Phase III Study Meets Primary Endpoint in Adults With DSWPD
Vanda Pharmaceuticals Inc. has reported positive topline results from a pivotal Phase III study evaluating HETLIOZ (tasimelteon) 20 mg in adults with Delayed Sleep-Wake Phase Disorder (DSWPD).
The company plans to discuss the results with the U.S. Food and Drug Administration (FDA) and submit a supplemental New Drug Application (sNDA) seeking approval of HETLIOZ for DSWPD.
HETLIOZ is not currently approved for DSWPD. If the FDA approves the proposed indication, Vanda said it would become the first FDA-approved medicine specifically indicated for the condition.
What Is Delayed Sleep-Wake Phase Disorder?
Delayed Sleep-Wake Phase Disorder is a disorder of the body's internal biological clock.
It is different from simply preferring to stay up late.
A person who likes going to bed late may still be able to sleep at a normal time when needed. In DSWPD, the body's internal clock is consistently shifted to a later schedule.
People with DSWPD may not feel sleepy until the early morning hours. As a result, they can have difficulty waking up at the time required for work, school or family responsibilities.
Even when they have enough time available for a full night's sleep, their sleep schedule can remain significantly delayed.
DSWPD Affects Millions of Adults
Vanda estimates that DSWPD affects between 0.2% and 1.5% of adults.
That represents roughly 0.5 million to 4.1 million adults in the United States.
The disorder can also occur alongside other psychiatric conditions.
Because the symptoms can look like poor sleep habits or a preference for staying up late, some people with DSWPD may remain undiagnosed or undertreated.
Phase III Study Evaluated HETLIOZ 20 mg
The Phase III study was identified as VP-VEC-162-3502 and registered as NCT04652882.
It was a multicenter, double-blind, randomized and placebo-controlled clinical trial.
Adults between 18 and 75 years of age with a confirmed diagnosis of DSWPD were enrolled.
Participants received either HETLIOZ 20 mg or a matching placebo once daily for 28 days.
The broader study evaluated more than 260 individuals, while 43 participants with confirmed DSWPD were ultimately enrolled across 26 clinical sites in the United States and Europe.
The DSWPD portion of the program took place over more than five years.
HETLIOZ Shifted Sleep Timing Earlier
The study met its primary endpoint.
Among the participants included in the primary analysis, those receiving HETLIOZ 20 mg experienced an average 42.5-minute advance in the time they started their sleep episode.
The placebo group experienced a 5.4-minute shift.
This represented a 37.1-minute difference between HETLIOZ and placebo.
The result was statistically significant, with a p-value of 0.022.
The primary endpoint was based on the change in sleep onset timing recorded through sleep diaries.
In simple terms, participants taking HETLIOZ were able to move the beginning of their sleep period earlier than participants receiving placebo.
More Participants Achieved a 30-Minute Improvement
Vanda also reported an exploratory responder analysis.
In this analysis, a responder was defined as someone whose sleep onset timing moved at least 30 minutes earlier.
Among participants receiving HETLIOZ, 60%, or 12 out of 20, achieved this level of improvement.
In the placebo group, 15%, or 3 out of 20, achieved a sleep timing advance of at least 30 minutes.
The difference was statistically significant, with a p-value of 0.008.
Because this was an exploratory analysis, the result provides additional information about the treatment response but is separate from the study's primary endpoint.
Safety Results Were Consistent With the Existing Label
Vanda said safety during the 28-day controlled treatment period was consistent with the established HETLIOZ label.
No new safety signals were identified during the study.
HETLIOZ already has an established safety profile from its approved uses.
The company plans to include the new DSWPD data in its discussions with the FDA.
How Does HETLIOZ Work?
HETLIOZ contains tasimelteon, which is a dual melatonin receptor agonist.
It activates the MT1 and MT2 melatonin receptors.
These receptors are involved in the body's regulation of circadian rhythms, which are the approximately 24-hour biological cycles that influence sleep and wakefulness.
Because DSWPD involves a delayed internal body clock, a medicine that acts on these pathways may help shift sleep timing.
HETLIOZ is therefore being evaluated as a treatment that can influence the timing of the body's sleep-wake cycle rather than simply acting as a conventional sleeping medicine.
HETLIOZ Already Has Two FDA-Approved Uses
HETLIOZ is not a new medicine.
The FDA first approved it in 2014 for the treatment of Non-24-Hour Sleep-Wake Disorder in adults.
In 2020, the FDA also approved HETLIOZ for nighttime sleep disturbances associated with Smith-Magenis Syndrome.
The proposed DSWPD indication would represent a third use for the same 20 mg dose.
HETLIOZ is also available as HETLIOZ LQ oral suspension for certain pediatric patients with Smith-Magenis Syndrome.
The medicine is not currently approved for DSWPD.
Vanda Plans to Submit an sNDA
Following the positive Phase III results, Vanda plans to submit an sNDA to the FDA for HETLIOZ in DSWPD.
The application is expected to include the new Phase III study as well as earlier studies conducted in related circadian rhythm disorders.
Vanda also plans to include more than a decade of experience with HETLIOZ from its two existing approved indications.
The FDA will review the submitted evidence before deciding whether to approve the new indication.
What Vanda Says About the Results
Mihael H. Polymeropoulos, M.D., president, CEO and chairman of the board of Vanda Pharmaceuticals, said people with DSWPD often remain undiagnosed and undertreated.
He said the Phase III study adds to the company's understanding of HETLIOZ as a circadian regulator.
Polymeropoulos also said Vanda looks forward to discussing the results with the FDA and pursuing a new indication for DSWPD.
What Happens Next?
Vanda's next step is to discuss the Phase III results with the FDA and prepare the planned supplemental application.
The company will use the Phase III results, previous studies and long-term experience with HETLIOZ to support its application.
For now, HETLIOZ remains FDA-approved for Non-24-Hour Sleep-Wake Disorder in adults and nighttime sleep disturbances associated with Smith-Magenis Syndrome.
Its use for DSWPD remains investigational until and unless the FDA grants approval for the proposed indication.
