[Preclinical and clinical efficacy of orexin receptor antagonist Lemborexant (Dayvigo®) on insomnia patients]

Nihon Yakurigaku Zasshi. 2021;156(2):114-119. doi: 10.1254/fpj.20093.
[Article in Japanese]

Abstract

Orexin receptor antagonists have been approved for insomnia, and the insomnia pharmacotherapy is being greatly progressed. Orexin is a neuropeptide produced in the lateral hypothalamic area, and its physiological role has been suggested to be a key mediator controlling the sleep-wake state. Orexin receptor antagonists are thought to induce physiological sleep by acting specifically on the sleep-wake cycle. Lemborexant is a dual antagonist acting on both two orexin receptors, the orexin 1 (OX1R) and 2 receptor (OX2R), with stronger inhibitory effects on OX2R. Since it binds to and dissociates from orexin receptors rapidly, the pharmacokinetics of its blood concentration may have an impact on its pharmacological action. In rats, lemborexant exhibited a sleep-inducing effect without altering sleep architecture. In the phase III studies in patients with insomnia, lemborexant significantly improved difficulties in falling asleep and maintaining sleep. While somnolence occurred as treatment-related adverse events in a dose-dependent manner, lemborexant was generally well-tolerated. Also, the effects on body sway and driving skills 8-9 hours after administration did not differ from those in the placebo group, suggesting little next morning residual effects. Subgroup analysis has shown that efficacy and safety of lemborexant were similar in patients with insomnia with comorbidities, suggesting lemborexant may also be useful for those patients. Based on the above results and others, lemborexant has been approved for the indication of insomnia in January 2020 in Japan. Lemborexant will give a new treatment option for patients with insomnia.

MeSH terms

  • Animals
  • Humans
  • Japan
  • Orexin Receptor Antagonists* / therapeutic use
  • Orexin Receptors
  • Pyridines
  • Pyrimidines
  • Rats
  • Sleep Initiation and Maintenance Disorders* / drug therapy
  • Treatment Outcome

Substances

  • Orexin Receptor Antagonists
  • Orexin Receptors
  • Pyridines
  • Pyrimidines
  • lemborexant