PMID- 37165101
OWN - NLM
STAT- MEDLINE
DCOM- 20230831
LR  - 20230901
IS  - 1433-8491 (Electronic)
IS  - 0940-1334 (Print)
IS  - 0940-1334 (Linking)
VI  - 273
IP  - 7
DP  - 2023 Oct
TI  - Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 
      agonist in schizophrenia.
PG  - 1543-1556
LID - 10.1007/s00406-023-01580-3 [doi]
AB  - Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist in Phase 3 
      clinical development for the treatment of schizophrenia. Ulotaront was discovered 
      through a unique, target-agnostic approach optimized to identify drug candidates 
      lacking D2 and 5-HT2A receptor antagonism, while demonstrating an 
      antipsychotic-like phenotypic profile in vivo. The mechanism of action (MOA) of 
      ulotaront is thought to be mediated by agonism at TAAR1 and serotonin 5-HT1A 
      receptors. Ulotaront has completed two Phase 2 trials (4-week acute study and 
      26-week open-label extension) which led to Breakthrough Therapy Designation from 
      the US Food and Drug Administration for the treatment of schizophrenia. In the 
      double-blind, placebo-controlled, acute study, ulotaront was associated with 
      significant (p < 0.001) improvement in Positive and Negative Syndrome Scale 
      (PANSS) total score (effect size [ES]: 0.45), with improvements vs. placebo also 
      observed across secondary endpoints. Post-hoc analyses of the acute trial 
      revealed additional evidence to support the effect of ulotaront on negative 
      symptoms. In the 4-week study, ulotaront was well-tolerated, with an incidence of 
      adverse events (AEs) numerically lower compared to placebo (45.8% vs. 50.4%; with 
      a number needed to harm [NNH] for individual ulotaront AEs all > 40). The 
      open-label extension demonstrated further improvement across schizophrenia 
      symptoms and confirmed the tolerability of ulotaront, with a 6-month completion 
      rate of 67%. Based on current data, ulotaront shows potential to be a 
      first-in-class TAAR1 agonist for the treatment of schizophrenia with a safety and 
      efficacy profile distinct from current antipsychotics.
CI  - (c) 2023. The Author(s).
FAU - Achtyes, Eric D
AU  - Achtyes ED
AD  - WMU Homer Stryker M.D. School of Medicine, Kalamazoo, MI, USA.
FAU - Hopkins, Seth C
AU  - Hopkins SC
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
FAU - Dedic, Nina
AU  - Dedic N
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
FAU - Dworak, Heather
AU  - Dworak H
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
FAU - Zeni, Courtney
AU  - Zeni C
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. Courtney.Zeni@Sunovion.com.
FAU - Koblan, Kenneth
AU  - Koblan K
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230510
PL  - Germany
TA  - Eur Arch Psychiatry Clin Neurosci
JT  - European archives of psychiatry and clinical neuroscience
JID - 9103030
RN  - XMC8VP6RI2 (Trace amine-associated receptor 1)
RN  - 0 (SEP-363856)
RN  - 0 (Antipsychotic Agents)
SB  - IM
MH  - United States
MH  - Humans
MH  - *Schizophrenia/diagnosis
MH  - Treatment Outcome
MH  - *Antipsychotic Agents/adverse effects
MH  - Randomized Controlled Trials as Topic
PMC - PMC10465394
OTO - NOTNLM
OT  - Schizophrenia
OT  - Serotonin 5-HT1A
OT  - Trace amine-associated receptor 1
COIS- Dr. Achtyes has served on advisory boards or consulted for Alkermes, Atheneum, 
      Janssen, Karuna, Lundbeck/Otsuka, Roche, Sunovion and Teva. He has received 
      research support from Alkermes, Astellas, Biogen, Boehringer-Ingelheim, InnateVR, 
      Janssen, National Network of Depression Centers, Neurocrine Biosciences, 
      Novartis, Otsuka, Pear Therapeutics, and Takeda. He serves as an advisor to 
      CAPNOS Zero, the World Psychiatric Association and Clubhouse International, and 
      the SMI Adviser LAI Center of Excellence (all unpaid). Drs. Hopkins, Dedic, 
      Dworak, Zeni, and Koblan are employees of Sunovion Pharmaceuticals Inc.
EDAT- 2023/05/11 00:42
MHDA- 2023/08/31 06:42
PMCR- 2023/05/10
CRDT- 2023/05/10 23:23
PHST- 2023/01/18 00:00 [received]
PHST- 2023/02/26 00:00 [accepted]
PHST- 2023/08/31 06:42 [medline]
PHST- 2023/05/11 00:42 [pubmed]
PHST- 2023/05/10 23:23 [entrez]
PHST- 2023/05/10 00:00 [pmc-release]
AID - 10.1007/s00406-023-01580-3 [pii]
AID - 1580 [pii]
AID - 10.1007/s00406-023-01580-3 [doi]
PST - ppublish
SO  - Eur Arch Psychiatry Clin Neurosci. 2023 Oct;273(7):1543-1556. doi: 
      10.1007/s00406-023-01580-3. Epub 2023 May 10.