Positive Topline Results from Pivotal Phase III Study of HETLIOZ in Delayed Sleep-Wake Phase Disorder – Vanda Pharmaceuticals

 Vanda Pharmaceuticals Inc. 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 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.

Clinical Study results

VP-VEC-162-3502 (NCT04652882) was a multicenter, double-blind, randomized, placebo-controlled Phase III study. 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).

Endpoint: Sleep onset timing change, mean (min)
Placebo (N=20): 5.4
Tasimelteon 20 mg (N=20): 42.5
P-value: 0.022

Endpoint: ≥30-minute sleep timing advance
Placebo (N=20): 15% (3/20)
Tasimelteon 20 mg (N=20): 60% (12/20)
P-value: 0.008

Primary endpoint: change of sleep onset timing ( as compared to placebo.

Exploratory responder analysis defined as people with at least 30 minutes of advance of the sleep onset timing. P-value is from Fisher’s exact test.

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. 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.” – Mihael H. Polymeropoulos, M.D., President, CEO and Chairman of the Board.

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.