0641 Tasimelteon Demonstrates Efficacy in Improving Sleep Disturbances of Individuals with Smith-Magenis Syndrome (SMS)

Abstract

Introduction: Smith-Magenis Syndrome (SMS) is a rare (1 /15,000 - 25,000 births) developmental disorder that results from an interstitial deletion of human chromosome 17p11.2, and in rare cases from an RAI1 gene mutation. Patients with SMS present with a number of physical, mental, and behavioral problems. The most common symptom of SMS is a severe sleep disorder associated with significant disruption in the lives of patients and their families. Method(s): This study was a double-blind, randomized, two-period, 4-week crossover study that evaluated the effects of tasimelteon versus placebo on sleep disturbances of individuals with SMS. 25 patients with SMS were enrolled and evaluated for daily diary sleep quality (DDSQ) and for daily diary total nighttime sleep duration (DDTST) via a parental post sleep questionnaire (PSQ). Total nighttime sleep duration was also measured via daily actigraphy. Result(s): Tasimelteon met the primary endpoint of improvement in the 50% worst sleep quality (tasimelteon=0.67; placebo=0.27, p=0.0139) and showed improvement on the primary endpoint of 50% worst total nighttime sleep duration (tasimelteon=36.1 min; placebo=17.6 min, p=0.0556). Tasimelteon demonstrated significant improvement in overall sleep quality (tasimelteon=0.55; placebo= 0.22, p=0.0155) and overall total nighttime sleep duration (tasimelteon=40.9 min; placebo=19.8 min, p=0.0134). Tasimelteon improved the overall total nighttime sleep duration by an average of approximately 41 minutes per night, a highly clinically meaningful effect. Tasimelteon also showed significant improvement in objective measures of total nighttime sleep duration via actigraphy, for 50% worst total sleep time (TST) (tasimelteon=22.3 min; placebo= 2.4 min, p=0.0309) and overall TST (tasimelteon=20.1 min; placebo=1.9 min, p=0.0218). Conclusion(s): Tasimelteon demonstrated clinically meaningful and statistically significant improvements in sleep quality and total sleep time in SMS patients. These results suggest that tasimelteon can be a novel therapy for the treatment circadian dysfunction and sleep disturbance in patients with SMS.