisant are wake-promoting agents (WPA) recently approved for use in sleepy OSA patients accepting or refusing OSA treatment...However, it is still uncertain which subgroups of patients should be treated for the symptom of EDS while maintaining a low-risk profile in terms of consequences of OSA on health. Until such data are available, use of WPA in OSA patients should be managed by Sleep Specialists."

Journal • Review • Cardiovascular • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Narcolepsy & Idiopathic Hypersomnia Patient Journey, Clinical Features and Treatments in a Real-World US Population (AAN 2025) - "Common treatments included SSRI/SNRI (57%), stimulants (41%), and wake-promoting agents (39%); 15% of NT1 patients received oxybate and 2.6% pitolisant...In a large real-world US population, sleep diagnostic evaluations were underutilized and many patients were untreated. A small proportion received narcolepsy-specific medications. These results indicate an unmet need for effective diagnostic and treatment strategies for patients with narcolepsy/IH."

Clinical • Real-world • Real-world evidence • Cardiovascular • CNS Disorders • Depression • Genetic Disorders • Mood Disorders • Narcolepsy • Obesity • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Substance Abuse

Franchise Highlights (Businesswire) - "Pitolisant HD (high-dose)...Phase 3 registrational trial in narcolepsy to include endpoint on narcolepsy-related fatigue in pursuit of differentiated label: Trial to initiate in Q4 2025; topline data readout anticipated in 2027 with potential PDUFA date in 2028; Phase 3 registrational trial in IH to include endpoint on sleep inertia in pursuit of differentiated label: Trial to initiate in Q4 2025; topline data readout anticipated in 2027 with potential PDUFA date in 2028; Provisional IP filed out to 2044 for narcolepsy and IH....Pitolisant GR (gastro-resistant): Pivotal bioequivalence study on track to initiate Q1 2025: Topline data readout anticipated in Q3 2025 with potential PDUFA in 2026; Provisional IP filed out to 2044."

Clinical data • FDA approval • New P3 trial • Patent expiry • Narcolepsy • Sleep Wake Cycle Disorder

WAKIX in Narcolepsy (Businesswire) - "Net Sales were $201.3M for Q4 2024 and $714.7M for FY 2024; 2025 Net Revenue projected between $820 to $860 million; Settlement reached in first Abbreviated New Drug Application (ANDA) litigation, giving Novugen Pharma a license to sell its generic product beginning in January 2030 or earlier under certain circumstances; This settlement reinforces the strength and durability of Harmony’s intellectual property portfolio and its vigorous defense of its patent estate; On track to obtain pediatric exclusivity which, if granted, would add an additional 6 months of regulatory exclusivity."

Generic launch • Patent • Sales • Narcolepsy

Interim analysis of a post-authorization safety study of pitolisant in treating narcolepsy: A real-world European study. (PubMed, Sleep Med) - "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."

Journal • Real-world evidence • Cardiovascular • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Genetic Disorders • Narcolepsy • Obesity • Psychiatry • Sleep Disorder

Harmony Biosciences Provides Update on the Status of the Supplemental New Drug Application for Pitolisant in Idiopathic Hypersomnia (Businesswire) - "Harmony Biosciences Holdings, Inc...today announced that it received a Refusal to File (RTF) letter from the U.S. Food and Drug Administration (FDA) for pitolisant for the treatment of excessive daytime sleepiness (EDS) in adult patients with idiopathic hypersomnia (IH)...'We are on track to initiate a Phase 3 registrational trial of Pitolisant HD in IH in Q4 2025, with a target PDUFA date in 2028.'"

FDA event • New P3 trial • PDUFA • Excessive Daytime Sleepiness • Sleep Disorder

Efficacy and safety of pitolisant in residual excessive daytime sleepiness for patients with obstructive sleep apnea adhering to continuous positive airway pressure therapy in the HAROSA studies: An individual patient meta-analytical approach. (PubMed, Sleep Med) - "Pitolisant 20 mg and 40 mg were significantly therapeutically superior to placebo in treating residual EDS in patients with OSA who received CPAP on the outcomes for ESS, OSLER, and QoL."

Journal • Excessive Daytime Sleepiness • Fatigue • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Harmony Biosciences Reports Strong 2024 Revenues, Provides 2025 Revenue Guidance and Highlights Key Pipeline Catalysts (Businesswire) - "Q1 – FDA decision on file acceptance of pitolisant sNDA for Idiopathic Hypersomnia (IH); IH sNDA for pitolisant submitted in Q4 2024; Potential FDA approval in 2025..."

FDA approval • FDA filing • Sleep Disorder