Vornorexant

ID: vornorexant

Aliases: TS-142, ORN-0829, Vorzzz

Type: compound

Route/form: oral dual orexin receptor antagonist in clinical/Japan insomnia context

Status: approved_in_japan_or_investigational_elsewhere

Evidence level: human RCT

Best data tier: human controlled/review

Support scope: human, non-human/mechanistic, review/regulatory

Source types: human_rct, human_trial, meta_analysis, preclinical, regulatory_review

Linked sources: 5

Broad outcomes: Brain / mood / sleep

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• orexin OX1 receptor antagonism
• orexin OX2 receptor antagonism
• sleep onset and maintenance

Optimization domains

• sleep
• insomnia
• orexin
• CNS
• sedation

Research basis

• A randomized double-blind phase 2 insomnia study found single-dose TS-142 improved PSG latency to persistent sleep and wake after sleep onset versus placebo.
• The short half-life/PK profile makes it a distinct DORA lead compared with longer-half-life agents like lemborexant.

Limits, risks, and missing evidence

• Most public evidence is still smaller and less mature than established DORAs such as suvorexant, lemborexant, and daridorexant.
• DORAs still require caution around next-day impairment, narcolepsy/hypersomnolence contexts, CNS depressants, and jurisdiction-specific approval/access.

Risk flags

• insomnia drug
• next day impairment
• CNS depressant caution
• narcolepsy caution
• jurisdiction specific approval
• limited long term data

Linked papers, labels, and reviews

1. Effects of TS-142, a novel dual orexin receptor antagonist, on sleep in patients with insomnia: a randomized, double-blind, placebo-controlled phase 2 study
   human_rct / pubmed_vornorexant_phase2_insomnia_2022
   Phase 2 crossover insomnia study; single oral doses improved PSG sleep latency and wake after sleep onset versus placebo.
2. Pharmacokinetics, pharmacodynamics and safety profile of the dual orexin receptor antagonist vornorexant/TS-142 in healthy Japanese participants
   human_trial / pubmed_vornorexant_phase1_pk_2023
   Randomized double-blind placebo-controlled phase 1 single/multiple-dose PK/PD and safety studies in healthy Japanese participants.
3. Preclinical metabolism and the disposition of vornorexant/TS-142, a novel dual orexin 1/2 receptor antagonist for the treatment of insomnia
   preclinical / pubmed_vornorexant_preclinical_metabolism_2024
   Preclinical metabolism/disposition paper; useful for half-life and PK rationale.
4. Japan approvals include Vorzzz (vornorexant) for insomnia
   regulatory_review / pharmajapan_vornorexant_approval_2025
   Trade/regulatory news noting Japan MHLW approval of Taisho's vornorexant insomnia therapy in August 2025.
5. Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis
   meta_analysis / pubmed_dora_network_meta_2023
   Systematic review/network meta-analysis for DORAs in insomnia; provides class context for vornorexant comparisons.