Lemborexant bests placebo, zolpidem for insomnia in older adults

Takeaway

• Lemborexant, an investigational oral orexin receptor antagonist, outperformed placebo and zolpidem for improving objective measures of insomnia in older adults.

Why this matters

• Current pharmacotherapeutic options have adverse effects and limited effectiveness in this population.

Key results

• Change in log-transformed sleep latency (SL) vs placebo (least-squares geometric mean treatment ratio):
  • Lemborexant 5 mg: 0.77 (P<.001).
  • Lemborexant 10 mg: 0.72 (P<.001).
• Change in sleep efficiency vs placebo (least-squares mean [LSM] treatment difference):
  • Lemborexant 5 mg: 7.1% (P<.001).
  • Lemborexant 10 mg: 8.0% (P<.001).
• Change in wake-after-sleep onset (WASO) vs placebo (LSM treatment difference):
  • Lemborexant 5 mg: –24.0 minutes (P<.001).
  • Lemborexant 10 mg: –25.4 minutes (P<.001).
• Change in WASO in second half of night vs zolpidem (LSM treatment difference):
  • Lemborexant 5 mg: –6.7 minutes (P=.004).
  • Lemborexant 10 mg: –8.0 minutes (P<.001).
• Serious adverse events:
  • 4 patients in zolpidem group.
  • 2 patients in lemborexant 5 mg group.

Expert comment

• Authors of invited commentary note that no specific values were reported for sleep diary SL and WASO despite claims of statistically significant improvement.
• The lack of this information, they say, precludes understanding "how the variables that represent the patients’ presenting concerns were affected.”

Study design

• North American, European phase 3 randomized controlled trial: 1006 adults ages ≥55 years with confirmed insomnia disorder.
• Randomization: placebo vs zolpidem extended release (6.25 mg) vs lemborexant (5 or 10 mg) for 1 month at bedtime.
• Main outcome: polysomnographic SL for lemborexant vs placebo.
• Funding: Eisai.

Limitations

• Unknown long-term outcomes.
• Use of fixed-dose zolpidem.
• Differences between objective, subjective WASO.