Actelion: Orexin receptor antagonist shows successful proof-of-concept

Actelion has announced that ACT-078573, its orexin-OX1/OX2 receptor antagonist, has met its primary endpoint in a proof-of-concept study investigating administration of the drug to patients with primary insomnia.

These patients showed an improvement in sleep efficiency measured by Polysomnography, an objective measurement of sleep architecture – the amount of time spent in different stages of sleep.

Orexins are neuropeptides produced by dedicated neurons in the hypothalamus that are involved in maintaining wakefulness. ACT-078573 is an orally administered orexin receptor antagonist that induced a temporary and reversible blockade of the OX1 and OX2 receptors.

Isaac Kobrin, head of clinical development at Actelion, said: “This finding exceeds our expectations. The magnitude of the observed effect clearly demonstrates that the orexin system plays a key role in insomnia patients.”

He added that patients administered with ACT-078573 slept longer during the night than those who did not, while the compound could also improve sleep efficiency – the ratio of sleeping time against the time a patient is in bed.

This announcement follows the publication last week of pre-clinical and clinical data in Nature Medicine showing that ACT-078573 can induce signs of sleep in animal models in addition to man.