Key points are not available for this paper at this time.
Abstract Introduction Narcolepsy is a lifelong sleep disorder characterized by a classic tetrad of excessive daytime sleepiness (EDS) with irresistible sleep attacks, cataplexy, hypnagogic hallucination, and sleep paralysis. The currently available treatments suffer from major limitations like side effects, modest efficacy or they must be prescribed in combination. 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 suggest a favorable risk/benefit profile for samelisant. Methods Samelisant had been evaluated as monotherapy in a Phase-2 proof of concept study in the USA and Canada for the treatment of EDS in patients with narcolepsy (ClinicalTrials.gov Identifier: NCT04072380). Patients 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 were recruited in the study. A total of 190 patients were randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio and received either placebo or samelisant, once daily for 2 weeks. The primary efficacy endpoint was change in ESS score from baseline to Day 14. Secondary endpoints were changes from baseline to week 2 in Clinical Global Impression - Severity (CGI-S) and MWT scores. The medical monitor and the data safety monitoring committee monitored safety throughout the study. Results The baseline characteristics and demographics were consistent with the general narcolepsy population and equally distributed between treatment groups. The study met the pre-specified primary efficacy endpoint. In comparison against placebo, samelisant as monotherapy demonstrated statistically significant (p 0.024) and clinically meaningful reduction (-2.1 point) in EDS measured by ESS. Samelisant was generally safe and well tolerated. Conclusion Samelisant holds promise as a monotherapy treatment of EDS in narcolepsy. Support (if any)
Nirogi et al. (Sat,) studied this question.