Regulatory Decision Summary for Dayvigo

Dayvigo (lemborexant) is a dual receptor orexin antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. Regulatory authorization was based, in part, on two phase 3 pivotal efficacy and safety studies:

1. a 6-month, double-blind, randomized, placebo-controlled study in subjects 18 years or older (number of subjects (n) = 959), with a 6-month safety extension period, and
2. a double-blind, randomized, active- and placebo-controlled 1-month study conducted in females aged ≥ 55 years and males aged ≥ 65 years (n = 1,006).

Overall, the studies provided evidence of efficacy for Dayvigo, at both 5 milligrams (mg) and 10 mg doses, as measured by shorter time to sleep onset, improvement in sleep maintenance, and more time spent asleep compared to placebo. The results from these studies were statistically significant, clinically meaningful, demonstrated over an adequate study duration and supported by both objective (polysomnography) and patient-reported measures. Robustness of these findings were supported by responder analyses.

The elderly population (patients ≥65 years of age) was well represented with results that were generally consistent with the nonelderly population. Both Phase 3 studies had a much higher proportion of females to males, which is representative of the patient population.

The most frequently reported adverse event in the clinical program was somnolence. This occurred dose-dependently and was the most frequently reported reason for study discontinuations. There did not appear to be a difference in the safety profile based on age or sex of subjects. There also appeared to be a dose-related signal for parasomnias (such as confusional arousals, sleepwalking, sleep terrors, sleep-related eating disorders, sleep paralysis, nightmare disorder, exploding head syndrome, sleep-related hallucinations, somnambulism, and sleep enuresis) that occurred solely in the Dayvigo group. There were two incidences of potential complex sleep behaviors, which has been added to the Warnings and Precautions section of the Product Monograph (PM).

Dayvigo impaired middle of the night postural stability and worsened performance on tests of attention and memory. Next day driving may be affected in some individuals. A blinded independent adjudication committee evaluated events of cataplexy and seizure. There was one non-conclusive case of cataplexy and one patient who experienced seizure following administration of a 25 mg (supratherapeutic) dose. Abuse liability was similar to other sleep aids; however no evidence of abuse or diversion was observed.

Notable uncertainties include the effect of exposure to Dayvigo during pregnancy on the fetus, to infants of breast-feeding women, and in patients with severe hepatic impairment, moderate to severe obstructive sleep apnea or chronic obstructive pulmonary disease.

A Risk Management Plan (RMP) for Dayvigo was submitted to Health Canada. Upon review, the RMP was considered to be acceptable, with revisions and follow-up required.

The adverse events, risks and uncertainties have been labelled in the PM. The benefit-harm-uncertainty profile of Dayvigo is considered positive.

For more information on Health Canadas decision, please view the Summary Basis of Decision.