ACTELION ANNOUNCES PUBLICATION OF DATA ON INSOMNIA TREATMENT

Actelion has announced the publication of Phase I and preclinical clinical data in the February edition of Nature Medicine. These data demonstrate that Actelion's Orexin-OX1/OX2 receptor antagonist ACT-078573 induces characteristic signs of sleep in animal models as well as in humans. In healthy human volunteers, signs of sleep -- such as reduced alertness -- were observed when ACT-078573 was administered during daytime.

Orexins are neuropeptides produced in the brain by a very small number of dedicated neurons located in the hypothalamus. Orexins play an important role in maintaining wakefulness and therefore regulate the sleep-wake cycle. ACT-078573 is the first oral orexin receptor antagonist that penetrates the blood-brain barrier and is capable of inducing a transient and reversible blockade of the two receptors, OX1 and OX2, according to the company.

In animal models, the administration of ACT-078573 resulted in an increase in rapid-eye-movement (REM) sleep. In contrast, the use of GABA-A receptor modulators such as zolpidem was associated with a decrease in REM sleep. REM is the specific sleep phase where dreams occur. REM sleep is assumed to play a key role in the consolidation of different types of memory function, according to Actelion.

The Phase I study was a randomized, placebo-controlled, double-blind, single-ascending-dose trial that enrolled 70 healthy male human subjects with no history of neurological, psychiatric or sleep disorders. Within one hour after taking a single dose of ACT-078573, patients displayed signs of sleep. Treatment was well tolerated up to 1,000 mg with no severe or serious adverse events reported. Signs of sleep disappeared after six hours with a dose of 400 mg.