As Vanda Pharmaceuticals awaits a long-sought hearing with the FDA around a potential Hetlioz label expansion into jet lag disorder, the melatonin receptor agonist has demonstrated its merit in another sleep indication with a current dearth of treatment options.
In a late-stage study of Hetlioz in adults with a confirmed clinical diagnosis of delayed sleep-wake phase disorder (DSWPD), Vanda’s circadian regulator drug shifted the time of sleep onset 42.5 minutes earlier for patients on treatment, versus a 5.4-minute shift on placebo.
That allowed the trial to meet its primary endpoint, which focused on the start of a participant’s sleep episode, as measured by a sleep diary, Vanda said in a release.
In an exploratory analysis from the study—which looked at more than 260 people and enrolled 43 who specifically had DSWPD at sites across the U.S. and Europe—60% of patients on Hetlioz (12 out of 20) advanced their sleep timing onset by at least 30 minutes, compared with 15% (3 out of 20) in the control cohort.
Safety in the trial was on par with Hetlioz’s known profile, said Vanda, which pointed out that there are currently no FDA-approved therapies specifically indicated for DSWPD.
A body-clock disorder, DSWPD is not simply being a ‘night owl,’ as Vanda puts it, but a condition in which the body’s internal clock is “stably set too late.”
People with the condition frequently have trouble falling asleep until the early hours of the morning, even after getting into bed at a normal time, and then struggle to wake up the next morning. Vanda noted that the condition is often accompanied by other psychiatric disorders and that it appears in some 0.5 to 4.1 million adults in the U.S.
With a trial win in hand, Vanda says it now plans to discuss the results with the FDA and file for a potential approval of Hetlioz in DSWPD.
If approved, Hetlioz would be picking up its third FDA nod for a circadian sleep-wake disorder, following an initial 2014 approval in non-24-hour sleep-wake disorder and a subsequent green light to treat nighttime sleep disturbances in those with Smith-Magenis Syndrome in 2020.
Vanda clarified that it would be seeking approval for “that same medicine, at the same 20 mg dose.”
For its approval filing, Vanda said it will leverage the trial results published Tuesday, alongside prior studies in the drug’s approved circadian indications.
The expansion prospects for Hetlioz in DSWPD come as Vanda has been fighting to land another label expansion for the medicine in jet lag disorder.
After the drug was rejected in that potential indication for a third time in January, Vanda got its wish for a hearing with the FDA on the matter in March, with that meeting now slated for mid-December.
Vanda had sought such a hearing since the FDA first snubbed its jet lag indication bid in 2019 and took the matter to court in 2022 before coming to a tentative agreement with the regulator in Oct. 2025.
In its latest rebuke, the FDA told Vanda it had concerns that the company’s clinical trial protocols weren’t sufficiently analogous to actual jet travel—a position the company disagreed with.