Vanda’s HETLIOZ (tasimelteon) shifted sleep onset 37.1 minutes earlier than placebo in a Phase III study of delayed sleep-wake phase disorder
Written By: Mayuri Vaja, PharmD
Reviewed By: Pharmacally Editorial Team
Vanda Pharmaceuticals reported that HETLIOZ (tasimelteon) 20 mg shifted sleep onset 37.1 minutes earlier than placebo in a pivotal Phase III study of adults with Delayed Sleep-Wake Phase Disorder (DSWPD), supporting plans for a U.S. supplemental New Drug Application.
Phase III Study Met Its Primary Endpoint
The randomized, double-blind, placebo-controlled study, VP-VEC-162-3502 (NCT04652882), evaluated once-daily oral tasimelteon 20 mg for 28 days in adults aged 18 to 75 years with confirmed DSWPD. The study enrolled 43 patients across 26 sites in the United States and Europe, with 40 participants included in the reported treatment comparison.
Tasimelteon shifted sleep onset by a mean of 42.5 minutes, compared with 5.4 minutes with placebo. The resulting 37.1-minute difference met the primary endpoint with a p-value of 0.022. Sleep onset timing was assessed using sleep diaries.
An exploratory responder analysis found that 60% of participants receiving tasimelteon achieved at least a 30-minute advance in sleep onset, compared with 15% in the placebo group (p=0.008).
Targeting a Delayed Circadian Clock
DSWPD is a circadian rhythm sleep-wake disorder in which the internal body clock is persistently shifted later than conventional sleep schedules. Patients may struggle to fall asleep at a socially typical bedtime and consequently have difficulty waking at required times despite allowing sufficient time for sleep. The source estimates that DSWPD affects approximately 0.2% to 1.5% of adults, corresponding to roughly 0.5 million to 4.1 million adults in the United States.
Tasimelteon is a dual melatonin MT1 and MT2 receptor agonist that regulates circadian signaling. The FDA previously approved HETLIOZ in 2014 for Non-24-Hour Sleep-Wake Disorder in adults and in 2020 for nighttime sleep disturbances associated with Smith-Magenis Syndrome. It is not currently approved for DSWPD.
Safety Consistent with Established Profile
Safety during the 28-day controlled treatment period was consistent with the established HETLIOZ prescribing information, and Vanda reported no new safety signals.
The reported efficacy therefore extends clinical evidence for tasimelteon into another circadian sleep-wake disorder while maintaining the same 20 mg dose used in its existing approved indications.
Vanda Plans FDA Submission
Vanda plans to discuss the Phase III findings with the FDA and submit an sNDA seeking approval of HETLIOZ for DSWPD. The proposed application is expected to include the new Phase III study, earlier studies in related disorders, and more than a decade of clinical use in the drug’s two existing circadian indications.
If approved, HETLIOZ would become the first FDA-approved medicine specifically indicated for DSWPD, according to Vanda. The regulatory outcome and timing remain uncertain because the company has not yet received FDA approval for the proposed indication.
Reference
Vanda Pharmaceuticals Announces Positive Phase III Results for HETLIOZ®(tasimelteon) in Delayed Sleep-Wake Phase Disorder, VANDA Pharmaceuticals, 29 September 2026
Evaluating the Effects of Tasimelteon vs. Placebo in Delayed Sleep-Wake Phase Disorder (DSWPD), ClinicalTrials.gov ID NCT04652882
About the Writer
Mayuri Vaja (Linkedin) is a Pharm.D professional with a strong interest in clinical research, pharmacovigilance, and medical writing, supported by certifications in pharmacovigilance and academic projects exploring AI in healthcare and drug safety.
With a growing focus on evidence-based healthcare and scientific communication, she is developing expertise in clinical research and translating healthcare evidence into clear, meaningful content.
As a Pharmacally healthcare writer, Mayuri is committed to creating accurate, research-driven, and clinically relevant healthcare content while continuously strengthening her professional skills.