DAYVIGO’s Promise at AAN 2024: Elevating Morning Alertness and Sleep Quality in Insomnia

• DAYVIGO (lemborexant) is an orexin receptor antagonist approved for treating adult patients with insomnia, who experience challenges with sleep onset and/or maintenance. It has received approval for insomnia treatment in over 15 countries, such as Japan, the United States, Canada, Australia, and various Asian nations.
• DAYVIGO functions by inhibiting the activity of a neurotransmitter in the brain known as orexin, which is believed to be involved in signaling the brain to awaken. Inhibiting the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is believed to dampen the drive to stay awake.
• Eisai Inc. presented studies on DAYVIGO (lemborexant), at the American Academy of Neurology Annual Meeting – 2024, highlighting its benefits for insomnia patients, including improved daytime alertness and sleep quality, particularly in older adults.

At the 2024 American Academy of Neurology Annual Meeting, Eisai Inc. presented ground-breaking research on DAYVIGO (lemborexant), showcasing its efficacy in addressing insomnia-related issues. Two posters were highlighted, one focused on the improvement of morning alertness in subjects with insomnia disorder, revealing significant increases in alertness ratings and a greater proportion of subjects shifting towards alertness after treatment with DAYVIGO compared to placebo. Another poster detailed the response and remission rates of DAYVIGO in older adults with insomnia and objective short sleep, demonstrating substantial improvements in sleep outcomes.

Specifically, in Phase III Study E2006-G000-304 (Study 304; NCT02783729), which analyzed the impact of lemborexant on daytime sleepiness/alertness, subjects receiving lemborexant showed a notable increase in alertness ratings compared to those on placebo, with a significant proportion experiencing a shift from mild/moderate sleepiness towards alertness. Additionally, a post-hoc analysis indicated that more subjects who reported sleepiness at baseline reported improved morning alertness during the last week of lemborexant treatment versus placebo. 

Study 304, a 1-month randomized controlled study in adults aged ≥55 years, included subjects receiving placebo (PBO), LEM 5mg (LEM5) or 10mg (LEM10), or zolpidem tartrate 6.25mg. A daily sleep diary assessed morning sleepiness/alertness, rated from 1 (extremely sleepy) to 9 (extremely alert). The analysis included changes from baseline sleepiness and the proportion of subjects shifting from mild/moderate sleepiness (≤3) towards greater alertness (4, 5, or >5).

At baseline, 206/743 (27.7%) of subjects reported mild/moderate sleepiness (PBO, n = 60; LEM5, n = 68; LEM10, n = 78). Change from baseline in alertness ratings increased significantly in the first 7 mornings with LEM5 and LEM10 compared with PBO (respective least squares mean treatment difference: 0.67 and 0.51). The proportion of subjects shifting from mild/moderate sleepiness towards alertness was greater with LEM5 (37%, 57%), LEM10 (41%, 55%) versus PBO (2%, 26%) across the first and last 7 mornings, respectively.

Additionally, a significant number of patients achieved remission and responded favorably to treatment, with response rates significantly higher compared to placebo. Baseline PSGs were obtained during a single-blind PBO run-in, followed by paired PSGs on Nights 1/2 and Nights 29/30. Responders were defined as subjects with ISI-TS ≥7 points decrease from baseline to end of treatment, while remitters achieved ISI-TS <8 points.

Of the PBO/LEM group subjects, 525/743 (70.7%) were in the I-SSD subgroup. For LEM5, 100/178 (56.2%) were responders, and 50/178 (28.1%) were remitters. For LEM10, 97/180 (53.9%) were responders, and 50/180 (27.8%) were remitters. For PBO, 58/138 (42.0%) were responders and 20/138 (14.5%) were remitters. The responder and remitter rates for LEM5 and LEM10 were significantly higher than those for PBO (all P<0.05). LEM was well tolerated, with most treatment-emergent adverse events being mild/moderate in severity.

Conclusion: 

The findings highlight DAYVIGO’s potential for improving sleep quality and daytime functioning in individuals with insomnia. Lemborexant treatment showed significant improvement in morning alertness without exacerbating sleepiness, indicating its promise as a therapeutic option. Additionally, older adults with objective short sleep duration (I-SSD) experienced clinically meaningful benefits with lemborexant, suggesting its efficacy even in challenging cases.

These findings underscore DAYVIGO’s potential as a promising therapeutic option for individuals grappling with insomnia, offering hope for enhanced sleep quality and daytime functioning.