Key Takeaways
Extended Takeaways
- Across pooled subjective outcomes at month 1, lemborexant 5 mg and 10 mg produced NNT values versus placebo < 10 for ISI score < 10, ISI score ≤ 7, ISI score ≥ 6-point decrease from baseline, and sTST > 80-minute increase from baseline, whereas pooled daridorexant 25 mg and 50 mg had no NNT values versus placebo < 10.
- A dose-response signal was seen with both agents but was clearer for lemborexant: for sTST improvement > 80 minutes, the NNT versus placebo was 7 with lemborexant 10 mg and 13 with lemborexant 5 mg, and somnolence also increased with dose (NNH 15 for 10 mg and 28 for 5 mg at month 1).
- For objective sleep maintenance, lemborexant showed particularly strong short-term effects, with NNT = 5 for ≥ 50% WASO improvement for both 5 mg and 10 mg in SUNRISE 1; PSG-based LPS improvement was more similar between drugs than subjective measures.
- Month 3 tolerability favored daridorexant for common sedating adverse events: pooled daridorexant 25-mg and 50-mg doses had NNH = 49 for fatigue and NNH = 85 for somnolence, compared with pooled lemborexant NNH = 29 for fatigue and NNH = 12 for somnolence.
- Discontinuation due to an adverse event was uncommon with both drugs, but the indirect comparison was influenced by placebo rates: pooled daridorexant studies had higher discontinuation rates in placebo than active treatment, leading to an imputed NNH of 1,000 for LHH calculations, while pooled lemborexant month 3 data yielded NNH = 52 [NS].
- Interpret indirect efficacy comparisons cautiously because the trial populations were not matched: SUNRISE 1 enrolled older adults ≥ 55 years or ≥ 65 years with ISI score ≥ 13 and mean baseline LPS 44.6–44.9 minutes, whereas daridorexant studies enrolled adults ≥ 18 years with ISI score ≥ 15 and mean baseline LPS 63.6–71.8 min.
