Phase 1b/2 Data Show Investigational HS-10506 Reduces Sleep Latency in Insomnia

Data from a phase 1b/2 randomized trial presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18-22 in Chicago, Illinois, showed that HS-10506 (Hansoh Pharma) significantly reduced sleep latency and improved multiple sleep parameters in adults with insomnia, with a favorable safety and pharmacokinetic profile.¹

Presented by Yuping Wang, MD, Professor and Chief Physician, Department of Neurology, Xuanwu Hospital, the study evaluated HS-10506, a highly selective orexin-2 receptor (OX2R) antagonist, in a multicenter, double-blind, placebo-controlled trial (NCT06279286).¹ Orexin signaling is a key regulator of wakefulness, and selective antagonism of OX2R has emerged as a targeted strategy to promote sleep while potentially minimizing off-target effects seen with broader sedative agents.²

The trial included both a phase 1b dose-escalation component and a larger phase 2 efficacy cohort. In phase 1b, 32 patients were randomized 3:1 to receive HS-10506 or placebo across ascending doses ranging from 10 mg to 80 mg to assess safety and pharmacokinetics. In phase 2, 238 patients were randomized to receive once-nightly HS-10506 at doses of 20 mg, 40 mg, or 60 mg, or placebo, over a 28-day treatment period.¹ The primary endpoint was change from baseline in polysomnography-measured latency to persistent sleep (LPS) at days 13 and 14.¹

Results from the phase 2 portion demonstrated statistically significant and dose-dependent reductions in LPS with HS-10506 compared with placebo. Mean reductions were –13.7 minutes (95% CI, –21.0 to –6.4; P < .001) with the 20 mg dose, –16.6 minutes (95% CI, –23.8 to –9.3; P < .001) with 40 mg, and –18.8 minutes (95% CI, –26.1 to –11.6; P < .001) with 60 mg.¹

In addition to effects on sleep latency, HS-10506 demonstrated consistent improvements across both objective and subjective sleep measures, indicating broader benefits on sleep architecture and patient-reported outcomes.¹ The treatment effects were sustained over the 28-day study period, supporting the potential for ongoing efficacy with continued use.

From a safety standpoint, HS-10506 was generally well tolerated across both study phases. Treatment-emergent adverse events occurring in at least 5% of patients included somnolence and urinary tract infection, with no apparent dose-limiting safety concerns.¹ Notably, the study reported no significant negative effects on alertness, cognition, mood, or anxiety, and no evidence of rebound insomnia following treatment discontinuation.²

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Pharmacokinetic findings from the phase 1b portion showed that HS-10506 was rapidly absorbed and eliminated following oral administration, with no significant accumulation after repeated dosing. These characteristics may support its use as a once-nightly therapy with minimal next-day residual effects.¹

These findings build on earlier phase 1a data presented at the 2024 European College of Neuropsychopharmacology Congress, which demonstrated that HS-10506 was safe and well tolerated in healthy participants, with dose-dependent increases in somnolence consistent with its pharmacologic mechanism. In that study, the agent showed rapid absorption, with a median time to maximum concentration of 0.5 to 1.0 hours and a terminal half-life of approximately 2 to 5 hours.³

Collectively, the phase 1b/2 results further support the role of selective OX2R antagonism as a targeted approach for insomnia management. Unlike dual orexin receptor antagonists currently available, HS-10506 selectively inhibits OX2R, which may allow for sleep promotion while preserving other physiologic functions mediated by OX1R.²

As the insomnia treatment landscape continues to evolve, these data suggest that HS-10506 may represent a promising next-generation therapy with a favorable balance of efficacy, tolerability, and pharmacokinetic properties. Larger phase 3 trials will be needed to confirm these findings and better define its role in clinical practice.¹

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REFERENCES
1. Wang Y, Huang Z, Xu Q, et al. Safety, efficacy and pharmacokinetics of HS-10506 in insomnia patients: a randomized, double-blind, placebo-controlled, phase 1b/2 study. Presented at: 2026 American Academy of Neurology Annual Meeting; April 18–22, 2026; Chicago, IL.
2. Hansoh Pharma. HS-10506 study data presented at AAN 2026. News release. April 17, 2026. https://www.hspharm.com/news/news-detail-513444.htm
3. Li Y, Li H, et al. A randomized, double-blind, placebo-controlled, single ascending dose study of HS-10506 in healthy subjects. Presented at: 37th ECNP Congress; September 2024.