Positive Phase III Clinical Trial Results for Totally Blind Persons with Sleep Disorders

Photo of a clock face at 2:00 AM

On January 23, 2013, Vanda Pharmaceuticals, Inc. announced positive Phase III clinical trial results from the recently completed Randomized-withdrawal study of the Efficacy and Safety of Tasimelteon (RESET) study; in addition, on December 18, 2012, Vanda announced positive Phase III clinical trial results from the Safety and Efficacy of Tasimelteon (SET) study.

Tasimelteon is an experimental drug treatment for totally blind individuals with no light perception who experience a sleep problem called “Non-24-Hour Sleep-Wake Disorder.” In the United States, this disorder affects approximately 65,000 totally blind individuals who lack the light sensitivity necessary to reset their internal “body clocks.”

About Vanda Pharmaceuticals, Inc.

Vanda Pharmaceuticals, Inc. is a biopharmaceutical company in Rockville, MD that is working to advance the science of developing new medicines and use novel approaches to deliver these new medicines to individuals who can benefit from them. Primarily, Vanda is focused on the development and commercialization of products for the treatment of central nervous system disorders.

Non-24 Hour Sleep-Wake Disorder

Non-24 Hour Sleep-Wake Disorder (Non-24) is a serious, rare circadian rhythm disorder that affects a majority of totally blind individuals who lack light perception and cannot reset their master body clocks to the 24-hour day. At the present time, there is no FDA-approved treatment for Non-24. You can find more information about Non-24-Hour Sleep-Wake Disorder, including frequently-asked questions, news, and research updates at the 24SleepWake website.

Recent Clinical Trial Results

The SET Study

  • The SET study was an 84-patient randomized, double-masked, placebo-controlled study in subjects with Non-24, and the first of four clinical studies that comprise Vanda’s Phase III development program for tasimelteon. (Note: In research terminology, a placebo is a substance that has no therapeutic effect or contains no active medication, often used as a control when testing new drugs.)
  • Results from the SET study indicated that tasimelteon was safe, well-tolerated, and successfully reset the master body clock. In addition, tasimelteon significantly improved clinical symptoms across a number of sleep and wake measures, including total sleep time, nap duration, and the timing of sleep.

The RESET Study

  • The RESET study was a 20-patient randomized withdrawal study designed to demonstrate the maintenance effect of 20 mg. of tasimelteon. Initially, study subjects were treated with tasimelteon for three months; subjects who responded to tasimelteon during this phase, as measured by a “reset” of their circadian rhythms, were then randomized to receive either a placebo or continue receiving tasimelteon for two more months.
  • Results from the RESET study demonstrated the maintenance effect of 20 mg. of tasimelteon to reset circadian rhythms in individuals with Non-24. Subjects treated with tasimelteon maintained the “reset” of their body clocks, while subjects treated with a placebo showed significant deterioration in measures of nighttime sleep, daytime naps, and timing of sleep.

Vanda plans to submit a New Drug Application (NDA) for tasimeleton to the U.S. Food and Drug Administration (FDA) in mid-2013.

Tasimelteon and Non-24

From the Vanda Pharmaceuticals website:

Graphic of a tasimelteon molecule

Tasimelteon is an oral compound in development for sleep and mood disorders, including Circadian Rhythm Sleep Disorders (CRSD). Examples of CRSD include transient disorders, such as jet lag, and chronic disorders such as shift work sleep disorder and Non-24-Hour Sleep-Wake Disorder.

Tasimelteon has been shown to improve sleep parameters in prior clinical studies that simulated a [disruption] of the circadian clock. In two such studies, tasimelteon caused significant improvement in sleep onset and sleep maintenance without evidence of next-day residual effects.

On January 19, 2010, the FDA granted orphan drug designation status for tasimelteon in Non-24-Hour Sleep-Wake Disorder in blind individuals without light perception. The FDA’s Orphan Drug Designation program provides “orphan” status to drugs defined as those intended for the safe and effective treatment, diagnosis, or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.

Additional Study Results

From the 24SleepWake website:

  • Vanda has completed over 1,000 surveys of totally blind individuals with no light perception. Over 75% of participants taking the survey report one or more of the following: trouble falling asleep, staying asleep, staying awake, and/or difficulty with napping.
  • During the screening and diagnosis part of the trial, sleep diary information highlighted some of the sleep problems caused by Non-24. Over 50% of individuals with a Non-24 diagnosis have the equivalent of one night per month with almost no sleep, and almost 10% have the equivalent of one night per week with almost no sleep.
  • In addition to the severe sleep problems, Non-24 patients report daytime napping that comes and goes, depending upon where the body clock is set relative to the normal day. This napping is increased only when the body clock is out of alignment with the normal day/night cycle; those with Non-24 do not show increased napping at times when the body clock is aligned.

Comment from Vanda

From a Vanda Pharmaceutical announcement about the Phase III RESET results:

The RESET study demonstrates the efficacy of chronic treatment with tasimelteon in Non-24 and further supports the results of the SET study, which established the ability of tasimelteon to [reset] the master body clock and significantly improve the clinical symptoms of Non-24.

“We are excited by these results as they move us one step closer towards providing a treatment for blind individuals with Non-24,” said Mihael H. Polymeropoulos, M.D., President and CEO of Vanda.

Additional Non-24-Hour Sleep-Wake Information

For more information, you can visit the project website at www.non24registry.com; call 1-888-389-7033 (toll free) Monday-Friday, 9:00 AM to 5:00 PM EST; or send an email to info@non24registry.com.

Matilda Ziegler magazine has published an informative five-part series on Non-24-Hour Sleep-Wake Disorder by Lynne Lamberg, a science writer with expertise in the area of circadian rhythm biology.