Vanda announced Hetlioz (tasimelteon) improved sleep quality and increased sleep duration in patients with Smith-Magenis Syndrome (SMS) in a pivotal placebo controlled clinical study.
"We are extremely pleased with the results of this study of tasimelteon in patients with Smith-Magenis Syndrome. Tasimelteon was shown to meaningfully improve sleep in SMS patients, addressing an unmet medical need for the most severe symptom constellation of this rare disorder," said Mihael H. Polymeropoulos MD, Vanda's President and Chief Executive Officer.
VEC-162-2401 was a double masked 4 week cross-over pivotal clinical trial that studied the effects of tasimelteon versus placebo in 25 patients with SMS. Patients were 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. The study had two predefined primary endpoints: DDSQ and DDTST.
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Tasimelteon met the primary endpoint of improvement in the 50% worst sleep quality (DDSQ) (p=0.0139) and also showed improvement on the primary endpoint of 50% worst total nighttime sleep duration (DDTST) (p=0.0556) (Table 1).
Tasimelteon demonstrated significant improvement in overall sleep quality (DDSQ) (p=0.0155) and overall total nighttime sleep duration (DDTST) (p=0.0134). Tasimelteon improved the overall total nighttime sleep duration (DDTST) by an average of approximately 41 minutes per night, a highly clinically meaningful effect. Given that most of the baseline nights were of shortened sleep duration, tasimelteon also improved sleep duration for the best half of the baseline nights versus placebo (50% best DDTST, 46.6 min, p=0.0052). Tasimelteon also showed significant improvement in subjective measures of total nighttime sleep duration via actigraphy, for 50% worst TST (p=0.0309) and overall TST (p=0.0218) (Table 1).
In this study, aberrant behaviors improved from baseline on both tasimelteon and placebo but likely due to the relative short duration of the study the differences were not significant between the two groups. In a longer open label study of tasimelteon in SMS, patients were treated for a period of approximately 27 weeks following a 6 week baseline evaluation. In that study, significant improvements from baseline were observed in sleep quality (DDSQ, p=0.0105) as well as in aberrant behaviors (Aberrant Behavior Checklist, p=0.0006).
The improvements in sleep quality and sleep duration demonstrated in the 2401 study were consistent across patients with chromosomal deletions of various lengths as well as a single patient with a point mutation in the RAI1 gene on chromosome 17p. The detailed results are expected to be presented in upcoming meetings and peer reviewed publications.
"Individuals with Smith-Magenis syndrome have significantly impaired sleep with altered sleep-wake cycles. This chronic sleep deprivation impacts cognitive and behavioral function on a daily basis. The sleep disturbance that occurs in this disorder impacts the entire family. The improved sleep duration and sleep quality with tasimelteon as shown in this study can provide a significant improvement to quality of life for individuals and families affected by this complex genetic condition" said Dr. Sarah Elsea, Professor, Baylor College of Medicine and Chair, PRISMS Professional Advisory Board.
VEC-162-2401 is the largest placebo controlled study ever conducted demonstrating significant sleep improvements in patients with SMS. The U.S. Food and Drug Administration (FDA) has granted orphan drug designation for tasimelteon for the treatment of SMS. Vanda intends to meet with regulatory authorities and seek marketing authorization for the treatment of SMS patients with tasimelteon.
Hetlioz is currently approved for the treatment of Non-24 Hour Sleep Wake Disorder.