SEP-363856 · program

Ulotaront (SEP-363856) for Generalized anxiety disorder

Phase 2/3CompletedOtsuka Pharmaceutical Co., Ltd. (4578.T)

Indications for SEP-363856: Generalized anxiety disorder · Phase 2/3 Major depressive disorder · Phase 2/3

Phase 2/3 ulotaront monotherapy in generalized anxiety disorder (SEP361-226 / NCT05729373, n=434, HAM-A primary), completed 26 Sep 2025; topline pending. A Phase 2/3 adjunctive MDD program (NCT05593029, n=929) also completed (Nov 2025). Otsuka committed to continuing GAD/MDD development after the 2023 schizophrenia Phase 3 failure.

Development timeline

Phase 2/3Mar 2023 – Sept 2025
  1. Phase 2/3 GAD study (NCT05729373) reached completion; topline results not yet disclosed.
  2. Sumitomo Pharma amended its worldwide license; Otsuka took over ulotaront (incl. GAD/MDD) and decided to continue development.
  3. First patient randomized in the Phase 2/3 GAD study (NCT05729373).

Clinical trials in Generalized anxiety disorder

NCT05729373SEP361-226Phase 2/3Completedn=434

Phase 2/3 Study of SEP-363856 in Generalized Anxiety Disorder

Started Mar 2023· Primary completion Sept 2025· 📍 83 sites across 8 countries (United States, Japan, Bulgaria, Spain)

Formulations

FormulationRouteRegimenPharmacokinetics
Ulotaront oral
Oral doses studied 10-100 mg (dose-proportional PK); 25 mg single oral dose in the CYP2D6 healthy-subject study; once-daily dosing supported by PK.
OralOnce dailyt½ 7 h · Tmax 2 h

Mechanism of action (compound-wide)

Dual TAAR1 agonist / 5-HT1A agonist with no appreciable D2 or 5-HT2A activity.

TargetActionAffinity
TAAR1primaryTAAR1AgonistEC50 38 nM
5-HT1AHTR1AAgonistKi 284 nM

← Full SEP-363856 compound page (identity, identifiers, all indications)

Sources

  1. A Phase I, Open-Label, Fixed Sequence Study to Investigate the Effect of CYP2D6 Inhibition on the Pharmacokinetics of Ulotaront in Healthy Subjects — Clinical Pharmacokinetics (PMC)
  2. Sumitomo→Otsuka license amendment (ulotaront) — Sumitomo Pharma
  3. Ulotaront Phase 2/3 GAD (NCT05729373) — ClinicalTrials.gov
  4. Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia (synthesis/med-chem) — ACS Med Chem Lett (PMC)