Tasimelteon safely and effectively improves sleep in Smith–Magenis syndrome: a double-blind randomized trial followed by an open-label extension

Abstract

Purpose To assess the efficacy of tasimelteon to improve sleep in Smith–Magenis syndrome (SMS). Methods A 9-week, double-blind, randomized, two-period crossover study was conducted at four US clinical centers. Genetically confirmed patients with SMS, aged 3 to 39, with sleep complaints participated in the study. Patients were assigned to treatment with tasimelteon or placebo in a 4-week crossover study with a 1-week washout between treatments. Eligible patients participated in an open-label study and were followed for >3 months. Results Improvement of sleep quality (DDSQ50) and total sleep time (DDTST50) on the worst 50% of nights were primary endpoints. Secondary measures included actigraphy and behavioral parameters. Over three years, 52 patients were screened, and 25 patients completed the randomized portion of the study. DDSQ50 significantly improved over placebo (0.4, p = 0.0139), and DDTST50 also improved (18.5 minutes, p = 0.0556). Average sleep quality (0.3, p = 0.0155) and actigraphy-based total sleep time (21.1 minutes, p = 0.0134) improved significantly, consistent with the primary outcomes. Patients treated for ≥90 days in the open-label study showed persistent efficacy. Adverse events were similar between placebo and tasimelteon. Conclusion Tasimelteon safely and effectively improved sleep in SMS.

Once-daily tasimelteon (VEC-162) for jet lag following transmeridian travel: A multicenter, randomized, double-blind, placebo-controlled trial

“…The results of the JET study support the pivotal JET5 and JET8 Phase III studies, which confirmed significant effects in circadian advances of 5- and 8-h, respectively, and add to the body of evidence of the effectiveness of tasimelteon in treating Jet Lag Disorder ( 11 ).…”

“…Tasimelteon (HETLIOZ®) has received market authorization for the treatment of Non-24-h Sleep-Wake Disorder (Non-24) ( 10 ), and for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) ( 11 ) by the United States (US) Food and Drug Administration and also for the treatment of Non-24 in totally blind individuals by the European Medicines Agency. By acting upon the MT 1 and MT 2 receptors, tasimelteon may also be useful for treating JLD by exerting both a circadian regulatory effect and potentially a soporific effect by quieting the circadian drive for wakefulness at the desired sleep time.…”

Smith-Magenis Syndrome—Clinical Review, Biological Background and Related Disorders

“…Tasimelteon is an oral melatonin receptor agonist that was developed for the treatment of circadian sleep–wake rhythm disorders. In 2020, this drug was approved in the US for the treatment of nighttime sleep disturbances in SMS [ 132 ]. Ramelteon, another melatonin agonist approved for the treatment of insomnia, has not been studied specifically in patients with SMS but has been shown to shift the circadian phase in individuals with jet lag [ 133 ] and might be effective also in SMS.…”