The drug was associated with significant improvements in sleep onset, sleep efficiency, and wake-after-sleep onset for both doses compared with placebo.
Lynn Kramer, MD
Findings from the phase 3 SUNRISE 1 study (Dayvigo; Eisai) demonstrate a significant improvement in sleep onset and sleep maintenance, including during the second half of the night, with treatment with lemborexant compared with both placebo and zolpidem tartrate in patients with insomnia.1
The small molecule orexin receptor antagonist was recently approved by the FDA for the treatment of insomnia in adults and will be available in 5 mg and 10 mg doses.2 The approval was based on data from the program’s 2 pivotal phase 3 trials, SUNRISE 1 and SUNRISE 2; the former is discussed in detail below.
SUNRISE 1 (NCT02783729) was a randomized, placebo- and active comparator-controlled, double-blind study that compared the safety and efficacy of lemborexant , placebo, and zolpidem tartrate. Patients were randomly assigned to lemborexant 5 mg (n=266) or 10 mg (n=269), 6.25 mg of zolpidem tartrate extended release (n=263), or placebo (n=208) for 1month at bedtime.
Using data collected from polysomnograms from the first 2 and last 2 nights of treatment, investigators assessed the change from baseline in latency to persistent sleep for lemborexant compared with placebo. Additional secondary end points included changes from baseline in sleep efficiency and wake-after-sleep onset compared with placebo, and wake-after-sleep onset in the second half of the night results compared with zolpidem.
Those enrolled in the trial were at least 55 years of age and met all Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for insomnia disorder. Additionally, patients had an Insomnia Severity Index (ISI) of >13 and had a history of subjective wake after sleep onset of typically >60 minutes on at least 3 nights per week in the previous 4 weeks prior to enrollment. Of the 1006 participants observed, 869 (86.4%) were women and the median age was 63 (range, 55-88 years).
On nights 29 and 30 at the end of month 1, investigators reported that both doses of lemborexant demonstrated significantly greater decreases from baseline on objective sleep onset compared with placebo (primary end point for least squares geometric means [LSM] treatment ratio vs placebo: for lemborexant 5 mg, 0.77; 95% CI, 0.67-0.89; P < .001; lemborexant 10 mg, 0.72; 95% CI, 0.63-0.83; P < .001). Additionally, patients treated with lemborexant had a significantly greater mean change from baseline in sleep efficiency compared with placebo (LSM treatment difference vs placebo for lemborexant 5 mg, 7.1%; 95% CI, 5.6%-8.5%; P < .001 and lemborexant 10 mg, 8.0%; 95% CI, 6.6%-9.5%; P < .001) and wake-after-sleep onset (LSM treatment ratio vs placebo for lemborexant 5 mg, −24.0 min; 95% CI, −30.0 to −18.0 min; P < .001; lemborexant 10 mg, −25.4 min; 95% CI, −31.4 to −19.3 min; P < .001)
Compared with patients who received zolpidem, those who received lemborexant had significantly greater decreases in wake-after-sleep onset results in the second half of the night (least squares mean treatment difference vs zolpidem for lemborexant 5 mg, −6.7 min; 95% CI, −11.2 to −2.2 min; P =.004 and for lemborexant 10 mg, −8.0 min; 95% CI, −12.5 to −3.5 min; P < .001).
Similar rates of treatment-emergent adverse events (TEAEs) were recorded across all 4 groups (range 25.4%-35.4%). The most common TEAEs were headache (placebo, 6.2%; zolpidem 6.25 mg, 5.3%; lemborexant 5 mg, 6.4%, lemborexant 10 mg, 4.9%) and somnolence (placebo, 1.9%, zolpidem 6.25 mg, 1.5%; lemborexant 5 mg, 4.1%; lemborexant 10 mg, 7.1%). There were 6 serious TEAEs observed, though none were treatment-related. Ultimately, 14 patients discontinued the study due to a TEAE.
"We believe the approval of Dayvigo is particularly exciting because it is the first FDA-approved medication to report safety data over a 12-month period along with sleep onset and sleep maintenance efficacy data over a six-month period in a pivotal clinical study," said Lynn Kramer, MD, Chief Clinical Officer, Neurology Business Group, Eisai, in a statement.2 "We look forward to making this new therapeutic option available to the millions of patients who suffer with insomnia.”
1. Rosenberg R, Murphy P, Zammit G, et al. Comparison of lemborexant with placebo and zolpidem tartrate extended release for the treatment of older adults with insomnia disorder. JAMA Netw Open. 2019;2(12):e1918254. doi:10.1001/jamanetworkopen.2019.18254.
2. US FDA approved Eisai’s Dayvigo (lemborexant) for the treatment of insomnia in adult patients [news release]. Woodcliff Lake, NJ: Eisai Inc. December 23, 2019. eisai.mediaroom.com/2019-12-23-U-S-FDA-Approves-Eisais-DAYVIGO-TM-lemborexant-for-the-Treatment-of-Insomnia-in-Adult-Patients. Accessed December 23, 2019.