Vanda to Pursue sNDA for Tasimelteon in Delayed Sleep-Wake Phase Disorder After Positive Phase 3 Readout

Vanda Pharmaceuticals has announced that its tasimelteon (Hetlioz) shifted sleep onset 42.5 minutes earlier in adults with delayed sleep-wake phase disorder (DSWPD), compared with 5.4 minutes with placebo, meeting the primary end point of a phase 3 trial (NCT04652882). The 37.1-minute placebo-adjusted difference was statistically significant (P = .022), and the company noted that it plans to submit a supplemental new drug application (sNDA) to the FDA for the indication.¹

If approved, tasimelteon would become the first FDA-approved treatment for DSWPD, a circadian rhythm disorder in which the internal body clock is misaligned with desired sleep and wake times. The company estimates that 0.5 to 4.1 million US adults have the condition, which it distinguishes from a simple preference for late sleep timing.¹ Tasimelteon, a dual melatonin receptor agonist, is already approved for 2 other indications: non-24-hour sleep-wake disorder in adults, approved in 2014, and nighttime sleep disturbances in Smith-Magenis syndrome, approved in 2020.

The phase 3 study was a multicenter, double-blind, randomized, placebo-controlled trial conducted at 26 sites in the US and Europe over more than 5 years.² It enrolled 40 adults aged 18 to 75 years with confirmed DSWPD, who received tasimelteon 20 mg (n = 20) or placebo (n = 20).¹ The primary end point was the change in sleep onset timing during a 28-day controlled treatment period. Patients receiving tasimelteon advanced sleep onset by 42.5 minutes, versus 5.4 minutes for those receiving placebo, yielding the 37.1-minute difference.

Responder analysis and safety of tasimelteon in DSWPD

In an exploratory responder analysis, 60% of patients who received tasimelteon advanced their sleep timing by at least 30 minutes, compared with 15% of those who received placebo (P = .008). Safety findings during the 28-day controlled period were consistent with the established safety profile of tasimelteon, and the company reported no new safety signals. Because the controlled period lasted 4 weeks and enrolled 40 patients, the trial provides limited information on longer-term use or on uncommon adverse effects in this population.

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"People with DSWPD often remain undiagnosed and undertreated especially because of the absence of a proven approved treatment," Mihael H. Polymeropoulos, MD, president and CEO of Vanda, said in a statement.¹ The sNDA would seek to add DSWPD to the tasimelteon label, which would make it the first approved therapy for a disorder that currently has no FDA-approved pharmacologic option.

Frequently Asked Questions

What is tasimelteon approved for?

Tasimelteon is FDA approved for non-24-hour sleep-wake disorder in adults (2014) and for nighttime sleep disturbances in Smith-Magenis syndrome (2020). Vanda plans to seek approval for delayed sleep-wake phase disorder.

How does tasimelteon work?

Tasimelteon is a dual melatonin receptor agonist that acts on the body's circadian system, and the company describes it as a circadian regulator.

What did the phase 3 DSWPD trial show?

Tasimelteon 20 mg advanced sleep onset by 42.5 minutes versus 5.4 minutes with placebo, a 37.1-minute difference (P = .022), in 40 adults with DSWPD.

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REFERENCES
1. Vanda Pharmaceuticals. Vanda Pharmaceuticals announces positive phase III results for HETLIOZ (tasimelteon) in delayed sleep-wake phase disorder. Published September 29, 2026. Accessed September 30, 2026. https://vandapharmaceuticalsinc.gcs-web.com/node/17161/pdf
2. Study of tasimelteon in delayed sleep-wake phase disorder (VP-VEC-162-3502). ClinicalTrials.gov identifier: NCT04652882. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT04652882