Vanda's HETLIOZ Hits Primary Endpoint in Phase III Delayed Sleep-Wake Phase Disorder Trial
核心洞察
Vanda Pharmaceuticals reported positive topline Phase III results for HETLIOZ (tasimelteon) 20 mg in adults with Delayed Sleep-Wake Phase Disorder (搜索), meeting the study's primary endpoint.
Tasimelteon shifted sleep onset 42.5 minutes earlier versus 5.4 minutes on placebo, a 37.1-minute difference from placebo with p=0.022.
In an exploratory responder analysis, 60% of tasimelteon-treated participants advanced sleep timing by at least 30 minutes versus 15% on placebo (p=0.008).
Vanda Pharmaceuticals has reported positive topline results from its pivotal Phase III study of HETLIOZ (tasimelteon) 20 mg in adults with Delayed Sleep-Wake Phase Disorder (搜索) (DSWPD), with the trial meeting its primary endpoint. The company said it intends to discuss the data with the U.S. Food and Drug Administration and submit a supplemental New Drug Application (sNDA) seeking approval of HETLIOZ for DSWPD. If approved, HETLIOZ would be the first FDA-approved medicine indicated for the condition.
Trial Design and Population
The study, VP-VEC-162-3502 (NCT04652882), was a multicenter, double-blind, randomized, placebo-controlled Phase III trial. Adults 18 to 75 years of age with a confirmed clinical diagnosis of DSWPD received once-daily oral tasimelteon 20 mg or matching placebo for 28 days. The study evaluated over 260 individuals and enrolled a total of 43 patients with DSWPD across 26 clinical sites in the US and Europe over a period of more than five years.
The primary endpoint was the start time of the sleep episode, measured by sleep diary.
Primary Endpoint Results
HETLIOZ 20 mg (n=20) shifted the time of sleep onset 42.5 minutes earlier, compared with a 5.4-minute shift on placebo (n=20), a 37.1-minute difference from placebo (p=0.022).
In an exploratory responder analysis, 60% of tasimelteon-treated participants (12/20) advanced their sleep timing onset by at least 30 minutes, compared with 15% on placebo (3/20) (p=0.008).
Safety over the 28-day controlled period was consistent with the established HETLIOZ label, and no new safety signals were identified.
An Existing Circadian Regulator, a Third Indication
HETLIOZ is a dual melatonin MT1 and MT2 receptor agonist and is already an approved circadian regulator. The FDA first approved it in 2014 to treat Non-24-Hour Sleep-Wake Disorder (搜索) in adults, and in 2020 to treat nighttime sleep disturbances in people with Smith-Magenis Syndrome (搜索), with capsules indicated in patients 16 years and older and HETLIOZ LQ oral suspension in patients 3 to 15 years of age. It is not currently approved for DSWPD. The DSWPD program would extend the same medicine, at the same 20 mg dose, to a third circadian sleep-wake disorder.
Vanda said the planned sNDA is expected to include this Phase III study together with the company's prior studies in related disorders and more than a decade of use in two approved circadian indications.
Disease Burden and Unmet Need
DSWPD is described by the company as a body-clock disorder rather than simply being a "night owl." In a typical night owl, late bedtimes are a preference; in DSWPD, the internal clock is stably set too late. People with the disorder often cannot fall asleep until the early morning hours even when they get into bed at a conventional time, then cannot wake for work, school, or family life the next morning even if they allow a full night in bed.
Estimated prevalence in adults is 0.2% to 1.5%, or roughly 0.5 to 4.1 million adults in the United States. The condition is often comorbid with other common psychiatric disorders.
"People with DSWPD often remain undiagnosed and undertreated especially because of the absence of a proven approved treatment," said Mihael H. Polymeropoulos, M.D., President, CEO and Chairman of the Board of Vanda. "This study extends our knowledge of the clinical properties of HETLIOZ as a versatile circadian regulator. We look forward to discussing these data with the FDA and pursuing a new indication for HETLIOZ as the first ever approved treatment for DSWPD."