Dayvigo for insomnia has favorable benefit-risk ratio

Dayvigo for the treatment of insomnia had a favorable benefit-risk ratio as assessed by three measures, according to an analysis of phase 3 trials published in Journal of Clinical Psychiatry.

Measures used for Dayvigo (lemborexant, Eisai) included number needed to treat, number needed to harm and likelihood to be helped or harmed.

“Lemborexant, a dual orexin receptor antagonist (DORA), has been approved by the [FDA] for the treatment of adult patients with insomnia (as characterized by difficulties with sleep onset and/or sleep maintenance) and is also available in Japan and Canada,” Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, and colleagues wrote. “The mechanism of action of DORAs, which attenuate excessive wakefulness/arousal signaling, differs from that of hypnotic agents such as -aminobutyric acid (GABA)-A receptor agonists (for example, the benzodiazepine temazepam and the non-benzodiazepine zolpidem) and others (for example, the melatonin receptor agonist ramelteon) that augment sleep signaling.”

The researchers aimed to describe Dayvigo for treating DSM-5 insomnia in adults according to the three measures using Dayvigo data from two phase 3 trial conducted between 2016 and 2018. They assessed efficacy using different categorical definitions for response and they assessed tolerability via an evaluation of rates of adverse events. They made direct comparisons with zolpidem extended release and indirect comparisons with other hypnotic agents, such as suvorexant, doxepin, ramelteon, zolpidem immediate release, eszopiclone, zaleplon, and selected benzodiazepines using data from published reports and regulatory documents.

Results showed Dayvigo had a clinically relevant magnitude of therapeutic effect according to number needed to treat values vs. placebo as robust as three. Overall, number needed to harm values for Dayvigo vs. placebo were 10 or greater, which suggested the drug’s relative tolerability. Somnolence represented the most common adverse event, with number needed to harm estimates of 28 for Dayvigo 5 mg and 15 for Dayvigo 10 mg.

The researchers reported low discontinuation rates for Dayvigo because of an adverse event, and Dayvigo 5 mg had a lower rate than that for placebo. They noted a range of 13 to 54 for likelihood to be helped or harmed contrasting the statistically significant endpoint efficacy measures vs. discontinuation because of an adverse event. Dayvigo had generally more robust number needed to treat values compared with zolpidem extended release for the polysomnography and sleep diary outcomes. Number needed to treat data for the other hypnotics showed generally similar effect sizes to those for Dayvigo in indirect comparisons.

“Head-to-head trials among DORAs versus other hypnotics, as well as between [Dayvigo] and suvorexant, are desirable to better understand their similarities and differences in clinically relevant populations,” Citrome and colleagues wrote.