Insomnia is the most prevalent sleep disorder — roughly 10-15% of adults meet chronic insomnia criteria — and the therapeutic landscape has been reshaped by dual orexin receptor antagonists (DORAs). Suvorexant (Belsomra), lemborexant (Dayvigo), and daridorexant (Quviviq) have set a new efficacy and safety bar that next-generation programs are chasing.
What the DORA precedent means for new sponsors
The DORA precedent gives sponsors a well-defined efficacy corridor: statistically significant improvements in latency to persistent sleep (LPS) and wake after sleep onset (WASO) on PSG at 1 and 3 months, paired with subjective total sleep time (sTST) and Insomnia Severity Index (ISI) improvements. Programs falling short on WASO reduction relative to daridorexant will struggle to differentiate.
PSG vs. sleep diaries — you need both
- PSG at baseline and 1/3-month follow-up for objective LPS/WASO.
- Consensus Sleep Diary daily throughout treatment for sTST and sleep quality.
- Actigraphy to bridge diary and PSG data and detect adherence issues.
- Next-day function — DSST, KSS, and driving simulation for morning residual effects (the DORA class's key safety differentiator).
Digital therapeutics as active comparators
CBT-I is guideline-recommended first-line therapy, and FDA-cleared digital CBT-I products (Somryst) are now realistic comparator arms. Combination studies (DORA + dCBT-I) are the frontier. Sponsors evaluating a digital arm should review our digital health CRO playbook for validating app-based endpoints and our SaMD clinical validation guide.
Enrollment reality
Insomnia trials look easy on paper — until PSG-verified screening rejects 40-60% of self-identified insomniacs for confounding OSA, PLMS, or insufficient sleep opportunity. Our sleep research CRO team stages a two-arm screening funnel (PSG + clinical interview) to keep the randomized population clean.