The 24-hour rhythm in sleep and wakefulness is regulated by an intrinsic body clock residing in the suprachiasmatic nucleus (SCN) with the brain. The individual period of the endogenous clock is usually longer than 24 hours (average 24.2-hours) and is normally entrained (synchronized) by the daily light-dark cycle to match the environmental 24-hour day.

Non-24-hour sleep-wake disorder is characterized by (i) complaint of both insomnia and sleepiness (with impairment of social and occupational functioning during the daytime), (ii) a progressive delay of sleep, with the inability to maintain stable entrainment to a 24-hour sleep-wake cycle, and (iii) the presence of that sleep pattern for at least 6 weeks. The Non-24-hour sleep-wake disorder occurs in about two thirds of totally blind individuals and is very rare in the sighted population.

Totally blind individuals with Non-24-hour sleep-wake disorder encounter great difficulties to maintain a lifestyle that is within the societal norm. When forcing them into sleep at night they will experience periods of premature sleep onset with early awakenings, which culminate in reduced total sleep time, and sleep deprivation. Therefore successful therapy is expected to improve total night sleep time in these patients.

Circadin® has been classified by the U.S. FDA since July 2004 and by the EMEA since April 2005 as an orphan drug in development for the treatment of non-24-hour sleep-wake disorder in blind individuals without light perception.