0595 Long-term efficacy on cataplexy attacks and excessive daytime sleepiness in open-label extension study (NLS-1022) of mazindol ER

Abstract

Abstract Introduction Mazindol ER (extended-release), the first partial orexin-2 receptor agonist and triple mono-aminergic reuptake inhibitor, has demonstrated efficacy and safety in significantly reducing excessive daytime sleepiness (EDS) and cataplexy attacks in narcolepsy type 1 (NT1) and type 2 (NT2) patients (POLARIS, Study NLS-1021). This efficacy was further studied in an open-labeled extension (OLE) study (ClinicalTrials.gov Identifier: NCT04923594). Methods A multicenter, 6-month, OLE study with 51 narcolepsy patients previously enrolled in a double-blind mazindol ER study. Patients were administered 3mg mazindol ER once daily in the morning. Narcolepsy symptoms and adverse events were recorded. Safety measures included monthly physical and laboratory examinations. The primary efficacy measure was the change from baseline in EDS using the Epworth Sleepiness Scale (ESS). Secondary measures included weekly cataplexy attacks, the overall disease severity as rated by the investigators (Clinician Global Impression of Severity) and patients (Patient Global Impression of Severity). Results Mazindol ER at 3 mg once-daily doses, produced overall improvements in EDS and narcolepsy within 1-2 weeks of starting dosing. Reported improvements included diminished daytime sleepiness (p < 0.001); significant decreases in cataplexy attacks (p < 0.001); and multiple improvements in symptoms severity and function. Adverse events were generally mild and patients showed no evidence of tolerance. Conclusion Mazindol ER is a convenient, safe, well-tolerated and effective treatment for narcolepsy. Its anticataleptic and wake-promoting effects indicate that it may be a new therapeutic option for patients with NT1 or NT2 similar or better than various combinations treatments currently available. Support (if any) NLS Pharmaceutics