Barbara Boughton

June 18, 2013

SAN FRANCISCO — A phase 3 trial of a new drug called tasimelteon (Vanda Pharmaceuticals) improves the symptoms of a debilitating circadian-rhythm sleep disorder that frequently affects the blind.

"This is the first drug that can reset the circadian clock," said lead researcher Steven Lockley, PhD, a neuroscientist and associate professor of medicine at Harvard Medical School, Boston, Massachusetts.

In the study, blind patients with circadian-rhythm sleep disorder who took tasimelteon had improvements in the overall quantity of their nighttime sleep, as well as a reduction in daytime sleepiness, according to the research presented here at ENDO 2013: the Endocrine Society 95th Annual Meeting.

Vanda Pharmaceuticals filed for Food and Drug Administration (FDA) approval of tasimelteon in late May for non-24-hour sleep-wake disorder in the blind, according to Dr. Lockley. This is an orphan drug indication, in both the United States and European Union.

Melatonin Agonist That Resets the Circadian Clock

In many totally blind people, the normal circadian clock, which is set by the light-dark cycle over 24 hours, is disturbed. Called non-24-hour sleep-wake disorder, the condition can result in significantly reduced sleep time and sleep quality at night and problems with sleepiness during daylight hours.

In the Safety and Efficacy of Tasimelteon study (SET), 84 totally blind individuals from 27 US and 6 German medical centers were randomly assigned to receive either 6 months of tasimelteon at a dose of 20 mg daily or placebo.

Tasimelteon is a melatonin agonist that targets the same receptors as melatonin. In the study, significantly more patients who received tasimelteon were able to "reset" their circadian clock compared with placebo (20% vs 3%). Those on tasimelteon were also more likely to sleep during nighttime rather than daytime hours, with an average of 57 minutes of additional sleep each night.

Each patient was asked to take their medication 1 hour before initiating sleep. Starting 2 weeks after the start of the trial, patients were regularly assessed for changes in sleep quality and sleep time for up to 6 months. Clinicians also evaluated changes in symptoms such as fatigue and daytime sleepiness with the Clinical Global Impression of Change scale.

Significantly more patients on tasimelteon (24%, P < .05) showed improvements in symptoms that usually accompany sleep disruption, such as fatigue, but side effects for both the drug and placebo, including nausea and headache, were similar.

"Often non-24-hour sleep-wake disorder is misdiagnosed because patients just report sleepiness when they see their physician," Dr. Lockley said. The result is that blind patients with the disorder are prescribed a hypnotic or stimulant for insomnia.

"That's really not treating the disorder appropriately for the real problem — the desynchronized circadian clock," he noted.

Previous studies have suggested that tasimelteon might also be useful in treating transient disturbances in the sleep-wake cycle such as those caused by jet lag and night-shift work.

"The medication will most likely be very important for blind people because socially you want to be on the same time as everyone else and alert at the same time," commented Anne Cappola, MD, an endocrinologist and associate professor of medicine at the University of Pennsylvania, Philadelphia, who was not involved with this study.

"As well as improving quality of life in blind people with circadian-rhythm disorders, the medication might have the potential for improvement in metabolic parameters such as obesity and onset of diabetes," she added.

The study was funded by Vanda Pharmaceuticals. Dr. Lockley and Dr. Cappola have reported no relevant financial disclosures.

ENDO 2013: The Endocrine Society 95th Annual Meeting. Abstract FP26-6, presented June 16, 2013.

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