HETLIOZ® (tasimelteon) Demonstrates Efficacy to Treat Jet Lag Disorder in an 8 Hour Phase Advance Clinical Study

– HETLIOZ® demonstrates improvement in Total Sleep Time by 85 minutes versus Placebo (p<0.0001)

– HETLIOZ® demonstrates improvement in Next Day Alertness versus Placebo (p<0.01)

WASHINGTON, DC, USA I March 5, 2018 I Vanda Pharmaceuticals Inc. (Vanda) (NASDAQ: VNDA) today announced that HETLIOZ^®, a circadian regulator, demonstrated significant and clinically meaningful benefits in nighttime and daytime symptoms of jet lag disorder.  HETLIOZ^® is currently approved in the US and Europe for the treatment of Non-24-hour sleep-wake disorder, a rare and chronic circadian rhythm sleep disorder.

Jet lag disorder is a common circadian disorder frequently observed in millions of travelers who cross multiple time zones. Jet lag disorder is characterized by nighttime sleep disruption, a decrease in daytime alertness and impairment to social and occupational functioning.

The clinical efficacy results reported today are from the JET8 Phase-III clinical study (3107) (the JET8 study). In the JET8 study, 318 healthy volunteers were admitted to a sleep unit and were subjected to a circadian challenge of an 8 hours advance to their usual bedtime. The JET8 study design induced the circadian challenge experienced by travelers who cross 8 times zones, which leads to jet lag disorder.  This clinical design allowed for the study of HETLIOZ^® without the confounding effects of sleep deprivation and variable light conditions.

Results from the JET8 study showed significant and clinically meaningful effects of HETLIOZ^® 20 mg on the primary endpoint of the study as well as multiple secondary endpoints. The pre-specified primary endpoint was the amount of sleep time in the first two thirds of the night. Secondary endpoints included measures of sleep parameters (TST, LPS, WASO) and next day alertness (KSS and VAS). (Table 1).

Table 1: Summary of Primary and Key Secondary Endpoint Results

*Primary endpoint.

The results of the JET8 study shown above demonstrate the effectiveness of HETLIOZ^® in treating jet lag disorder. The magnitude of the total sleep time benefit of 85 minutes improvement over placebo is significant and clinically meaningful. The demonstration of benefits in measurements of next day alertness on both KSS and VAS is meaningful and it underscores the ability of HETLIOZ^® to address both nighttime and daytime symptoms of jet lag disorder.

Vanda previously reported on the JET5 study (3101) that examined the effects of HETLIOZ^® in a circadian challenge of 5 hours advance of the subjects’ usual bedtime. The results of that study were published in The Lancet in 2009.¹  The observation that HETLIOZ^® is effective in treating the symptoms caused by an abrupt advance of the circadian cycle of a magnitude of 5 or 8 hours suggests that HETLIOZ^® will be an effective therapeutic tool in the treatment of individuals that experience symptoms of jet lag. HETLIOZ^® will be potentially useful under circumstances of rapid eastward transmeridian travel experienced by frequent travelers, the rapid deployment of military troops and any circumstances that will necessitate the abrupt phase advance of the sleep wake cycle.

Jet lag disorder affects millions of individuals annually who cross multiple time zones during their travel. Jet lag disorder symptoms are more severe during eastward travel.  It is reported that more than 30 million US residents make trips abroad each year to overseas destinations.  Of these, 60% (approximately 20 million) travel to destinations in Europe, Middle East and Asia.  It is also reported that 8% (approximately 1.6 million) travel in Business or First class.²

“We are extremely pleased with the outcome of this study which establishes the utility of HETLIOZ^® in the treatment of jet lag disorder as HETLIOZ^® was shown to overcome a significant circadian challenge of an 8 hour phase advance. This challenge is equivalent to eastward travel across 8 time zones as experienced for example on travel from Los Angeles to London, Washington DC to Moscow, Paris to Tokyo, or London to Singapore. HETLIOZ^® improved both nighttime sleep and next day alertness potentially offering significant benefits to millions of travelers,” said Mihael H. Polymeropoulos, MD, Vanda’s President and CEO.

Vanda intends to seek marketing approval for the use of HETLIOZ^® in the treatment of jet lag disorder.  Vanda believes that if HETLIOZ^® is approved by regulatory authorities for the treatment of jet lag disorder it will potentially offer a therapeutic solution to many travelers and will likely represent an important commercial opportunity for the company.  For review of the current prescribing information of HETLIOZ^® please visit www.hetlioz.com.

Conference Call

The Vanda management team will host a conference call and live webcast today, March 5, 2018, at 8:30 AM ET to discuss these updates.  Investors can call 1-888-771-4371 (domestic) or 1-847-585-4405 (international) and use passcode 46600533. A replay of the call will be available on Monday, March 5, 2018, beginning at 11:00 AM ET and will be accessible until Monday, March 12, 2018, at 11:59 PM ET. The replay call-in number is 1-888-843-7419 for domestic callers and 1-630-652-3042 for international callers. The passcode number is 46600533.

The conference call will be broadcast simultaneously on Vanda’s website. Investors should click on the Investor Relations tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda’s website for a period of 30 days.

HETLIOZ^® IS NOT CURRENTLY APPROVED BY ANY REGULATORY AUTHORITY FOR THE TREATMENT OF JET LAG DISORDER.

About HETLIOZ^®

HETLIOZ^® is a melatonin receptor agonist. HETLIOZ^® has been granted market authorization by the U.S. Food and Drug Administration and the European Medicines Agency.  For full U.S. prescribing information, please visit www.hetlioz.com.