BOSTON—Results from two phase III trials indicate that the investigational oral medicine suvorexant may improve sleep initiation and maintenance in patients with insomnia, as reported at the 26th Annual Meeting of the Associated Professional Sleep Societies.
In one trial, patients with insomnia who took suvorexant for three months entered into continuous sleep 36 minutes sooner than they had before treatment began, compared with 26.6 minutes for patients who took placebo. Patients on suvorexant also spent 47.9 fewer minutes awake, compared with 25 minutes for patients who took a placebo.
After three months, no significant difference in sleep initiation was found between suvorexant and placebo in the second trial. On the other hand, patients spent 54.2 fewer minutes awake after three months of treatment with suvorexant than at baseline, compared with 24.8 minutes for patients who took placebo.
In the two multicenter, double-blind trials, 770 patients with primary insomnia were randomized to suvorexant, and 767 received placebo. Patients ages 18 to 64 received 40 mg of suvorexant, and patients older than 65 received 30 mg of the drug.
The trials’ end points included mean change from baseline for suvorexant, compared with placebo, in subjective and objective measures of sleep onset and maintenance. Subjective measures were made through patient reports, and objective measures were made through polysomnograph tests.
A Distinctive Mechanism of Action
Suvorexant’s mechanism of action differs from that of most current sleep therapeutics. The latter drugs target the gamma-aminobutyric acid (GABA) system, which plays a role in sleep, wakefulness, memory, and locomotor function.
By contrast, suvorexant operates on the orexin system, which is also known as the hypocretin system. The peptides orexin A and orexin B originate in the hypothalamus and promote arousal and wakefulness by binding with two orexin receptors, which have a localized distribution in the brain.
Suvorexant targets the orexin receptors to block the wakefulness signal from the orexin peptides and enable sleep initiation. If suvorexant were to receive approval from the FDA, it would be the first orexin receptor antagonist to be marketed.
No Serious Drug-Related Adverse Events
In the first trial, 25.1% of patients who took suvorexant reported experiencing adverse events, compared with 13.8% of patients on placebo. The rates of reported adverse events in the second trial were 22.2% for suvorexant and 16.4% for placebo. Investigators observed no differences in the incidence of serious drug-related adverse events between patients treated with suvorexant and those treated with placebo in either trial. The most common adverse events were sleepiness and headache.
In the first trial, 4.7% of patients taking suvorexant discontinued the medication because of an adverse event, compared with 6% of patients taking placebo. Rates of discontinuation due to adverse events in the second trial were 4.7% for suvorexant and 4.4% for placebo.
Suvorexant was not associated with statistically significant, next-day, objective residual effects, compared with placebo, as measured by the Digit Symbol Substitution Test. After three months in the first trial, 10.7% of patients taking the drug reported next-day sleepiness, compared with 3.4% of patients taking placebo. In the second trial, 10.3% of patients taking suvorexant reported next-day sleepiness, compared with 3.1% of patients on placebo. Cataplexy was not reported in either study.
—Erik Greb