Vanda Reports Positive Phase 3 HETLIOZ Results in Delayed Sleep-Wake Phase Disorder

Key Points

• HETLIOZ (tasimelteon) met the primary endpoint in Vanda Pharmaceuticals’ Phase 3 trial for delayed sleep-wake phase disorder (DSWPD).
• After 28 days, patients taking HETLIOZ fell asleep 42.5 minutes earlier than at baseline, versus 5.4 minutes earlier with placebo—a 37.1-minute difference between groups.
• Vanda plans to seek FDA approval for DSWPD through a supplemental New Drug Application, but has not provided a filing date.
• No new safety signals were identified during the 28-day controlled period.
• HETLIOZ is already approved for two other circadian sleep-wake indications; it is not approved for DSWPD.

Vanda Pharmaceuticals (NASDAQ: VNDA) reported positive topline results from a late-stage study of HETLIOZ in adults with DSWPD, a condition in which a persistently delayed body clock makes it difficult to fall asleep and wake at conventional times. The company intends to pursue a third FDA-approved indication for the medicine.

Phase 3 Trial Shows Earlier Sleep Onset With HETLIOZ

The randomized, double-blind, placebo-controlled trial tested a daily 20 mg oral dose for 28 days. It enrolled 43 adults with DSWPD across 26 sites in the U.S. and Europe; the primary-endpoint results reported by Vanda cover 20 patients in each treatment group.

Sleep onset, measured by patient diary, moved 42.5 minutes earlier in the HETLIOZ group and 5.4 minutes earlier in the placebo group, a 37.1-minute treatment difference (p=0.022). In an exploratory analysis, 60% of HETLIOZ-treated patients advanced sleep onset by at least 30 minutes, compared with 15% of placebo patients. Vanda said the treatment’s safety profile was consistent with its existing label, with no new safety signals identified over 28 days.

FDA Filing Could Expand an Existing Sleep-Disorder Label

Vanda plans to file a supplemental New Drug Application for DSWPD using this study, prior research in related disorders and experience from HETLIOZ’s approved uses. The FDA approved HETLIOZ for Non-24-Hour Sleep-Wake Disorder in adults in 2014 and for nighttime sleep disturbances associated with Smith-Magenis Syndrome in 2020.

If the FDA approves the proposed expansion, Vanda says HETLIOZ could become the first FDA-approved medicine for DSWPD. The company estimates the condition affects roughly 0.5 million to 4.1 million U.S. adults. That prevalence estimate is not a forecast of how many patients would receive treatment.

Investor Takeaway: A Positive Result, With Regulatory Review Ahead

For VNDA investors, the trial provides evidence supporting a potential new use for an already marketed drug at the same 20 mg dose. The next milestones are Vanda’s filing, the FDA’s review and any decision on the DSWPD indication. The announcement does not include a filing timeline, an approval date or a revenue forecast.