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New SUNRISE 2 data show a subjective, dose-dependent, and disease severity-dependent benefit with the insomnia therapy.
Patients with severe insomnia treated with lemborexant (DAYVIGO) achieved notably greater change in sleep onset latency and wake after sleep onset from baseline versus placebo in a new 12-month, phase 3 trial.
In new post-hoc analysis data presented at the Associated Professional Sleep Societies (SLEEP) 2022 Annual Meeting this week, a team of Eisai-supported investigators observed that the oral dual orexin antagonist therapy provided subjective, and somewhat dose-dependent, improvement in patients who previously had clinically meaningful reductions on the Insomnia Severity Index (ISI).
Led by Thomas Roth, PhD, director of the Sleep Disorders and Research Center at Henry Ford Hospital, investigators assessed the patient-reported outcomes on ISI in those with reductions of ≥7 points from the phase 3 SUNRISE 2 trial assessing lemborexant versus placebo in adults with insomnia disorder.
SUNRISE 2 was a 12-month, randomized, double-blind, partially placebo-controlled, parallel assessment including participants with ISI total scores ≥15 at baseline—indicating moderate to severe insomnia. Lemborexant was approved by the US Food and Drug Administration (FDA) at 5 mg and 10 mg doses for the treatment of insomnia disorder in adults in December 2019, on the strength of the SUNRISE trial program.
A total of 949 trial participants received either 5 mg or 10 mg lemborexant, or placebo for 6 months before being switched to therapy for the latter 6 months. Roth and colleagues conducted their post-hoc assessment with consideration to the trial’s first 6 months.
Investigators assessed for changes from baseline in subjective sleep-onset latency (SOL) and wake after sleep onset (WASO) versus placebo in the full analysis set, as well as in patients with severe insomnia per ISI total scores ≥22. They used a mixed-effect model repeated for measurement analysis.
Investigators observed 450 trial participants with ISI response at 6 months, across each treatment arm:
Among the treatment arms, 46, 48 and 29 had severe insomnia, respectively.
Among the full analysis set, the team observed a significantly greater change in subjective SOL from baseline in patients administered 5 mg lemborexant (-21.8) or 10 mg lemborexant (-28.2) than placebo (-11.4; P <.001). A similar decrease was observed among ISI-responder patients with the 5 mg (-26.7; P <.01) and 10 mg doses (-32.6; P <.001) versus placebo (-18.0).
Among ISI responders with severe insomnia, greater change in median subject SOL from baseline was observed among those who received 10 mg lemborexant (-41.4) versus placebo (-32.1; P <.05).
Mean change in subjective WASO from baseline among the full analysis set was -46.8 among 5 mg dose patients (P <.001), -42.0 among 10 mg dose patients (P <.05), and -29.3 among placebo recipients. Among ISI responders, change in subjective WASO was significantly greater among patients receiving 5 mg lemborexant (-58.9; P <.01) versus placebo (-43.6); however, patients receiving 10 mg lemborexant also improved in subjective WASO (-52.7; P <.05).
ISI responders with severe insomnia treated with 5 mg lemborexant again fared better (-91.6; P <.05) versus placebo (-70.2).
The team concluded with observations from the dose-related, disease severity-related, patient-subjective outcome interpretation of the SUNRISE 2 assessment of lemborexant.
“Insomnia severity index responders including those from the severe insomnia subgroup reported greater CFB in subjective sleep-onset latency and subjective wake after sleep onset than the full analysis set that was somewhat dose dependent,” they concluded. “Lemborexant generally showed benefit versus placebo.”
The study, “Subjective Sleep Outcomes with Lemborexant Among Subjects with Insomnia and Clinically Meaningful Decreases on the Insomnia Severity Index,” was presented at SLEEP 2022.