0609 Samelisant, Histamine 3 Receptor Agonist for the Potential Treatment of Excessive Daytime Sleepiness in Patients with Narcolepsy

Abstract

Abstract Introduction Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor inverse agonist. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of narcolepsy. Safety and tolerability studies in animals and healthy human volunteers suggested a favorable risk/benefit profile for samelisant. Methods Samelisant is currently being evaluated in a double blind, Phase-2 proof of concept study in USA and Canada for narcolepsy with or without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). The study is recruiting subjects diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of < 12 min. A total of 171 subjects are expected to be randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio. Each subject will receive either placebo or study drug once daily for 2 weeks. The primary efficacy endpoint is change in MWT score from baseline to week 2. Key secondary endpoint is change in ESS from baseline to week 2. Safety will be monitored throughout the study by medical monitor and by data safety monitoring committee. As the study is still recruiting, demographics and baseline characteristic data for the currently enrolled subjects is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion. Results At the data cutoff date of Nov 30, 2022, a total of 155 subjects were randomized in the study. The median age of subjects was 30 years (range: 18-57 years) with mean BMI of 28.5 kg/m2 (range: 18.3- 43.9 kg/m2). Overall, 57% subjects were of narcolepsy type-1, 71% were female and 71% were Caucasian. Mean (SD) baseline values of MWT and ESS scores were 6.1 (4.4) and 17.2 (2.8), respectively. Conclusion Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling subjects with narcolepsy and the data readout is expected in Q2 2023. Support (if any)