Vanda Pharmaceuticals Inc. (Nasdaq: VNDA) announced positive topline results from its pivotal Phase III study of HETLIOZ^® (tasimelteon) 20 mg in adults with Delayed Sleep-Wake Phase Disorder (DSWPD). Vanda intends to discuss these data with the U.S. Food and Drug Administration (FDA) and to 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 this condition.

HETLIOZ^® is already an approved circadian regulator. The FDA first approved it in 2014 to treat Non-24-Hour Sleep-Wake Disorder in adults, and in 2020 to treat nighttime sleep disturbances in people with Smith-Magenis Syndrome. The DSWPD program would extend that same medicine, at the same 20 mg dose, to a third circadian sleep-wake disorder.

Delayed Sleep-Wake Phase Disorder (DSWPD)

DSWPD is a body-clock disorder, and not 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.¹ Estimated prevalence in adults is 0.2% to 1.5%, or roughly 0.5 to 4.1 million adults in the United States.^2,3 The condition is often comorbid with other common psychiatric disorders. ^4,5

Clinical Study results

VP-VEC-162-3502 (NCT04652882) was a multicenter, double-blind, randomized, placebo-controlled Phase III study.⁶ 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 for a period of over 5 years.

The study met its primary endpoint. 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). The primary endpoint was the start time of the sleep episode, measured by sleep diary.

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. No new safety signals were identified.

"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. "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."

Vanda plans to file an sNDA for HETLIOZ^® in DSWPD. The application is expected to include this Phase III study together with Vanda's prior studies in related disorders and more than a decade of use in two approved circadian indications.