Vanda to initiate tasimelteon Phase IIb/III clinical trial in Major Depressive Disorder

Vanda Pharmaceuticals Inc. (Nasdaq: VNDA) today announced its plans to initiate a Phase IIb/III clinical trial of tasimelteon in patients with Major Depressive Disorder (MDD).  The trial is expected to begin during the second half of 2011.  Tasimelteon is currently being evaluated in Phase III clinical trials for the treatment of Non-24-Hour Sleep/Wake Disorder (N24HSWD) in blind individuals without light perception.

"Research suggests that misalignment of the circadian rhythm, or body clock, may have significant health consequences, including those related to mood disorders such as major depression," said Mihael H. Polymeropoulos, M.D., Vanda's President and CEO.  "Treating depression with a circadian regulator is a novel concept, which has more recently become an area of focus for the pharmaceutical industry. Expansion of our investigations into MDD is consistent with our vision for Vanda as a leading specialty pharmaceutical company focused on the development and commercialization  of differentiated products for central nervous system disorders."

There is considerable evidence that suggests circadian rhythm disturbances are important in the pathophysiology of mood disorders. Depressed patients often show altered circadian rhythms, sleep disturbances, and diurnal mood variation. Chronotherapies, including bright light exposure, have been successfully used to treat seasonal and non-seasonal mood disorders. These observations suggest that aberrations of the circadian clock may significantly contribute to the production of the symptoms of MDD and therefore treatments that aim at restoring the regulation of the circadian clock could prove beneficial.

Despite the availability of a number of treatments for MDD, there remains a significant unmet medical need.  In the large Star*D study sponsored by the National Institute of Mental Health, it was shown that two thirds of patients continued to exhibit symptoms even after a course with currently available treatments.  In addition to this partial response to treatment, patients often experience a number of significant side effects including sexual dysfunction, insomnia and weight gain.

If successful, tasimelteon could add significant value to the treatment armamentarium for depression.  Its novel mechanism of action as a circadian regulator could address both the mood as well as the sleep disruption in patients with MDD, and at the same time offer a mild side effect profile.

The Vanda Phase IIb/III trial will investigate the efficacy and safety of tasimelteon versus placebo in the treatment of MDD. The study is expected to include an 8-week treatment period and an optional open-label extension. Vanda plans to assess the antidepressant and circadian effects of tasimelteon, as well as further characterize the safety profile of the compound.  

Tasimelteon and the Body Clock

Tasimelteon is a circadian regulator that binds to two high-affinity melatonin receptors, Mel1a (MT1R) and Mel1b (MT2R).  These receptors are found in high density in the suprachiasmatic nucleus of the brain (SCN), which is responsible for synchronizing an individual's sleep/wake cycle.  Tasimelteon is currently being evaluated for the treatment of N24HSWD, which is a chronic circadian rhythm sleep disorder (CRSD) that occurs when an individual is unable to synchronize their internal clock to the 24-hour light/dark cycle.  Tasimelteon may also have applications in other CRSDs, including Delayed Sleep Phase Disorder, Jet Lag and Shift Worker Sleep Disorder.