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Insomnia Severity Index Responders Show Additional Benefits From Lemborexant

Disease Spotlight | <b>Disease Spotlight: Insomnia</b>

In subanalyses of ISI responders with chronic insomnia, those in the lemborexant 10-mg group demonstrated significantly greater changes from baseline in sleep onset latency compared with placebo.

Results from a post-hoc analysis of Study 303 (NCT02952820) evaluating lemborexant (Dayvigo; Eisai) in patients with insomnia showed that those who had clinically meaningful reductions on Insomnia Severity Index (ISI) scores, including patients with more chronic cases, reported greater changes from baseline in several outcome measures.1

Study 303 was a 12-month, placebo-controlled, double-blind phase 3 trial that included 949 individuals in the full analysis set (FAS) with moderate to severe insomnia who were randomized to either 5-mg lemborexant (n = 316), 10-mg lemborexant (n = 315), or placebo (n = 318). The study consisted of 2 periods, with period 1 being a 1:1:1 randomization for 6 months, and period 2 being a continuation of treatment for those assigned a dose of emborexant and a rerandomization to treatment for those previously on placebo for another 6 months.

Presented at the 2022 SLEEP Annual Meeting, June 4-8, in Charlotte, North Carolina, the analysis included 175, 151, and 124 patients on lemborexant 5-mg, 10-mg, and placebo, respectively, who had clinically meaningful reductions of at least 7 points on the ISI. These patients, considered ISI responders, were analyzed on measures such as sleep onset latency (sSOL) and Wake Time After Sleep (WASO) following 6 months of treatment using a mixed-effect model repeated measurement analysis.

Led by Thomas Roth, PhD, director of the Sleep Disorders and Research Center, Henry Ford Hospital, those in both the 5-mg (–21.8) and 10-mg (–28.2) lemborexant groups from the FAS demonstrated significantly greater CFB in median sSOL compared with those on placebo (–11.4; P <.001). This continued with ISI responders, where significantly greater decreases in sSOL were found with lemborexant (5 mg: –26.7; P <.01; 10 mg: –32.6; P <.001) than placebo (–18.0). In total, 46, 48, and 29 ISI responders on either lemborexant 5 mg or 10 mg or placebo, respectively, had severe insomnia. Here, patients in the lemborexant 10-mg group (–41.4), but not the 5-mg group (–32.9; P >.05) had greater CFB in median sSOL than those on placebo (–32.1; P >.05).

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In the FAS, least squares mean CFB in sWASO was –46.8 (SD, 3.7) in the lemborexant 5-mg group (P <.001) and –42.0 (SD, 3.7) in the 10-mg group compared with –29.3 (SD, 3.6) in the placebo group. Among ISI responders, CFB in sWASO was greater with lemborexant 10-mg (–52.7; SD, 4.0; P >.05) and significantly greater with lemborexant 5-mg (–58.9; SD, 3.]; P <.01) vs placebo (–43.6; SD, 4.4). In ISI responders from the severe insomnia subgroup, greater CFB was observed in the lemborexant 5-mg group (–91.9; SD, 9.5) vs placebo (–70.2; SD, 11.1; P >.5). Notably, the CFB for the lemborexant 10-mg group (–71.4; SD, 9.0) was similar to placebo.

Lemborexant, a small molecule orexin receptor antagonist, received approval to treat insomnia in 2019, and since then has been evaluated in several different analyses. At SLEEP 2021, an analysis from Study 303 suggested that a majority of patients on the drug experience a positive medication effect, as shown using Patient Global Impression–Insomnia (PGI-I) item scores. At month 9, more than 70% of those in both treatment arms (5 mg: 73.4% [177 of 241]; 10 mg: 76.3% [161 of 211]) reported that the therapy helped them sleep, with similar results at month 12 (5 mg: 74.6% [153 of 205]; 10 mg: 77.6% [149 of 192]). Additionally, the majority of patients reported that lemborexant increased total sleep time at both month 9 (5 mg: 62.2% [150 of 241]; 10 mg: 73.0% [154 of 211]) and month 12 (5 mg: 62.4% [128 of 205]; 10 mg: 65.1% [125 of 192]).2

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1. Roth T, Moline M, Pinner K, Yardley J, Pappadopulos E, Malholtra M. Subjective sleep outcomes with lemborexant among subjects with insomnia and clinically meaningful decreases on the insomnia severity index. Presented at: SLEEP Annual Meeting, 2022; June 4-8; Charlotte, NC. Abstract 0440
2. Drake C, Yardley J, Pinner K, Perdomo C, Moline M. Long-term Perception of Medication Effectiveness in Subjects Receiving Lemborexant for Up to 12 Months. Presented at: SLEEP 2021; Virtual; June 10-13, 2021. Poster 339.