Most totally blind people live with circadian rhythms that are not synchronized with the 24-hour world, a disorder called non-24 hour sleep-wake rhythm disorder (non-24), which some patients describe as a disability worse than the blindness itself. The disorder, estimated to affect about 65,000-95,000 people in the U.S., is caused by an inability of light to reset their circadian pacemaker.
In a new research study led by Steven W. Lockley, PhD, Division of Sleep and Circadian Disorders, published in The Lancet, investigators describe two Phase 3 clinical trials, SET and RESET, for the drug tasimelteon (HETLIOZ), a dual melatonin receptor agonist. Tasimelteon treats the underlying circadian disorder to reset the circadian clock each day, rather than just treating the symptoms of insomnia or excessive sleepiness. These data were used to gain FDA approval in 2014 and recent approval this year by the European Medicines Agency (EMC) for the treatment of non-24-hour sleep-wake rhythm disorder in the blind.
Results of the research showed that a higher proportion of patients who received tasimelteon could successfully reset their circadian clock in addition to having more night-time and less daytime sleep. Specifically, patients who received tasimelteon had more sleep during the period of night-time when symptoms were the worst, which indicates a ‘setting’ of the circadian clock. Researchers were also able to perform a randomized withdrawal study, which indicated that continued daily treatment was necessary to maintain the correction to the circadian clock and that discontinuing the therapy resulted in a ‘resetting’ of the misaligned circadian clock.
“This study is a major breakthrough in the field not only for totally blind patients but also because tasimelteon is the first treatment approved for any disorder that relies on resetting of the circadian clock, as opposed to simply treating the symptoms of a circadian rhythm disorder, such as insomnia or excessive sleepiness,” said Lockley. “The demonstrated ability to train the body’s internal clock is also an important advance, as it introduces the concept of shifting or resetting the circadian clock as important in its own right to the medical community, in addition to symptomatic relief.”