To evaluate the potential utility of Samelisant for the management of cataplexy

Narcolepsy is a chronic neurological disorder categorized into narcolepsy type-1 (NT1) and narcolepsy type-2 (NT2) disorder. The hallmark feature of the NT1 patients is the cataplexy symptoms. Although several therapies have been approved for the management of cataplexy, there remains a void, specifically in terms of safety, such as abuse liability, drug interactions, and cardiovascular risks.

Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor inverse agonist was characterized for its effects on cataplexy-like symptoms in orexin knockout mice and orexin-B SAP lesioned rats. Cataplectic like episodes were quantified using electroencephalography (EEG). Cortical norepinephrine levels were monitored through rat brain microdialysis technique.

Samelisant produced significant reduction in cataplectic like episodes in animal models. Samelisant treatment effects could be associated with the significant increase in cortical norepinephrine levels in rats.

Samelisant will be evaluated in a Phase-2 proof-of-concept study in the USA and Canada for its effect on cataplexy in patients with narcolepsy. The study will recruit about 129 NT1 patients. The study is a placebo-controlled, double blind randomized, parallel-group study. After a prescreening period of 4-weeks, eligible patients will enter a 2-week baseline period to assess number of weekly cataplexy attacks. Patients who are with continued presence of cataplexy as defined by at least 14 cataplexy attacks in a typical 2-week baseline period will be eligible. The primary objective of the study will be to evaluate changes in weekly cataplexy rates in NT1 patients.

The Phase-2 study results will inform the therapeutic utility and safety of Samelisant for the treatment of cataplexy in NT1 patients.